Longevity Papers

Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets.

Yushuang Deng, Ting Liu, Enzo Scifo ... · Cellular Senescence · Translational Biogerontology Lab, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. · pubmed

The accumulation of senescent cells is thought to play a crucial role in aging-associated physiological decline and the pathogenesis of various age-related pathologies. Targeting senescence-associated cell surface molecules through immunotherapy emerges as a promising avenue for the selective removal of these cells. Despite its potential, a thorough characterization of senescence-specific surface proteins remains to be achieved. Our study addresses this gap by conducting an extensive analysis of the cell surface proteome, or "surfaceome", in senescent cells, spanning various senescence induction regimes and encompassing both murine and human cell types. Utilizing quantitative mass spectrometry, we investigated enriched cell surface proteins across eight distinct models of senescence. Our results uncover significant changes in surfaceome expression profiles during senescence, highlighting extensive modifications in cell mechanics and extracellular matrix remodeling. Our research also reveals substantive heterogeneity of senescence, predominantly influenced by cell type and senescence inducer. A key discovery of our study is the identification of four unique cell surface proteins with extracellular epitopes. These proteins are expressed in senescent cells, absent or present at low levels in their proliferating counterparts, and notably upregulated in tissues from aged mice and an Alzheimer's disease mouse model. These proteins stand out as promising candidates for senotherapeutic targeting, offering potential pathways for the detection and strategic targeting of senescent cell populations in aging and age-related diseases.

Longevity Relevance Analysis (5)

The paper addresses the characterization of senescence-associated cell surface proteins, which is directly related to the mechanisms of cellular senescence and its role in aging and age-related diseases. By identifying potential senotherapeutic targets, the research contributes to understanding how to selectively remove senescent cells, which is a significant aspect of addressing the root causes of aging. The findings are important as they advance the field of senotherapy, but they do not represent a major breakthrough that could transform the field, hence the score of 5.

The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging.

Jitendra Kumar Sinha, Khanak Jorwal, Krishna Kumar Singh ... · Aging · GloNeuro, Sector 107, Vishwakarma Road, Noida, Uttar Pradesh, 201301, India. jitendrakumarsinha@gmail.com. · pubmed

Mitochondria are central to cellular energy production, and their dysfunction is a major contributor to oxidative stress and chronic inflammation, pivotal factors in aging, and related diseases. With aging, mitochondrial efficiency declines, leading to an increase in ROS and persistent inflammatory responses. Therapeutic interventions targeting mitochondrial health show promise in mitigating these detrimental effects. Antioxidants such as MitoQ and MitoVitE, and supplements like coenzyme Q10 and NAD + precursors, have demonstrated potential in reducing oxidative stress. Additionally, gene therapy aimed at enhancing mitochondrial function, alongside lifestyle modifications such as regular exercise and caloric restriction can ameliorate age-related mitochondrial decline. Exercise not only boosts mitochondrial biogenesis but also improves mitophagy. Enhancing mitophagy is a key strategy to prevent the accumulation of dysfunctional mitochondria, which is crucial for cellular homeostasis and longevity. Pharmacological agents like sulforaphane, SS-31, and resveratrol indirectly promote mitochondrial biogenesis and improve cellular resistance to oxidative damage. The exploration of mitochondrial therapeutics, including emerging techniques like mitochondrial transplantation, offers significant avenues for extending health span and combating age-related diseases. However, translating these findings into clinical practice requires overcoming challenges in precisely targeting dysfunctional mitochondria and optimizing delivery mechanisms for therapeutic agents. Continued research is essential to refine these approaches and fully understand the interplay between mitochondrial dynamics and aging.

Longevity Relevance Analysis (5)

Mitochondrial therapeutics can mitigate oxidative stress and inflammation associated with aging. The paper addresses the root causes of aging by focusing on mitochondrial dysfunction and its role in age-related diseases, making it relevant to longevity research.