Longevity Papers

Alternative NADH dehydrogenase, also known as type II NADH dehydrogenase (NDH-2), catalyzes the same redox reaction as mitochondrial respiratory chain complex I. Specifically, it oxidizes reduced nicotinamide adenine dinucleotide (NADH) while simultaneously reducing ubiquinone to ubiquinol. However, unlike complex I, this enzyme is non-proton pumping, comprises of a single subunit, and is resistant to rotenone. Initially identified in bacteria, fungi and plants, NDH-2 was subsequently discovered in protists and certain animal taxa including sea squirts. The gene coding for NDH-2 is also present in the genomes of some annelids, tardigrades, and crustaceans. For over two decades, NDH-2 has been investigated as a potential substitute for defective complex I. In model organisms, NDH-2 has been shown to ameliorate a broad spectrum of conditions associated with complex I malfunction, including symptoms of Parkinson's disease. Recently, lifespan extension has been observed in animals expressing NDH-2 in a heterologous manner. A variety of mechanisms have been put forward by which NDH-2 may extend lifespan. Such mechanisms include the activation of pro-longevity pathways through modulation of the NAD

There is a growing need to better characterise senescent cells in the CNS and retina. The recently published SenMayo gene panel was developed to identify transcriptomic signatures of senescence across multiple organ systems, but the retina was not included. While other approaches have identified senescent signatures in the retina, these have largely focused on experimental models in young animals. We therefore conducted a detailed single-cell RNA-seq analysis to identify senescent cell populations in the retina of different aged mice and compared these with five comprehensive human and mouse retina and brain transcriptome datasets. Transcriptomic signatures of senescence were most apparent in mouse and human retinal glial cells, with IL4, 13 and 10 and the AP1 pathway being the most prominent markers involved. Similar levels of transcriptional senescence were observed in the retinal glia of young and old mice, whereas the human retina showed significantly increased enrichment scores with advancing age.

Unexplained stillbirth may occur due to premature placental ageing, with unexpected deterioration of placental function for gestational age. Circular RNAs (circRNAs) are enzyme-resistant RNA molecules that accumulate in ageing tissues. Furthermore, circRNAs bind gDNA directly, forming circRNA:DNA complexes which can induce DNA breaks. This study investigated circRNA accumulation with gestational age in healthy and stillbirth placentae and determined whether circRNAs directly interact with placental DNA causing DNA damage. Placenta samples (n=60 term uncomplicated; n=4 unexplained stillbirth) were assessed. Compared with earlier gestations (37, 38, 39, 40 weeks), placental DNA damage and expression of 6 candidate circRNAs (circ_0009000, circ_0024157, circ_0061017, circ_0036877, circ_0054624 and circ_0111277), but not their linear transcripts, were increased in 40 and 41+ weeks gestation samples, and in stillbirth. DRIP-qPCR signal size was significantly larger in term placentae than in enzyme-treated controls, confirming that all candidate circRNA loci bind to placental DNA. Depletion of circ_0009000 by specific siRNA in HEK293T cells, significantly reduced DNA damage compared to control, and increased expression of senescence-associated genes. Stillbirth placentae show accelerated ageing with premature accumulation of candidate circRNAs at levels consistent with older gestation tissue. These circRNAs bind to DNA and circ_0009000 causes DNA breaks and senescence in placenta. Therefore, circRNAs play a role in placental ageing and associate with stillbirth, likely via DNA damage. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/610398v3_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@64ad41org.highwire.dtl.DTLVardef@1aab2b6org.highwire.dtl.DTLVardef@1bb01f3org.highwire.dtl.DTLVardef@7d02a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

Prevalence and incidence of HIV among people aged 50 years and older continue to rise worldwide, generating increasing awareness among care providers, scientists, and the HIV community about the importance of brain health in older adults with HIV. Many age-related factors that adversely affect brain health can occur earlier and more often among people with HIV, including epigenetic ageing, chronic medical conditions (eg, cardiovascular disease), and age-related syndromes (eg, frailty). Extensive dialogue between HIV community leaders, health-care providers, and scientists has led to the development of a multidimensional response strategy to protect and enhance brain health in people ageing with HIV that spans across public health, clinical spaces, and research spaces. This response strategy was informed by integrated ageing care frameworks and is centred on prevention, early detection, and management of brain health issues associated with HIV (eg, neurocognitive disorders), with specific considerations for low-resource or middle-resource countries. A collaborative, international, and data-informed update of the diagnostic criteria for HIV-associated neurocognitive disorders is a cornerstone of the proposed response strategy. The proposed response strategy includes a dynamic, international, online knowledge hub that will provide a crucial community resource for emerging evidence on the brain health of people ageing with HIV.

As people live longer, maintaining brain health becomes essential for extending healthspan and preserving independence. Brain degeneration and cognitive decline are major contributors to disability. This study investigates how metabolic health influences brain-age-gap-estimate (brainAGE), which measures the difference between neuroimaging-predicted brain age and chronological age.

Assessing liver health and its determinants in the elderly is crucial. Lifestyle factors, including nutrition and exercise, may influence liver function. This study aimed to investigate the association between macronutrients and energy intake with serum levels of aminotransferases in elderly Iranian athletes and non-athletes.

Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells, and reversed SASP accumulation and SASP-mediated repressive interactions in human DP culture, resulting in an increased Wnt-active cell population. In hair reconstitution assays, senolytic-depleted DP cells exhibited restored hair inductive properties by regenerating de novo hair follicles (HFs) compared to untreated DP cells. In 3D skin constructs, senolytic-depleted DP cells enhanced inductive potential and hair lineage specific differentiation of keratinocytes. These data revealed that senolytic treatment of cultured human DP cells markedly increased their inductive potency in HF regeneration, providing a new rationale for clinical applications of senolytic treatment in combination with cell-based therapies.

While various lifestyle behaviors separately or partly have been shown to be associated with health outcomes, including a multitude of diseases and death, none of the earlier research has comprehensively investigated the combined impact of modified lifestyle behaviors. This longitudinal study investigated the association between a composite of healthy lifestyle behaviors and all-cause mortality in middle-aged and older Americans.

The fibrogenic conversion of satellite cells contributes to the atrophy and fibrosis of skeletal muscle, playing a significant role in the pathogenesis of age-related sarcopenia. Melatonin, a hormone secreted by the pineal gland, exhibits anti-aging and anti-fibrotic effects in various conditions. However, the effect of melatonin on satellite cell fate and age-related sarcopenia remains under-explored. Here, we report that melatonin treatment mitigated the loss of muscle mass and strength in aged mice, replenished the satellite cell pool and curtailed muscle fibrosis. When primary SCs were cultured in vitro and subjected to aging induction via D-galactose, they exhibited a diminished myogenic potential and a conversion from myogenic to fibrogenic lineage. Notably, melatonin treatment effectively restored the myogenic potential and inhibited this lineage conversion. Furthermore, melatonin attenuated the expression of the fibrogenic cytokine, transforming growth factor-β1, and reduced the phosphorylation of its downstream targets Smad2/3 both in vivo and in vitro. In summary, our findings show melatonin's capacity to counteract muscle decline and inhibit fibrogenic conversion in aging SCs and highlight its potential therapeutic value for age-related sarcopenia.

PurposeFunctional dependence is a multifactorial health condition affecting well-being and life expectancy. To better understand the mechanisms underlying this condition, we aimed to identify the variables that best prospectively classify adults with and without limitations in basic and instrumental activities of daily living. MethodsA filtering approach was used to select the best predictors of functional status from 4,248 candidate predictors collected in 39,927 participants aged 44 to 88 years old at baseline. Several machine learning models using the selected baseline variables (2010-2015) were compared for their ability to classify participants by functional status (dependent vs. independent) at follow up (2018-2021) on a training dataset (n=31,941) of participants from the Canadian Longitudinal Study on Aging. The best performing model was then examined on a test dataset (n=7,986) to confirm sensitivity, specificity, and accuracy. ResultsEighteen candidate baseline variables were identified as the best predictors of functional status at follow up. Logistic regression was the best performing model for classifying participants by functional status and achieved balanced accuracy of 81.9% on the test dataset. The absence of functional limitations at baseline, stronger grip strength, being free of pain and of chronic conditions, being a female, having a drivers license, and good memory were associated with greater odds functionally independence at follow-up. In contrast, older age, psychological distress, walking slowly, being retired, having one or more chronic conditions, and never going for walks were associated with greater odds of functional dependence at follow-up. ConclusionFunctional status can be best prospectively estimated by health condition, age, muscle strength, short-term memory, physical activity, psychological distress, and sex. These predictors can estimate functional status over 6 years ahead with high accuracy. This early identification of people at risk of functional dependence allows sufficient time for the implementation of interventions aiming to delay functional decline.

Metabolic syndrome could be a modifiable risk factor for dementia. However, the effects of age and duration of exposure to metabolic syndrome on dementia risk remains underexplored. The aim of this study was to determine whether the association between metabolic syndrome and risk of dementia differs across mid-life versus late-life, and to explore how duration of metabolic syndrome affects this risk.

Exposure to metals has been related to alterations in leukocyte telomere length (LTL), an aging marker. However, the evidence regarding this relationship in children and adolescents, as well as the underlying mechanisms, remains unclear. Therefore, we aimed to explore the individual and mixture effects of metals on LTL in children and adolescents and to assess the mediating role of thyroid hormones and the modifying effect of a healthy lifestyle. In a cross-sectional study performed in Liuzhou, China, we assessed 5 serum thyroid hormones, 18 urinary metals, and LTL among 1050 children and adolescents aged 6-18 years. We employed multivariate linear regression and weighted quantile sum (WQS) regression to assess the associations of urinary metals with LTL in children and adolescents. Mediation analyses were conducted to explore the effects of thyroid hormones on these relationships. Urinary cobalt (Co), nickel (Ni), strontium (Sr), mercury (Hg), cadmium (Cd), and thallium (Tl) were related to a shorter LTL in children and adolescents. The WQS regression showed a 6.31% (95% CI: -8.76%, -3.79%) decrease in LTL per quartile increase in the WQS index, and identified Ni (23.3%), Sr (21.7%), and Tl (18.0%) as the major contributors. Mediation analyses showed that triiodothyronine (T3) mediated 14.8% and 8.1% of the associations of urinary Sr and Hg with LTL, respectively, and suppressed 9.3% of the association with urinary Co. Furthermore, the inverse associations of Sr, Cd, and Tl with LTL were attenuated among participants who adopted a healthy lifestyle. Our findings suggested that exposure to Co, Ni, Sr, Cd, Hg, Tl, and their mixture were related to a shorter LTL in children and adolescents, potentially mediated by thyroid hormones. Additionally, adopting a healthy lifestyle may alleviate these adverse effects.

As the arrival of healthy aging, maintaining physical function (PF) in older adults is crucial for their health, so it is necessary to detect the decline of PF among them and take intervention measures.

The gut microbiota is closely related to aging, but the genetic relationship between gut microbiota and aging has not been well investigated. The aim of the study was to explore the association of microbiota with epigenetic age acceleration (EAA) using the Mendelian randomization.

Lysosomes are essential for neuronal homeostasis, providing degradation and recycling functions necessary to support neurons complex operations and long lifespans. However, the regulation of lysosomal degradative capacity in healthy neurons is poorly understood. Here, we investigate the role of HLH-30, the sole Caenorhabditis elegans homolog of Transcription Factor EB (TFEB), a master regulator of lysosome biogenesis and autophagy that it is thought to predominantly function in the context of starvation or stress. We demonstrate that HLH-30 is dispensable for neuronal development but acts cell-intrinsically to expand lysosomal degradative capacity during early adulthood. Loss of HLH-30 leads to lysosomal dysfunction and delayed turnover of synaptic vesicle proteins from the synapse. Notably, we show that basal HLH-30 activity is sufficient to expand neuronal lysosomal capacity without nuclear enrichment, in contrast to the nuclear translocation associated with starvation- and stress-induced activation of TFEB and HLH-30. Furthermore, we show that neuronal lysosomal function declines with age in wild-type animals, and this corresponds to a decrease in basal HLH-30-mediated transcription. We further demonstrate that basal HLH-30 activity is crucial for neuron maintenance: lysosomal dysfunction due to inadequate HLH-30 activity leads to dendrite degeneration and aberrant outgrowths. In summary, our study establishes a critical role for HLH-30/TFEB in promoting lysosomal capacity to preserve neuronal homeostasis and structural integrity of mature neurons in vivo.

Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition and signalling. While cellular aging is associated with functional changes across many cellular components contributing to the collective decline in cellular function, little is known about how it affects CME. Here we show that CME dynamics are significantly altered during replicative aging in budding yeast, with older cells having slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced cargo internalization. This change in CME dynamics is mother cell-specific and is not observed in daughter cells. We identified vacuolar pH, a key driver of aging phenotypes in budding yeast, as a central player in this modulation of CME dynamics during aging. Perturbing vacuolar pH in young cells mimics aging-like CME dynamics, while maintaining an acidic vacuolar pH in aging cells preserves CME dynamics typical of young cells. Finally, we demonstrate that the vacuolar pH effect on CME is regulated through TORC1 via the effector kinase Npr1. These findings establish vacuolar pH as a critical regulator of CME during cellular aging, and strengthen its role in the overall cellular aging process in budding yeast.

The global shift towards an aging population presents significant challenges, particularly concerning frailty among older adults. Frailty, characterized by diminished strength and resilience, increases vulnerability to diseases and hospitalization. Health Issues: Traditional diagnostic tools for frailty are costly and involve radiation risks, necessitating non-invasive, cost-effective methods like ultrasound. Frail older adults require intensive medical care, increasing healthcare costs and burdening systems. Scientific Challenges: Research must adopt a multidimensional approach, considering physical, psychological, and social factors of frailty. There is a pressing need to develop accessible diagnostic tools and translate research findings into clinical practice. Integrating ultrasound with machine learning enhances diagnostic accuracy and predictive capabilities, facilitating personalized care.

The objective of the study was to determine the specific roles of decorin and biglycan in the early and late phases of tendon healing in aged mice. Aged (300 day-old) female wildtype (WT), Dcn

Chondroitin extends lifespan and healthspan in C. elegans, but the relationship between extracellular chondroitin and intracellular anti-aging mechanisms is unknown. The basement membrane (BM) that contains chondroitin proteoglycans is anchored to cells via hemidesmosomes (HDs), and it accumulates damage with aging. In this study, we found that chondroitin regulates aging through the formation of HDs and inhibition of tubular lysosomes (TLs). Reduction of chondroitin due to a mutation in sqv-5/Chondroitin synthase (ChSy) causes the earlier and excessive formation of TLs and leakage of the lysosomal nuclease in a manner dependent on VHA-7, the a-subunit of V-type ATPase. VHA-7, whose mutation suppresses the short lifespan of the sqv-5 mutant, is initially localized to the basal side of the hypodermal cells and transported to lysosomes with aging. These results demonstrate that endogenous chondroitin suppresses aging by inhibiting the earlier excessive formation of TLs. This is a novel anti-aging mechanism that is controlled by the BM.

Excessive oxidative stress is known to cause endothelial dysfunction and drive cardiovascular diseases (CVD). While telomerase reverse transcriptase (TERT) shows protective effects against oxidative stress in rodents and is associated to human flow-mediated dilation in CVD, its regulatory mechanisms in human vascular systems under pathological oxidative stress require further investigation.

The Klotho gene is implicated in suppressing aging phenotypes and influencing age-related diseases. Previous studies have delved into its connection with different diseases, yet the association between Klotho and hearing loss has rarely been examined. A recent population study explored the relationship between serum Klotho and hearing loss, but it had certain limitations. This study aims to analyze the link between serum α-Klotho levels and hearing thresholds, as well as the risk of hearing loss.

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conduct a genetic meta-analysis of longevity in Diversity Outbred (DO) mice that includes 2,444 animals from three independently conducted lifespan studies. We identify six loci that contribute significantly to lifespan independently of diet and drug treatment, one of which also influences lifespan in a sex-dependent manner, as well as an additional locus with a diet-specific effect on lifespan. Collectively, these loci explain over half of the estimated heritable variation in lifespan across these studies and provide insight into the genetic architecture of lifespan in DO mice.

Skin autofluorescence (SAF), reflecting advanced glycation end-products' accumulation in tissue, has been proposed as a non-invasive aging biomarker. Yet, SAF has not been compared to well-established blood-based aging biomarkers such as MetaboHealth in association with frailty. Furthermore, no previous study determined the longitudinal association of SAF with frailty. We used 2382 Doetinchem Cohort Study participants' (aged 46.0 to 85.4) cross-sectional data, of whom 1654 had longitudinal SAF measurements. SAF was measured using the AGE reader™. MetaboHealth was calculated on 1H-NMR-metabolomics. Linear regressions were used for the associations of SAF and MetaboHealth on the 36-deficit frailty index and logistic regressions for being pre-frail or frail as determined by the frailty phenotype. Longitudinal associations were determined by an interaction term between age and SAF in a linear mixed model. SAF and MetaboHealth were associated with higher odds of pre-frailty (odd ratios per standard deviation SAF: 1.21(1.10;1.32), MetaboHealth: 1.35(1.24;1.49)) and frailty (SAF: 1.70(1.41;2.06), MetaboHealth: 1.90(1.57;2.32)). When mutually adjusted, both aging biomarkers remained associated with pre-frailty (SAF: 1.16(1.05;1.27), MetaboHealth 1.33(1.21;1.46)) and frailty (SAF: 1.52(1.25;1.85), MetaboHealth: 1.75(1.43;2.14)). Additionally, SAF and MetaboHealth were associated with higher frailty index scores (percentage increase per standard deviation SAF:1.35(1.00;1.70), MetaboHealth: 1.87(1.54;2.20)), also after mutual adjustment (SAF: 1.02(0.68;1.37), MetaboHealth: 1.69(1.35;2.02)). SAF was also longitudinally associated with the frailty index (percentage per unit/year increase 0.12(0.07;0.16)). The mutual independence of SAF and MetaboHealth implies they capture distinct aspects of the aging process. Altogether, these findings emphasize SAF's clinical potential as an age-related decline biomarker, which could be further enhanced when combined with MetaboHealth.

Innate host defense mechanisms require posttranslational modifications (PTM) to protect against viral infection. Age-associated immunosenescence results in increased pathogenesis and mortality in the elderly, but the contribution of altered PTM regulation to immunosenescence is unknown. SUMOylation is a rapid and reversible post-translational modification that has been implicated in age-associated disease and plays conflicting roles in viral replication and antiviral defenses in mammals. We have discovered in

Investigating the complexities of ageing through computational biology,

Primary age-related tauopathy (PART) and Alzheimers disease (AD) share hippocampal phospho-tau (p-tau) pathology but differ in p-tau extent and {beta}-amyloid presence. As a result, PART uniquely enables investigation of amyloid-independent p-tau mechanisms during brain aging. We conducted an epigenome-wide association (EWAS) study of PART, nominating 13 new and robust p-tau/methylation associations. We then jointly analyzed PART and AD epigenomes to develop novel epigenetic clocks, "TauAge", that predict p-tau severity in region-specific, age-, and {beta}-amyloid-independent manners. Integrative transcriptomic analyses revealed that genes involved in synaptic transmission are related to hippocampal p-tau severity in both PART and AD, while neuroinflammatory genes are related to frontal cortex p-tau severity in AD only. Further, a machine learning classifier trained on PART-vs-AD epigenetic differences stratifies an independent cohort of neuropathologically indeterminate cases into pathological subgroups with disparity in cognitive impairment. Together, these findings demonstrate the brain epigenomes substantial role in linking tau pathology to cognitive outcomes in aging and AD.

Studies using acute or subchronic pharmacological inhibition of phosphodiesterase 2 A (PDE2A) have led to its proposal as a target for treatment of cognitive deficits associated with neuropsychiatric and neurodegenerative disease. However, the impact of continuous inhibition of PDE2A on memory is unknown. Moreover, the neuroanatomical regions mediating memory enhancement have not been categorically identified. To address these open questions, we studied knockout mice and hippocampus restricted manipulations. Pde2a heterozygous knockout mice are viable with no gross histological abnormalities. The mice exhibit enhanced spatial and object recognition memory that is independent of anxiolytic effects and is paralleled by increased density of dendritic mushroom and thin spines in hippocampal CA3 and dentate gyrus in adult mice. In CA1, subtle alterations in spine density were seen, while theta-burst LTP and paired-pulse facilitation were normal. Spatial memory enhancement persists in aged Pde2a heterozygous knockout mice, and to our surprise these mice live significantly longer than wild-type littermate controls. In summary, we provide evidence that life-long reduction of PDE2A expression promotes spine formation and maturation, exerts beneficial effects on memory, and increases lifespan.

We present provocative data that in addition to the expected progressive age-related involution, mammary gland aging can occur in a cyclical pattern and is dictated by maternal ancestry. In cyclical aging, mammary glands of 11 and 19 months old mice share genetic and proteomic signatures, which are enriched in breast cancer-related pathways, but are absent at 3 and 14 months. Since incidence of breast cancer shows a bimodal age distribution at 45 (~11m in mice) and 65 (~ 19m in mice), cyclical aging may contribute to these peaks of cancer susceptibility. Conversely, since the mammary glands at 3 and 14 months cluster together hierarchically, the cancer-associated peaks seem separated by a rejuvenation phase. Since cyclical aging is observed in mice with extended lifespan, these findings raise the possibility that if oncogenic mutations are avoided during the pro-oncogenic phases, through its rejuvenation phase, cyclical aging may impact multiple organs leading to extended longevity.

Mitochondrial calcium (mtCa

Healthy aging often entails a decline in cognitive and motor functions, affecting independence and quality of life in older adults. Brain stimulation shows potential to enhance these functions, but studies show variable effects. Previous studies have tried to identify responders and non-responders through correlations between behavioral change and baseline parameters, but results lack generalization to independent cohorts. We propose a method to predict an individual's likelihood of benefiting from stimulation, based on baseline performance of a sequential motor task. Our results show that individuals with less efficient learning mechanisms benefit from stimulation, while those with optimal learning strategies experience none or even detrimental effects. This differential effect, first identified in a public dataset and replicated here in an independent cohort, was linked to one's ability to integrate task-relevant information and not age. This study constitutes a further step towards personalized clinical-translational interventions based on brain stimulation.

Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related retinal changes. To address this, we used a genetic model of systemic depletion of expression of the DNA repair enzyme ERCC1-XPF. The neural retina and retinal pigment epithelium (RPE) from Ercc1

Substantial evidence from epidemiological and clinical studies suggests that exposure to stress during sensitive developmental periods strongly and robustly increases the risk for psychiatric and physical disorders, resulting in reduced longevity. Chronic immune activation has been proposed as one mechanism through which early adverse experiences may become biologically embedded. This paper highlights selected key findings and questions that first emerged in the literature and founded the field and then examines how research methods and questions have evolved over time.

With a growing elderly population in the European Union, age-related diseases associated with unhealthy aging pose increasing public health challenges, including a loss of independence and heightened societal burdens. The Semmelweis Study, a prospective occupational cohort study in Hungary, seeks to identify determinants of unhealthy aging, focusing on the complex relationship between lifestyle, environmental, occupational factors, and the development of chronic age-associated diseases, including age-related vascular cognitive impairment (VCI). The primary objective of this pilot study was to establish a robust, high-throughput assessment methodology to comprehensively evaluate both peripheral and cerebrovascular health to provide a solid foundation for the forthcoming Semmelweis Study framework. The study involved 49 participants aged 23 to 87 years, and it assessed multi-domain cognitive performance through an automated battery of tests (CANTAB). Vascular health was comprehensively evaluated using laser speckle contrast imaging (LSCI), flow-mediated dilation (FMD), static and dynamic retinal vessel analysis (SVA, DVA), and measurements of vascular stiffness. The retinal microvasculature, which closely mirrors the cerebral circulation in anatomy, physiology, and pathophysiology, provided a unique window for examination. Optical imaging through SVA and DVA enables the identification of structural and functional changes in the central nervous system's microcirculation, which are highly relevant to the pathogenesis of VCI. Subsequently, the collected measures were integrated into vascular health indices using principal component analysis (PCA) and the relationship to the age and cognitive status of study participants was explored. These comprehensive vascular health indices demonstrated a correlation not only with age but also with cognitive performance. This methodology holds promise for providing novel insights into the intricate interplay between vascular and cognitive health within the context of the Semmelweis Study.

Introduction The pathogenesis of aging nephropathy is yet to be elucidated. Intrarenal Angiotensin-II (AngII) and activation of the NF-κB and NLRP3 inflammasome pathways exert a relevant pathogenic role in the progression of chronic kidney disease (CKD). We sought to investigate whether monotherapy with Losartan and combined treatment with Losartan and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) would attenuate experimental aging nephropathy. Materials and Methods Forty adult Male Munich-Wistar rats were distributed among four groups: 12M (n=10), untreated 12-month-old rats; 15M (n=10), untreated 15-month-old rats; 15MLos (n=8), rats receiving Losartan (50 mg/kg/d) and 15MLos+PDTC (n=8), rats receiving Losartan and PDTC (60 mg/kg/d). All treatments were given by mouth from 12 to 15 months of age. Results Group 15M exhibited slightly decreased tail-cuff pressure, and marked increase in albuminuria, sclerotic glomeruli, cortical collagen-1 deposition and infiltration by myofibroblasts, AngII-positive cells and proinflammatory M1 macrophages, whereas the amount of anti-inflammatory M2 macrophages was reduced. In addition, the renal abundance of TLR4, nuclear p65 and IL-6 was increased, indicating activation of the NF-κB pathway, without evidence of simultaneous activation of the NLRP3 cascade. Losartan treatment decreased cortical collagen-1 deposition, myofibroblasts and AngII-positive cells, and partially restored renal M2, but had no significant effect on albuminuria, glomerulosclerosis or NF-κB activation. Combined Losartan+PDTC prevented all the observed abnormalities. Discussion/conclusion Simultaneous blockade of renal AngII and inhibition of the NF-κB pathway may represent a novel alternative to limit the decline of renal function with age.

Meditation is a mental training approach that can improve mental health and well-being in aging. Yet the underlying mechanisms remain unknown. The Medit-Ageing model stipulates that three mechanisms - attentional, constructive, and deconstructive - upregulate positive psycho-affective factors and downregulate negative ones. To test this hypothesis, we measured brain structural MRI and perfusion, negative and positive psycho-affective composite scores, and meditation mechanisms in 27 older expert meditators and 135 meditation-naive older controls. We identified brain and psycho-affective differences and performed mediation analyses to assess whether and which meditation mechanisms mediate their links.Meditators showed significantly higher volume in fronto-parietal areas and perfusion in temporo-occipito-parietal areas. They also had higher positive and lower negative psycho-affective scores. Attentional and constructive mechanisms both mediated the links between brain differences and the positive psycho-affective score whereas the deconstructive mechanism mediated the links between brain differences and the negative psycho-affective score.Our results corroborate the Medit-Ageing model, indicating that, in aging, meditation leads to brain changes that decrease negative psycho-affective factors and increase positive ones through relatively specific mechanisms. Shedding light on the neurobiological and psycho-affective mechanisms of meditation in aging, these findings provide insights to refine future interventions.

Aging increases the risk of a myriad of chronic diseases, which are expensive and difficult to treat owing to their various risk factors. Repurposing existing anti-aging medications has accelerated the development of therapies aimed at slowing aging. In this study, we revealed that enalapril, a drug widely prescribed for hypertension, can improve both cellular senescence and individual health. Mechanistically, phosphorylated Smad1/5/9 act as pivotal mediators of the anti-aging properties of enalapril. It stimulates downstream genes involved in cell cycle regulation and antioxidative defense, facilitating cell proliferation and diminishing the production of reactive oxygen species (ROS), thus increasing the antioxidative ability of enalapril. At the organismal level, enalapril has been shown to bolster the physiological performance of various organs; it notably enhances memory capacity and renal function and relieves lipid accumulation. Our work highlights the potential of enalapril to augment antioxidant defenses and combat the effects of aging, thereby indicating its promise as a treatment strategy for aging-associated diseases and its use for healthy aging.

Aging involves a progressive deterioration in physiological functions and increased disease susceptibility, impacting all organs and tissues, especially the skin. Skin aging is driven by intrinsic factors (genetics, cellular metabolism) and extrinsic factors (environment, lifestyle). Understanding these mechanisms is vital for promoting healthy aging and mitigating skin aging effects. This review aims to summarize the key factors influencing skin and intrinsic aging, providing a comprehensive understanding of the underlying mechanisms and contributing elements.

Age-related alterations of the immune system compromise the host's ability to respond to pathogens, but how immune aging is regulated is still poorly understood. Here, we identify via transcriptomic analysis of splenic DCs and bone marrow derived dendritic cells (BMDC) of young and aged mice, the small GTPase Rab8a as a regulator of dendritic cell (DC) functions in mice. CD11c

Early life adversity has been shown to have long-lasting detrimental effects on a variety of biopsychosocial outcomes. Early adversity and its consequences may directly or indirectly affect cognitive aging and increase the risk of developing dementia in older age. Investigating the biopsychosocial outcomes associated with early adverse experiences is essential to inform health policies and promote healthy cognitive development across the life course.

Hematopoietic stem cells (HSCs) responsible for blood cell production and their bone marrow regulatory niches undergo age-related changes, impacting immune responses and predisposing individuals to hematologic malignancies. Here, we show that the age-related alterations of the megakaryocytic niche and associated downregulation of Platelet Factor 4 (PF4) are pivotal mechanisms driving HSC aging. PF4-deficient mice display several phenotypes reminiscent of accelerated HSC aging, including lymphopenia, increased myeloid output, and DNA damage, mimicking physiologically aged HSCs. Remarkably, recombinant PF4 administration restored old HSCs to youthful functional phenotypes characterized by improved cell polarity, reduced DNA damage, enhanced in vivo reconstitution capacity, and balanced lineage output. Mechanistically, we identified LDLR and CXCR3 as the HSC receptors transmitting the PF4 signal, with double knockout mice showing exacerbated HSC aging phenotypes similar to PF4-deficient mice. Furthermore, human HSCs across various age groups also respond to the youthful PF4 signaling, highlighting its potential for rejuvenating aged hematopoietic systems. These findings pave the way for targeted therapies aimed at reversing age-related HSC decline with potential implications in the prevention or improvement of the course of age-related hematopoietic diseases. Key PointsO_LIAge-related attrition of the megakaryocytic niche and associated PF4 downregulation is a central mechanism in HSC aging. C_LIO_LIPF4 supplementation, acting on LDLR and CXCR3 receptors, rejuvenates the function of aged HSCs. C_LI

Autophagy maintains the stability of eukaryotic cells by degrading unwanted components and recycling nutrients and plays a pivotal role in muscle regeneration by regulating the quiescence, activation, and differentiation of satellite cells. Effective muscle regeneration is vital for maintaining muscle health and homeostasis. However, under certain disease conditions, such as aging, muscle regeneration can fail due to dysfunctional satellite cells. Dysregulated autophagy may limit satellite cell self-renewal, hinder differentiation, and increase susceptibility to apoptosis, thereby impeding muscle regeneration. This review explores the critical role of autophagy in muscle regeneration, emphasizing its interplay with apoptosis and recent advances in autophagy research related to diseases characterized by impaired muscle regeneration. Additionally, we discuss new approaches involving autophagy regulation to promote macrophage polarization, enhancing muscle regeneration. We suggest that utilizing cell therapy and biomaterials to modulate autophagy could be a promising strategy for supporting muscle regeneration. We hope that this review will provide new insights into the treatment of muscle diseases and promote muscle regeneration.

Aging has profound effects on the body, most notably an increase in the prevalence of several diseases. An important aging hallmark is the presence of senescent cells that no longer multiply nor die off properly. Another characteristic is an altered immune system that fails to properly self-surveil. In this multi-player aging process, cellular senescence induces a change in the secretory phenotype, known as senescence-associated secretory phenotype (SASP), of many cells with the intention of recruiting immune cells to accelerate the clearance of these damaged senescent cells. However, the SASP phenotype results in inducing secondary senescence of nearby cells, resulting in those cells becoming senescent, and improper immune activation resulting in a state of chronic inflammation, called inflammaging, in many diseases. Senescence in immune cells, termed immunosenescence, results in further dysregulation of the immune system. An interdisciplinary approach is needed to physiologically assess aging changes of the immune system at the cellular and tissue level. Thus, the intersection of biomaterials, microfluidics, and spatial omics has great potential to collectively model aging and immunosenescence. Each of these approaches mimics unique aspects of the body undergoes as a part of aging. This perspective highlights the key aspects of how biomaterials provide non-cellular cues to cell aging, microfluidics recapitulate flow-induced and multi-cellular dynamics, and spatial omics analyses dissect the coordination of several biomarkers of senescence as a function of cell interactions in distinct tissue environments. An overview of how senescence and immune dysregulation play a role in organ aging, cancer, wound healing, Alzheimer's, and osteoporosis is included. To illuminate the societal impact of aging, an increasing trend in anti-senescence and anti-aging interventions, including pharmacological interventions, medical procedures, and lifestyle changes is discussed, including further context of senescence.

The genus Myotis is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated near-complete genome assemblies and cell lines for 8 closely related species of Myotis. Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cell lines, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats. We find that Myotis bats have some of the most significant variation in cancer risk across mammals and demonstrate a unique DNA damage response in primary cells of the long-lived M. lucifugus. We also find evidence of abundant adaptation in response to DNA viruses - but not RNA viruses - in Myotis and other bats in sharp contrast with other mammals, potentially contributing to the role of bats as reservoirs of zoonoses. Together, our results demonstrate how genomics and primary cells derived from diverse taxa uncover the molecular bases of extreme adaptations in non-model organisms.

The intricate relationship between hydrogen sulfide (H

Exfoliation Syndrome (XFS) is an age-related systemic condition characterized by large aggregated fibrillar material deposition in the anterior eye tissues. This aggregate formation and deposition on the aqueous humor outflow pathway are significant risk factors for developing Exfoliation Glaucoma (XFG), a secondary open-angle glaucoma. XFG is a complex, multifactorial late-onset disease that shares common features of neurodegenerative diseases, such as altered cellular processes with increased protein aggregation, impaired protein degradation, and oxidative and cellular stress. XFG patients display decreased mitochondrial membrane potential and mitochondrial DNA deletions. Here, using Tenon Capsule Fibroblasts (TFs) from Normal (No Glaucoma) and XFG patients, we found that XFG TFs have impaired mitochondrial bioenergetics and increased reactive oxygen species (ROS) accumulation. These defects are associated with mitochondrial abnormalities as XFG TFs exhibit smaller mitochondria that contain dysmorphic cristae, with an increase in mitochondrial localization to lysosomes and slowed mitophagy flux. Mitochondrial dysfunction in the XFG TFs was associated with an increase in the dynamics of the microtubule cytoskeleton, decreased acetylated tubulin, and increased HDAC6 activity. Treatment of XFG TFs with a mitophagy inducer, Urolithin A, and a mitochondrial biogenesis inducer, NAD+ precursor, Nicotinamide Ribose, improved mitochondrial bioenergetics and reduced ROS accumulation. Our results demonstrate abnormal mitochondria in XFG TFs and suggest that mitophagy inducers may represent a potential class of therapeutics for reversing mitochondrial dysfunction in XFG patients.

The distribution of biomolecules within cells changes upon aging and diseases. To quantitatively determine the spatial distribution of components inside cells, we built the user-friendly open-source 3D-cell-image analysis platform Cell Detection and Analysis of Intensity Lounge (CellDetail). The algorithm within CellDetail is based on the concept of the dipole moment. CellDetail provides quantitative values for the distribution of the polarity proteins Cdc42 and Tubulin in young and aged hematopoietic stem cells (HSCs). Septin proteins form networks within cells that are critical for cell compartmentalization. We uncover a reduced level of organization of the Septin network within aged HSCs and within senescent human fibroblasts. Changes in the Septin network structure might therefore be a common feature of aging. The level of organization of the network of Septin proteins in aged HSCs can be restored to a youthful level by pharmacological attenuation of the activity of the small RhoGTPase Cdc42.

Experimental evolution studies that feature selection on life-history characters are a proven approach for studying the evolution of aging and variation in rates of senescence. Recently, the incorporation of genomic and transcriptomic approaches into this framework has led to the identification of hundreds of genes associated with different aging patterns. However, our understanding of the specific molecular mechanisms underlying these aging patterns remains limited. Here, we incorporated extensive metabolomic profiling into this framework to generate mechanistic insights into aging patterns in Drosophila melanogaster. Specifically, we characterized metabolomic change over adult lifespan in populations of D. melanogaster where selection for early reproduction has led to an accelerated aging phenotype relative to their controls. Using these data we: i) evaluated evolutionary repeatability across the metabolome; ii) assessed the value of the metabolome as a predictor of "biological age" in this system; and iii) identified specific metabolites associated with accelerated aging. Generally, our findings suggest that selection for early reproduction resulted in highly repeatable alterations to the metabolome and the metabolome itself is a reliable predictor of "biological age". Specifically, we find clusters of metabolites that are associated with the different rates of senescence observed between our accelerated aging population and their controls, adding new insights into the metabolites that may be driving the accelerated aging phenotype. SignificanceWhile experimental evolution studies featuring Drosophila melanogaster have generated significant insights into the forces that shape aging and life history patterns, more recent efforts incorporating genomic and transcriptomic data have had comparatively little success identifying the molecular mechanisms underlying these patterns. Here we work to incorporate molecular phenotyping into this general framework as a way forward. Specifically, we characterize how the metabolome changes with age in populations of D. melanogaster where hundreds of generations of selection for early reproduction have led to enrichment for an accelerated aging phenotype. By comparing to control populations, we show that the metabolome does appear to capture true signals of "biological age" and provides a new avenue for understanding the factors that underlie complex trait variation in real populations.

Polyamines are bioactive amines found in almost all living organisms and are essential for normal cellular functions [...].

Telomere length function serves as a critical biomarker for biological aging and overall health. Its maintenance is linked to cancer, neurodegenerative conditions, and reproductive health. This review mainly examines genetic variations and environmental influences on telomere dynamics, highlighting key regulatory genes and mechanisms. Advances in telomere measurement methodologies are also reviewed, underscoring the importance of precise telomere assessment for disease prevention and treatment. Telomerase activation offers potential for cellular lifespan extension and anti-aging effects, whereas its inhibition emerges as a promising therapeutic approach for cancer. Regulatory mechanisms of tumor suppressor genes on telomerase activity are analyzed, with a comprehensive overview of the current state and future potential of telomerase inhibitors. In addition, the association between telomeres and neurodegenerative diseases is discussed, detailing how telomere attrition heightens disease risk and outlining multiple pathways by which telomerase protects neurons from damage and apoptosis.

Although there are multiple high-performing epigenetic aging clocks, few aging clocks based on gene expression exist, which allow direct prediction of age-associated genes. Existing transcriptomic clocks exhibit inconsistent performance and are limited in their ability to predict novel biomarkers. With the growing popularity of single-cell sequencing, there is a need for robust single-cell transcriptomic aging clocks. Moreover, clocks have yet to be applied to investigate the elusive phenomenon of sex differences in aging. We introduce TimeFlies, a pan-cell-type scRNA-seq aging clock for the Drosophila melanogaster head. TimeFlies uses interpretable deep learning to classify donor age of cells based on gene expression. We identified key marker genes used in classification; lncRNAs were highly enriched among predicted biomarkers. The top biomarker gene across cell types is lncRNA:roX1, a regulator of X chromosome dosage compensation, a pathway previously identified as a top biomarker of aging in the mouse brain. We validated this finding experimentally, showing a decrease in survival probability in the absence of roX1 in vivo. Furthermore, we trained sex-specific TimeFlies clocks and noted significant differences in model predictions and explanations between male and female clocks, suggesting that different pathways drive aging in males and females. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/625273v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@586c18org.highwire.dtl.DTLVardef@120b36dorg.highwire.dtl.DTLVardef@1e3d147org.highwire.dtl.DTLVardef@1c0926a_HPS_FORMAT_FIGEXP M_FIG C_FIG

Evidence suggests that polyphenol-rich foods like berries may help counteract aging-related disorders such as vascular dysfunction and arterial stiffness. However, few intervention studies have been conducted in older adults. This study aimed to assess whether the consumption of blueberries may improve vascular function in older subjects. A randomized, controlled, crossover trial was conducted in a group of 20 volunteers over 60 years old. Participants consumed either a blueberry mousse (250 g, providing 480 mg of anthocyanins - ACNs) or a control product (250 mL of sugared water), with treatments separated by at least 1-week. Reactive hyperemia index (RHI), augmentation index (AIx), blood pressure, and heart rate were measured at baseline and 2 h post-consumption. Blood samples were collected at baseline and after 1, 1.5, 2 and 4 h from the intake to evaluate ACN bioavailability, metabolic, and vascular markers. Sixteen subjects completed the trial (9 males, 7 females; mean age 69 ± 5 years). Blueberry consumption significantly increased RHI compared to control (mean difference + 0.42, 95 % CI: 0.01-0.082, p < 0.05). Maximum serum ACN concentration was observed at 2 h (20.3 ± 7.4 ng/mL). No association was found between RHI improvement and total serum ACNs, but a significant positive correlation was detected with delphinidin and cyanidin-3-glucoside (p < 0.01). No effects on AIx, blood pressure, or other markers were found. In conclusion, blueberries may improve peripheral vascular function in older adults, potentially due to increased ACN levels. Further studies are needed to corroborate these findings and elucidate the mechanisms involved.

Oxidative stress is closely linked to aging. Probiotics, whether viable or heat-inactivated, have shown antioxidant properties; however, their effect and mechanism of action in reducing oxidative stress during aging remains underexplored. This study examined the effects of viable and heat-inactivated

Insulin resistance, stem cell dysfunction, and muscle fiber dystrophy are all age-related events in skeletal muscle (SKM). However, age-related changes in insulin isoforms and insulin receptors in myogenic progenitor satellite cells have not been studied. Since SKM is an extra-pancreatic tissue that does not express mature insulin, we investigated the levels of insulin receptors (INSRs) and a novel human insulin upstream open reading frame (INSU) at the mRNA, protein, and anatomical levels in Baltimore Longitudinal Study of Aging (BLSA) biopsied SKM samples of 27-89-year-old (yrs) participants. Using RT-qPCR and the MS-based selected reaction monitoring (SRM) assay, we found that the levels of INSR and INSU mRNAs and the proteins were positively correlated with the age of human SKM biopsies. We applied RNAscope fluorescence in situ hybridization (FISH) and immunofluorescence (IF) to SKM cryosections and found that INSR and INSU were co-localized with PAX7-labeled satellite cells, with enhanced expression in SKM sections from an 89 yrs old compared to a 27 yrs old. We hypothesized that the SKM aging process might induce compensatory upregulation of INSR and re-expression of INSU, which might be beneficial in early embryogenesis and have deleterious effects on proliferative and myogenic satellite cells with advanced age.

Cellular senescence is a state of permanent cell cycle arrest and plays an important role in many vascular lesions. This study found that the cells of diabetic patients have more characteristics of senescence, which may cause microvascular complications. Cell senescence, as one of the common fates of cells, links microangiopathy and diabetes. Cell senescence in a high-glucose environment can partially elucidate the mechanism of diabetic microangiopathy, and various types of cellular senescence induced by it can promote the progression of diabetic microangiopathy. Still, the molecular mechanism of microangiopathy-related cellular senescence has not yet been clearly studied. Building on recent research evidence, we herein summarize the fundamental mechanisms underlying the development of cellular senescence in various microangiopathies associated with diabetes. We gradually explain how cellular senescence serves as a key driver of diabetic microangiopathy. At the same time, the treatment of basic senescence mechanisms such as cellular senescence may have a great impact on the pathogenesis of the disease, may be more effective in preventing the development of diabetic microangiopathy, and may provide new ideas for the clinical treatment and prognosis of diabetic microangiopathy.

There is evidence of the effect of probiotic intake on the immune system. However, the effect probiotics may have on the rate of aging is unknown. The aim of this study is to determine the effect of a probiotic blend on immunity, redox state, inflammation, and the rate of aging or biological age. A group of 10 men and 14 women took, daily for 2 months, a sachet with three probiotics (

The demographic transition has become a reality, and it demands public policies to promote physical and mental health in aging. Group exercise emerges as a cost-effective and accessible alternative to promote active aging on a large scale, but to optimize the effectiveness of these programs, it is crucial to understand the underlying mechanisms that improve quality of life. This study aimed to explore the associations between emotional status, cognitive functioning, motor dysfunction, and their relationship with quality of life in community-dwelling older adults participating in a group physical exercise program. Structural equation modeling was used to explore these relationships in a sample of 190 older adults. Emotional state directly predicted all domains of quality of life. Motor dysfunction predicts the physical health domain of quality of life. Motor dysfunction and cognitive functioning are strongly correlated with emotional status. The fit indices of the final model are acceptable, and it demonstrates that within group-exercise dynamics, emotional status is the main component of quality-of-life promotion. Therefore, professionals designing group physical exercise programs to promote active aging should consider not only physical fitness, but also the integration of psychosocial elements, offering a holistic approach to enhancing overall well-being.

Cardiovascular disease (CVD) is the predominant cause of mortality, with aging being a significant risk factor. Nucleotides (NTs), essential for numerous biological functions, are particularly vital under conditions like aging, starvation, and nutrient deficiency. Although the antiaging benefits of exogenous NTs have been recognized in various systems, their cardiac-specific effects are not well understood. This study, therefore, investigated the impact of exogenous NTs on cardiac aging and delved into the potential mechanisms.

The rate of aging can be determined, among other factors, by the diet during childhood and adolescence. Many additives are currently added to food, including carrageenan (E-407), a thickener derived from red algae. Although the acceptable daily intake for carrageenan is periodically re-evaluated, children show the highest levels of exposure with unknown potential effects on the aging process and longevity. Therefore, the aim of the present study is to know the effects in young mice of carrageenan intake, at the maximum level exposure scenario surveyed in children, on the homeostatic (nervous and immune) systems, the redox-inflammatory state and the repercussion that this may have on the aging and longevity of the animals. Swiss mice of 2 months of age (equivalent to 8 years old children) were used and 4 experimental groups were created (N = 10 animals/group): females and males that ingested carrageenan (540 mg/kg of κ-carrageenan in 200 μL of drinking water by pipette tip administration) and control females and males that took 200 μL of water, daily for 15 days. After that time, a battery of behavioral tests was performed, and peritoneal leukocytes were extracted to assess different immune functions and their redox and inflammatory state. These tests were repeated when the mice reached adulthood (7 months) and old age (18 months). Fecal microbiota was analyzed at the same sampling times. The results showed that animals that ingested carrageenan presented elevated levels of anxiety, impaired immune function and increased oxidative-inflammatory stress, with these effects extending into adulthood and old age and leading to reduced longevity in these mice. Overall, observed microbiota changes were related more to the aging process than the carrageenan intake. In conclusion, the exposure to high doses of the food additive carrageenan in childhood may contribute to an impairment of homeostasis, and consequently of health, with an increased oxidative-inflammatory stress, which implies an accelerated aging process, leading to a lower longevity.

Aging is the result of a complex interplay of physical, environmental, and social factors, leading to an increased prevalence of chronic age-related diseases that burden health and social care systems. As the global population ages, it is crucial to understand the aged immune system, which undergoes declines in both innate and adaptive immunity. This immune decline exacerbates the aging process, creating a feedback loop that accelerates the onset of diseases, including infectious diseases, autoimmune disorders, and cancer. Intervention strategies, including dietary adjustments, pharmacological treatments, and immunomodulatory therapies, represent promising approaches to counteract immunosenescence. These interventions aim to enhance immune function by improving the activity and interactions of aging-affected immune cells, or by modulating inflammatory responses through the suppression of excessive cytokine secretion and inflammatory pathway activation. Such strategies have the potential to restore immune homeostasis and mitigate age-related inflammation, thus reducing the risk of chronic diseases linked to aging. In summary, this review provides insights into the effects and underlying mechanisms of immunosenescence, as well as its potential interventions, with particular emphasis on the relationship between aging, immunity, and nutritional factors.

The prevalence and severity of gastrointestinal diseases were increased with age. In this study, the intestinal protective effects of Lactococcus lactis HF08 (HF08) and its derived postbiotic (P-HF08) on D-gal-induced aging mice and D-gal/DSS-induced aging colitis mice were investigated. In D-gal-induced aging mice, both HF08 and P-HF08 alleviated aging-related intestinal barrier dysfunction, inflammatory status, and gut microbiota disorder. The effects of probiotic HF08 were superior to those of postbiotic P-HF08, attributed to ability of HF08 to regulate the gut microbiota. However, in D-gal/DSS-induced aging colitis mice, the effects of P-HF08 on colitis surpassed that of HF08. Specifically, both HF08 and P-HF08 could reduce symptoms of age-related colitis, including reduction of lose weight, the DAI score, colonic shortening, and colon tissue damage. The inhibitory effects of P-HF08 on intestinal inflammation surpassed those of HF08, as evidenced by the levels of colon IL-6, IL-1β, and IL-10. Western blot results demonstrated that the anti-inflammatory effects of P-HF08 were attributed to the downregulation of key proteins in the TLR4/NF-κB pathway. And four potential TLR4 inhibitors were identified from HF08 metabolites (eplerenone, genistein, indoleacrylic acid, and turanose) by molecular docking. Nevertheless, HF08 could better regulate gut microbiota and metabolite in aging-related colitis than P-HF08, which was consistent with the results on aging mice. Overall, our finding revealed that when the intestinal barrier was intact (aging), probiotics showed superior regulation of intestinal microbiota, while postbiotics offered greater safety in case of intestinal barrier damage (aging colitis). This study offered a novel perspective into the applications of probiotics and their derivatives in the aging related gastrointestinal diseases adjuvant therapy.

Accumulation of senescent endothelial cells (ECs) in vasculature represents a key step in the development of vascular aging and ensuing age-related diseases. Given that removal of senescent ECs may prevent disease and improve health and wellbeing, the discovery of novel biomarkers that effectively identify senescent cells is of particular importance. As crucial elements for biological pathways and reliable bioindicators of cellular processes, metabolites demand attention in this context. Using senescent human brain microvascular endothelial cells (HBMECs) displaying a secretory phenotype and significant morphological, nuclear, and enzymatic changes compared to their young counterparts, this study has shown that senescent HBMECs lose their endothelial characteristics as evidenced by the disappearance of CD31/PECAM-1 from interendothelial cell junctions. The metabolic profiling of young versus senescent HBMECs also indicates significant differences in glucose, glutamine, and fatty acid metabolism. The analysis of intracellular and secreted metabolites proposes L-proline, L-glutamate, NAD

Organoids have emerged as transformative tools in biomedical research, renowned for their ability to replicate the complexity construct of human tissues. Skin aging is a multifaceted biological process, influenced by both intrinsic factors and extrinsic factors. Traditional models for studying skin aging often fall short in capturing the intricate dynamics of human skin. In contrast, skin organoids offer a more physiologically relevant system, reflecting the structural and functional characteristics of native skin. These characteristics make skin organoids highly suitable for studying the mechanisms of skin aging, identifying novel therapeutic targets, and testing anti-aging interventions. Despite their promise, challenges such as limited scalability, reproducibility, and ethical considerations remain. Addressing these hurdles through interdisciplinary research and technological advancements will be essential to maximizing the potential of skin organoids for dermatological research and personalized anti-aging therapies.

Oxidative stress plays a crucial role in mediating life-history processes, where it can compromise survival and reproduction through harmful alterations to DNA, lipids, and proteins. In this study, we investigated oxidative stress in Cape ground squirrels (

Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions.

Vitamin E (Vit E) deficiency studies underline the relevance of this vitamin in skeletal muscle (SkM) homeostasis. The knowledge of the effectors and modulators of Vit E action in SkM cells is limited, especially in aging and chronic diseases characterized by a decline in musculoskeletal health. Vit E comprises eight fat-soluble compounds grouped into tocopherols and tocotrienols, which share the basic chemical structure but show different biological properties and potentials to prevent diseases. Vit E has antioxidant and non-antioxidant activities and both favorable and adverse effects depending on the specific conditions and tissues. In this review, we focus on the actual knowledge of Vit E forms in SkM functions and new potential signaling effectors (i.e., bioactive sphingolipids and myokines). The possible advantages of Vit E supplementation in counteracting SkM dysfunctions in sarcopenia and under microgravity will also be discussed.

The lifestyle patterns of top athletes are highly disciplined, featuring strict exercise regimens, nutrition plans, and mental preparation, often beginning at a young age. Recently, it was shown that physically active individuals exhibit slowed epigenetic aging and better age-related outcomes. Here, we investigate whether the extreme intensity of physical activity of Olympic champions still has a beneficial effect on epigenetic aging. To test this hypothesis, we examined the epigenetic aging of 59 Hungarian Olympic champions and of the 332 control subjects, 205 were master rowers. We observed that Olympic champions exhibit slower epigenetic aging, applying seven state-of-the-art epigenetic aging clocks. Additionally, male champions who won any medal within the last 10 years showed slower epigenetic aging compared to other male champions, while female champions exhibited the opposite trend. We also found that wrestlers had higher age acceleration compared to gymnasts, fencers, and water polo players. We identified the top 20 genes that showed the most remarkable difference in promoter methylation between Olympic champions and non-champions. The hypo-methylated genes are involved in synaptic health, glycosylation, metal ion membrane transfer, and force generation. Most of the hyper-methylated genes were associated with cancer promotion. The data suggest that rigorous and long-term exercise from adolescence to adulthood has beneficial effects on epigenetic aging.

Aging constitutes complex and dynamic alterations in molecular and physiological processes and is associated with numerous disorders, in part due to increased genetic instability. The aging population is projected to double by 2050, underscoring the urgent need to better understand the relationships between aging and age-related disorders. Repetitive DNA elements are intrinsic sources of genetic instability and have been found to co-localize with mutation hotspots in human cancer genomes. In this study, we explored the relationship between aging and DNA repeat-mediated genetic instability in vivo using an H-DNA-forming mirror-repeat sequence from the cancer-associated human

Pro-differentiation and anti-senescence treatment may be potential strategies for senile osteoporosis therapy. However, the regulatory mechanism underlying osteoblast differentiation and senescence in senile osteoporosis remain to be clarified. In the present study, the preosteoblast cell line MC3T3-E1 was used to induce osteoblast differentiation. The H

Genome instability is a hallmark of aging, with the highly repetitive ribosomal DNA (rDNA) within the nucleolus being particularly prone to genome instability. Nucleolar enlargement accompanies aging in organisms ranging from yeast to mammals, and treatment with many antiaging interventions results in small nucleoli. Here, we report that an engineered system to reduce nucleolar size robustly extends budding yeast replicative lifespan in a manner independent of protein synthesis rate or rDNA silencing. Instead, when nucleoli expand beyond a size threshold, their biophysical properties change, allowing entry of proteins normally excluded from the nucleolus, including the homologous recombinational repair protein Rad52. This triggers rDNA instability due to aberrant recombination, catastrophic genome instability and imminent death. These results establish that nucleolar expansion is sufficient to drive aging. Moreover, nucleolar expansion beyond a specific size threshold is a mortality timer, as the accompanying disruption of the nucleolar condensate boundary results in catastrophic genome instability that ends replicative lifespan.

The age-associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age-related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound anti-aging properties on ISCs. Asn inhibits the hyperproliferation of aging ISCs in Drosophila, maintains intestinal homeostasis, and extends the lifespan of aging flies. Complementarily, Asn promotes the growth and branching of elderly murine intestinal organoids, indicating its anti-aging capacity to enhance ISC function. Mechanistic analyses have revealed that Asn exerts its effects via the activation of the autophagic signaling pathway. In summary, this study has preliminarily explored the potential supportive role of Asn in ameliorating intestinal aging, providing a foundation for further research into therapeutic interventions targeting age-related intestinal dysfunction.

Aging presents a significant challenge to health and social care systems due to the increasing proportion of the elderly population. The identification of reliable biomarkers to assess the progression of aging remains an unresolved question. Circular RNAs (circRNAs) are single-stranded covalently closed RNAs. They have been found to regulate various biological processes. CircRNAs are present in human biological fluids, are relatively stable, and accumulate with age, making them promising as biomarkers of aging. Current information on the expression of circRNAs in aging was analyzed using scientific databases. In this review, we have identified key stages in the study of circRNAs during aging and summarized the current understanding of their biogenesis. By focusing on the role of circRNAs in processes that contribute to aging - such as genomic stability, metabolism, cell death, and signaling pathways - we hypothesize that circRNAs may drive the aging process through their age-related accumulation and resultant deregulation. Examples of age-related differential expression of circRNAs in various species, including humans, are provided. This review highlights the importance of finding novel epigenetic biomarkers of aging, beyond the already identified molecules (circFOXO3, circRNA100783, circPVT1), and highlights circRNAs as a potential therapeutic target for the treatment of age-associated diseases.

A key aspect of brain aging that remains poorly understood is its high regional heterogeneity and heterochronicity. A better understanding of how the structural organization of the brain shapes aging trajectories is needed. Neuroimaging tissue "types" are often collected and analyzed as separate acquisitions, an approach that cannot provide a holistic view of age-related change of the related portions of the neurons (cell bodies and axons). Because neuroimaging can only assess indirect features at the gross macrostructural level, incorporating post-mortem histological information may aid in better understanding of structural aging gradients. Longitudinal design, coupling of gray and white matter (GM, WM) properties, and a biologically informed approach to organizing neural properties are needed. Thus, we tested aging of the regional coupling between GM (cortical thickness, surface area, volume) and WM (fractional anisotropy, mean, axial, and radial diffusivities) structural metrics using linear mixed effects modeling in 102 healthy adults aged 20-94 years old, scanned on two occasions over a four-year period. The association between age-related within-person change in GM morphometry and the diffusion properties of the directly neighboring portion of white matter were assessed, capturing both aspects of neuronal health in one model. Additionally, we parcellated the brain utilizing the histological-staining informed von Economo-Koskinas atlas to consider regional cyto- and myelo-architecture. Results demonstrate several gradients of coupled association in the age-related decline of neighboring white and gray matter. Most notably, gradients of coupling along the heteromodal association to sensory axis were found for several areas (e.g., anterior frontal and lateral temporal cortices, vs pre- and post-central gyrus, occipital, and limbic areas), in line with heterochronicity and retrogenesis theories of aging. Further effort to bridge across data and measurement scales will enhance understanding of the mechanisms of the aging brain.

The biological progression of aging encompasses complex physiological processes. As individuals grow older, their physiological functions gradually decline, including compromised immune responses, leading to immunosenescence. Immunosenescence significantly elevates disease susceptibility and severity in older populations while concurrently compromising vaccine-induced immune responses. This comprehensive review aims to elucidate the implications of immunosenescence for vaccine-induced immunity and facilitate the development of optimized vaccination strategies for geriatric populations, with specific focus on COVID-19, influenza, pneumococcal, herpes zoster, and respiratory syncytial virus (RSV) vaccines. This review further elucidates the relationship between immunosenescence and vaccine-induced immunity. This review presents a systematic evaluation of intervention strategies designed to enhance vaccine responses in older populations, encompassing adjuvant utilization, antigen doses, vaccination frequency modification, inflammatory response modulation, and lifestyle interventions, including physical activity and nutritional modifications. These strategies are explored for their potential to improve current vaccine efficacy and inform the development of next-generation vaccines for geriatric populations.

BackgroundProtein quality control (PQC) is critical for maintaining sarcomere structure and function in cardiac myocytes, and mutations in PQC pathway proteins, such as CRYAB (arginine to glycine at position 120, R120G) and BAG3 (proline to lysine at position 209, P209L) induce protein aggregate pathology with cardiomyopathy in humans. Novel observations in yeast and mammalian cells demonstrate mitochondrial uptake of cytosolic protein aggregates. We hypothesized that mitochondrial uptake of cytosolic protein aggregates and their removal by mitophagy, a lysosomal degradative pathway essential for myocardial homeostasis, facilitates cytosolic protein quality control in cardiac myocytes. MethodsMice with inducible cardiac myocyte specific ablation of TRAF2 (TRAF2icKO), which impairs mitophagy, were assessed for protein aggregates with biochemical fractionation and super-resolution imaging in comparison to floxed controls. Induced pluripotent stem cell (iPSC)-derived cardiac myocytes with R120G knock-in to the CRYAB locus were assessed for localization of the CRYAB protein. Transgenic mice expressing R120G CRYAB protein (R120G-TG) were subjected to both TRAF2 gain-of-function (with AAV9-cardiac Troponin T promoter-driven TRAF2 transduction) and TRAF2 loss-of-function (with tamoxifen-inducible ablation of one Traf2 allele) in cardiac myocytes to determine the effect of mitophagy modulation on cardiac structure, function, and protein aggregate pathology. ResultsCardiomyocyte-specific ablation of TRAF2 results accumulation of mitochondrial and cytosolic protein aggregates and DESMIN mis-localization to protein aggregates. Isolated mitochondria take up cardiomyopathy-associated aggregate-prone cytosolic chaperone proteins, namely arginine to glycine (R120G) CRYAB mutant and proline to lysine (P209L) BAG3 mutant. R120G-CRYAB mutant protein increasingly localizes to mitochondria in human and mouse cardiomyocytes. R120G-TG mice demonstrate upregulation of TRAF2 in the mitochondrial fraction with increased mitophagy as compared with wild type. Adult-onset inducible haplo-insufficiency of TRAF2 resulted in accelerated mortality, impaired left ventricular systolic function and increased protein aggregates in R120G-TG mice as compared with controls. Conversely, AAV9-mediated TRAF2 transduction in R120G-TG mice reduced mortality and attenuated left ventricular systolic dysfunction, with reduced protein aggregates and restoration of normal localization of DESMIN, a cytosolic scaffolding protein chaperoned by CRYAB, as compared with control AAV9-GFP group. ConclusionsTRAF2-mediated mitophagy in cardiac myocytes facilitates removal of cytosolic protein aggregates and can be stimulated to ameliorate proteotoxic cardiomyopathy.

The Information Theory of Aging (ITOA) provides a framework for understanding aging and rejuvenation via changes in epigenetic information. These changes are visualized using Waddington landscape -- a 3D topology that represents cell trajectories during changes in cell identity -- constructed from field decomposition of scRNA velocity data. Studies have demonstrated that the Waddington landscape can serve as a mechanistic model of epigenetic information. It explains how age-driven decline in cellular function and reprogramming-induced rejuvenation can be understood by studying the transformations in the Waddington landscape. This study provides insights into the representation of epigenetic information and discusses how it can be reprogrammed to restore a younger cellular state.

Phthalates are widely used chemicals with ubiquitous human exposure. Evidence indicated that phthalate exposure was associated with an increased risk of aging-related diseases. Klotho is a transmembrane protein with anti-aging functions, and its association with phthalates remains unknown. To find the association between phthalate exposure and serum α-Klotho, a cross-sectional study was performed in 4482 adults (40-79 years old) who completed the National Health and Nutrition Examination Survey (NHANES) (2007-2016). As shown in the results of multivariable linear regression analyses, mono(carboxynonyl) phthalate (MCNP) and mono-n-butyl phthalate (MBP) were inversely associated with α-Klotho, and the regression coefficients of MCNP and MBP were -1.14 (95% confidence interval (CI): -2.00, -0.27) and -0.08 (95% CI: -0.14, -0.02). Subgroup analyses based on the quartiles of each phthalate metabolite showed that both MCNP and MBP were only inversely associated with α-Klotho in the subgroups of the highest levels. For mono-isobutyl phthalate (MIBP), the inverse association with α-Klotho was only statistically significant in the subgroup of the lowest level, and the regression coefficient was -26.87 (95% CI: -52.53, -1.21). Our findings suggest that α-Klotho might be involved in the association of phthalate exposure with aging-related diseases. Future research investigating the causality between phthalates and α-Klotho and its underlying mechanisms is encouraged.

Circular RNAs (circRNAs) have garnered attention for their potential involvement in the regulation of cellular aging processes. Exploring the role and mechanism of circRNAs in cellular senescence may help to identify new anti-aging therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0127071 in renal aging. We employed high-throughput sequencing to assess circRNA expression differences in kidney tissues from young and old groups. qRT-PCR confirmed that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. Cellular senescence was evaluated using SA-β-Gal staining and Masson's trichrome staining. Using RNA Immunoprecipitation (RIP), RNA Pull-Down Assay (RNA pull down), and Western Blot (WB) to study the interaction between hsa_circ_0127071 and aging related pathway proteins. In this study, we found that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. Silencing of EIF4A3, a protein involved in the JAK2/STAT5 signaling pathway, was found to delay the aging process. On the basis of silencing EIF4A3 expression, the JAK2/STAT5 signaling pathway was activated by Erythropoietin (EPO) processing, and the senescence of Human glomerular mesangial cells (HGMCs) increased. After treatment with Losartan (LOS), the activity of JAK2/STAT5 pathway was decreased and the aging process of HGMCs was delayed. Our findings demonstrate that hsa_circ_0127071 promotes renal aging through the EIF4A3/JAK2/STAT5 signaling axis, highlighting a novel potential therapeutic target for the management of renal aging and associated disorders.

The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.

Environmental factors and individual attributes, and their interactions, impact survival, growth and reproduction of an individual throughout its life. In the clonal rotifer Brachionus, low food conditions delay reproduction and extend lifespan. This species also exhibits maternal effect senescence; the offspring of older mothers have lower survival and reproductive output. In this paper, we explored the population consequences of the individual-level interaction of maternal age and low food availability. We built matrix population models for both ad libitum and low food treatments, in which individuals are classified both by their age and maternal age. Low food conditions reduced population growth rate (

Sarcopenia is a significant healthcare challenge in the aging population. Oxidative stress (OS) is acknowledged to play a pivotal role in the pathological progression of sarcopenia. Numerous studies have demonstrated that mitigating or eliminating OS can ameliorate the pathological manifestations associated with sarcopenia. However, current clinical antioxidant therapies often fall short of anticipated outcomes. This bibliometric analysis aims to delineate prevailing research trends, thematic emphases, focal points, and developmental trajectories within the domain of OS in sarcopenia, while also endeavoring to explore prospective anti-oxidative stress strategies for future clinical interventions.

Skin aging is driven by a combination of internal and external mechanisms, with ultraviolet (UV) radiation being a prominent external factor contributing to photoaging. Photoaging manifests through several signs, including decreased skin hydration, diminished elasticity, coarse wrinkles, and dyspigmentation. Cacao beans, known for their flavonoids and polyphenols, offer potential anti-aging benefits. To explore this, we conducted a study using both in vitro experiments and clinical trials. Our results demonstrated that cacao powder significantly improved skin hydration and moisture retention in both experimental settings. Specifically, in UVB-damaged human dermal fibroblasts (HDFs) and H

It is a common observation that individuals within a species age at different rates. Variation in both genetics and environmental interaction are generally thought responsible. Surprisingly, even genetically identical organisms cultured under environmentally homogeneous conditions age at different rates, implying a more fundamental cause of aging. Here we have examined the basis for lifespan variance in haploid, single-celled yeast of Saccharomyces cerevisiae. The probabilistic nature of metabolism means metabolites often, but not always, follow the same route through the metabolic network. We speculate redundancy in metabolic pathway choice is sufficient to explain lifespan variance. To interrogate the reaction flux space of S. cerevisiae we used a model of its intermediary metabolism, comprising 1,150 genes, 4,058 reactions, and 2,742 metabolites (yeast GEM_v8.5.0). We restricted traffic through the metabolic network by knocking out each of the 1,150 genes, then generated a total of 406,500 flux distributions spanning the solution space of the resulting 812 viable mutants. We collected replicative life span (RLS) data for the 812 viable mutants, corresponding to 66,400 individual cells. Four approaches were then employed to test whether reaction flux configuration could be used to predict lifespan: Principal Component Analysis (PCA) in conjunction with non-linear modeling of RLS; deep learning of RLS using either a Regression Neural Network (RNN) or a Classification Neural Network (CfNN); and deep learning using a convolutional neural network (CNN) following conversion of flux distributions to pixelated images. The four approaches reveal a core network of highly correlated reactions controlling aging rate that is sufficient to explain all lifespan variance. It includes biosynthetic pathways encompassing ceramides, monolysocardiolipins, phosphoinositides, porphyrin and glycerolipids. Our data lead to two novel conclusions. First, variance in the replicative lifespan of S. cerevisiae is an emergent property of its metabolic network. Second, there is convergence among metabolic configurations toward three meta-stable flux states - one associated with extended life, another with shortened life, and a third with wild type life span. One Sentence SummaryTraffic routes and rates through the metabolic network of S. cerevisiae fully account for variance in replicative lifespan.

The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline.

To identify the metabolic underpinnings of retinal aging and examine how it is related to mortality and morbidity of common diseases.

Senescent osteocytes are key contributors to age-related bone loss and fragility; however, the impact of mechanobiological changes in these cells remains poorly understood. This study provides a novel analysis of these changes in primary osteocytes following irradiation-induced senescence. By integrating subcellular mechanical measurements with gene expression analyses, we identified significant, time-dependent alterations in the mechanical properties of senescent bone cells. Increases in classical markers such as SA-β-Gal activity and p16

We aimed to explore the age-dependent epigenetic variability on the X-chromosome with consideration of X-chromosome inactivation by applying a sex-stratified regression analysis to DNA methylation array data on X-linked CpGs in aging identical twins. We found 13 X-linked CpGs showing age-related significant increase in variability in males (FDR < 0.05) but none in females. In females, we found a significantly higher proportion of CpGs showing increased variability with age among nominally significant (

Functional capacity is an important objective health metric, and relies on the maintenance of physiological homeostasis. Autonomic nervous system is known to coordinates the maintenance of multi-organ homeostasis. The objective of this study was to examine the association of autonomic nervous system function with functional capacity in adults aged 55 years and older. A cohort of 542 adults (mean age of 70.1 years) received repeated measurements of heart rate variability, an autonomic nervous system function marker, and chair rise time, a functional capacity measure. Linear mixed models analysis showed that 1 SD lower powers in low-frequency range at baseline was associated with a 0.11 (95% CI 0.01-0.21) s/year faster increase in chair rise time during the follow-up, whereas 1 SD increase in powers in high-frequency range and 1 SD decrease in the ratio of powers in low-frequency range to powers in high-frequency range during the follow-up were associated with a 0.22 (95% CI 0.06-0.39) s and 0.17 (95% CI 0.01-0.33) s increase in chair rise time. In conclusion, autonomic nervous system function and its changes were longitudinally associated with changes in functional capacity in older adults.

Divergent thinking (DT), the ability to generate alternative responses to open-ended problems, has become an increasingly relevant topic in aging research due to its inverse relationship with cognitive decline.

This study identifies senescent osteocytes in the femur and tibia of young rodents and explores their role in bone remodeling. The proximity of osteoclasts to senescent osteocytes was observed, which is a new finding. Cultured osteocytes, sorted using a podoplanin antibody in FACS, exhibited osteocytic characteristics and increased senescence-related genes. Senescent osteocytes secreted cytokines associated with senescence, remodeling, and inflammation. Notably, IGF1 and MMP2 were elevated in podoplanin-positive (pdpn

Frailty is highly prevalent in old age and is associated with a high risk of mortality. Few studies have evaluated frailty as a predictor of mortality in the oldest old. This systematic review and meta-analysis aims to determine the mortality risk associated with frailty in this age group.

Chronic inflammation has been associated with the progression of age-related macular degeneration (AMD) and diabetic retinopathy (DR), and the levels of various inflammatory factors are significantly increased in intraocular fluids of patients with AMD and DR. Therefore, elucidating the roles of inflammatory factors in the oxidative damage of RPE cells will help uncover the pathogenesis of AMD and DR. We have previously demonstrated that E2F1 plays an important role in the antioxidant capacity of RPE cells. Here, our transcriptome analysis shows that E2F1 affected the expressions of DNA repair genes in RPE cells. In addition, we found that E2F1 transactivated the splicing factor SRSF1. SRSF1 knockdown promoted DNA oxidative damage and apoptosis and decreased the mRNA stability of DNA repair genes XRCC2, POLK and LIG4 in RPE cells. Moreover, we found that SRSF1 could bind to the RNA stabilizing factor MATR3, and knockdown of the latter affected the mRNA stability of these DNA repair genes. Notably, interleukin-6 (IL-6), an inflammatory factor upregulated in intraocular fluids of patients with AMD and DR, decreased SRSF1 expression by inducing acetylation of E2F1 at the K125 position. Consistently, SRSF1 overexpression relieved IL-6-induced DNA oxidative damage and apoptosis in RPE cells. In vivo experiment results also confirmed that IL-6 could aggravate retinal oxidative damage. In conclusion, high levels of IL-6 in the eyes of patients with AMD and DR destabilize the mRNAs of DNA repair genes by disrupting the expression of SRSF1, leading to abnormal repair of DNA oxidative damage in RPE cells.

This article examines the framing and public perception of longevity biotechnology, or geroscience, which aims to extend both healthspan and lifespan by targeting the biological processes of aging. Although often seen as moving into the mainstream, questions remain about its ability to meet these ambitious goals, given the complexities of understanding and manipulating aging biology. Drawing on an analysis of qualitative studies and surveys conducted over the past two decades, this paper explores how public attitudes toward anti-aging science are framed, suggesting that studies often emphasize life extension over healthspan gains. Findings reveal mixed reactions, with both interest in and ambivalence about the desirability of extended lifespans. In response, this paper recommends that stakeholders in longevity biotechnology engage with the public by understanding unmet health needs rather than assuming a widespread embrace of lifespan extension. The article underscores the importance of aligning public engagement strategies with realistic scientific expectations to foster credibility and trust; promises should be grounded in current scientific evidence and tempered by feasibility. Addressing societal concerns and fostering dialogue on the ethical and social implications of manipulating aging processes could lay a foundation for responsible progress in geroscience and biogerontology, supporting a more informed, inclusive conversation between science and society as these fields advance.

Caloric intake can greatly affect many aspects of an organism's life. A deficiency of calories can lead to stress resulting in decreased fecundity, insufficient calories to maintain tissues and increased lifespan. Conversely, increasing caloric density increases fecundity and decreases lifespan. Despite decades of work exploring food quality and quantity on physiology in the model species

Population aging affects society, with a profound impact on daily activities for those of a low socioeconomic status and with motor impairments. Social assistive robots (SARs) and monitoring technologies can improve older adults' well-being by assisting with and monitoring home activities.