Longevity Papers

The aim of this study was to explore the potential of adhering to the American Heart Association's updated Life's Essential 8 (LE8) scores in delaying biological aging amid growing concerns about aging populations and related diseases.

GDF15 (growth differentiation factor 15) is a marker of cellular and mitochondrial energetic stress linked to physical-mental illness, aging, and mortality. Here, we describe the psychobiological regulation of plasma and saliva GDF15 in four human studies including 3,599 samples from 148 healthy individuals. We report two main observations establishing GDF15 as a novel tractable biomarker of psychosocial stress. 1) In two experimental laboratory studies, socio-evaluative stress rapidly elevates GDF15 and lactate, two molecular markers of energetic/reductive stress. 2) Similar to other stress-related metabolic hormones, we also find that saliva GDF15 exhibit a robust awakening response, being highest at the time of waking up and declining by [~]42-92% within 30-45 minutes. These data position GDF15 as a dynamic biomarker of psychosocial stress accessible in human blood and saliva, pointing towards a shared psychobiological pathway linking mental and mitochondrial energetic stress. These foundational observations open the door to large-scale studies using GDF15 to non-invasively probe how acute psychosocial factors promote cellular and mitochondrial and energetic stress contributing to the stress-disease cascade across the lifespan. Significance statementThis study uncovers the dynamic psychobiological regulation of plasma and saliva GDF15, establishing it as a biomarker of acute psychosocial stress. Using over 3,500 samples we demonstrate that acute socio-evaluative stress increases within minutes both GDF15 and lactate, reflecting reductive stress. High-intensity sampling over multiple weeks also confirms novel dynamics around the saliva GDF15 awakening response. These findings highlight a connection between acute psychosocial stress and mitochondrial energetic stress, offering new opportunities to investigate how stress becomes biologically embedded and contributes to health trajectories across the human lifespan.

Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. In this Review, we discuss the composition, dynamics and heterogeneity of the SASP as well as the mechanisms underlying its induction and regulation. We describe the various biological properties of the SASP, its beneficial and detrimental effects in different physiological and pathological settings, and its impact on overall health span. Finally, we discuss the use of the SASP as a biomarker and of SASP inhibitors as senomorphic interventions to treat cancer and other age-related conditions.

Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in epigenetic markers that are retained for many years.We investigated the effect of maternal major financial problems (MFP) and material deprivation (MD) on their children's epigenome in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Epigenetic aging, measured with epigenetic clocks, was weakly accelerated with increased MFP. In subsequent EWAS, MFP, and MD showed strong, independent programing effects on children's genomes. MFP in the period from birth to age seven was associated with genome-wide epigenetic modifications on children's genome visible at age 7 and partially remaining at age 15.These results support the hypothesis that physiological processes at least partially explain associations between early-life adversity and health problems later in life. Both maternal stressors (MFP/MD) had similar effects on biological pathways, providing preliminary evidence for the mechanisms underlying the effects of low socioeconomic status in early life and disease outcomes later in life. Understanding these associations is essential to explain disease susceptibility, overall life trajectories and the transition from health to disease.

The senescence of endothelial cells is of great importance involving in atherosclerosis (AS) development. Recent studies have proved the protective role of mesenchymal stem cell-derived extracellular vesicles in AS, herein, we further desired to unvei their potential regulatory mechanisms in endothelial cell senescence.