Aging & Longevity
Asymmetric division in a two-cell-like state rejuvenates embryonic stem cells
A fundamental question in biology is whether all cells age. Embryonic stem cells (ESCs) defy the norm as rare normal cells capable of indefinite in vitro passage. However, the mechanisms underlying ESC lineage immortality remain unresolved. Using long-term live-cell imaging to follow the fates of single ESCs, we show that ESC lineage renewal is achieved through sporadic entry into a state characterized by the expression of two-cell embryo-specific markers. During this state, cells undergo...
Mitochondrial superoxide regulates nuclear envelope integrity and ageing via redox-mediated lipid metabolism
The nuclear envelope (NE) is essential for cellular homeostasis, yet its integrity declines with age, accelerating functional deterioration. Here we report a mitochondria-to-NE signalling pathway that safeguards NE integrity through redox-dependent lipid metabolism. In Caenorhabditis elegans, reducing mitochondrial ETC activity preserves NE morphology during ageing. This effect requires developmental mitochondrial superoxide, which downregulates SBP-1 (SREBP orthologue) and suppresses...
Mitochondrial superoxide signals shield the nucleus to delay ageing
No abstract
Aging clocks delineate neuron types vulnerable or resilient to neurodegeneration and identify neuroprotective interventions
Different neuron types show distinct susceptibility to age-dependent degeneration, yet the underlying mechanisms are poorly understood. Here we applied aging clocks to single neuron types in Caenorhabditis elegans and found that distinct neurons differ in their biological age. Ciliated sensory neurons with high neuropeptide and protein biosynthesis gene expression show accelerated aging and degeneration, correlating with loss of function, which could be prevented by pharmacological inhibition of...
Treatment resistance to platinum-based chemotherapy in lung and ovarian cancer is driven by a targetable TGFbeta senescent secretome
Platinum-based chemotherapy is commonly used for non-small cell lung cancer (NSCLC) and high-grade serous ovarian cancer (HGSOC) treatments, yet clinical outcomes remain poor. Cellular senescence and its associated secretory phenotype (SASP) can have multiple tumor-promoting activities, but both are largely unexplored in these cancers. In this study, using xenograft, orthotopic and Kras^(G12V)-driven murine NSCLC models, we demonstrate that cisplatin-induced senescence strongly promotes...
Household mold exposure and arthritis in older Chinese adults: evidence from the Chinese Longitudinal Healthy Longevity Survey (CLHLS)
CONCLUSIONS: Our findings indicate that both mold exposure and analgesic use are associated with an increased likelihood of arthritis in older adults, underscoring the need to improve damp and deteriorating housing conditions and to promote the rational use of analgesics to support healthy aging.
Sex-specific nonlinear DNA methylation aging trajectories reveal biomarkers of cancer risk and inflammation
CONCLUSIONS: Our results uncover sex-specific, nonlinear aging programs that capture the dynamics of epigenetic change beyond linear models. These findings provide potential candidate biomarkers for early disease risk and advance understanding of how aging trajectories diverge between sexes.
Novel multi-omic biomarkers to combat oocyte and ovarian aging
Understanding oocyte and ovarian aging has become critically important, as trends in family planning evolve, with many women choosing to have children later in life. The ovary, a crucial organ in female reproduction, is particularly susceptible to age-related changes and is one of the organs that exhibit functional deterioration most distinctly with age. The aging of female reproductive systems also affects longevity and various health outcomes. A better understanding of both oocyte and ovarian...
Polluting cooking fuels and life satisfaction among middle-aged and older adults: a cross-sectional study from the Longitudinal Ageing Study in India
Polluting cooking fuels are a major source of household air pollution and may reduce life satisfaction (LS). Yet, this relationship remains unexplored in India where polluting fuel use is still widespread. We utilized cross-sectional data from the Longitudinal Aging Study in India, a nationally representative study of individuals aged 45 years and above. Cooking fuel type was classified as households using clean fuels (CF) or non-CF. Based on kitchen type, non-CF was categorized into non-CF in...
Age-related vs. disease-related: how perceptions of geriatric syndromes shape health-seeking behavior in older adults
CONCLUSION: This explorative study suggests that the individual perceptions of GS may impact the use of medical services. Future confirmatory studies are necessary to develop targeted interventions addressing these perceptions in order to improve the health behavior of older adults.
Randomized, double-blind, placebo-controlled trial of fecal microbiota transplantation from young physically active donors to promote resilient aging: clinical trial protocol (ARMOR study)
No abstract
Leukocyte telomere length and circulating MiRNAs in relation to cardiovascular outcomes in older adults
No abstract
Associations of chinese-modified MIND diet with low muscle mass and physical performance among old adults in china: findings from the CLHLS 2018 national survey
CONCLUSION: Greater adherence to the cMIND dietary pattern is independently associated with lower probability of LMM and better physical performance among older Chinese adults. These findings suggest potential benefits of promoting MIND diet principles for maintaining musculoskeletal health in aging populations.
Gut Microbiota-Derived Metabolites as Immune Modulators in Aging and Age-Related Chronic Inflammatory Diseases
Age-associated dysbiosis, marked by shifts in the composition of gut microbiota and gut microbiota-derived metabolites (GMDMs), is increasingly implicated in driving systemic low-grade inflammation during aging. The disrupted GMDM pools, including altered levels of short-chain fatty acids (SCFAs), secondary bile acids (BAs) and tryptophan (Trp) metabolites, lead to mucosal barrier dysfunction, immunometabolic dysregulation, and modulation of innate and adaptive immune cells. In turn, this...
Aging and neuropathic pain: Mitochondria-to-glia cascade, system mechanisms, and therapeutic strategies
Neuropathic pain (NP) creates a severe pathological condition that primarily affects elderly people because of their accumulated neurobiological changes that make them more susceptible to persistent pain. The aging process leads to multiple mechanisms that combine neurodegeneration with immunosenescence and mitochondrial dysfunction with impaired autophagy and glial priming, and ion channel dysregulation to create a nociceptive environment. This review examines how mitochondrial breakdown and...
Blood Flow and Angiogenesis; Major Mechanisms Mediating Healthful Longevity
While human lifespan has increased dramatically over the past century, the extension of healthspan, the period free of chronic age-related disease, has lagged behind. Blood flow and angiogenesis are significantly reduced in aging humans, playing a crucial role in mediating cardiovascular disease and heart failure - major causes of reduced lifespan. However, these mechanisms have not been studied as extensively as cellular and molecular mechanisms in animal models. Healthful aging, due to...
Uncovering treatment effect heterogeneity in pragmatic gerontology trials
Detecting heterogeneity in treatment response enriches the interpretation of gerontologic trials. In aging research, estimating the intervention's effect on clinically meaningful outcomes poses analytical challenges when outcomes are truncated by death. For example, in the Whole Systems Demonstrator trial, a large cluster-randomized study evaluating telecare among older adults, the overall effect of the intervention on quality of life was found to be null. However, this marginal intervention...
External Validation of SCORE2-OP for Predicting Cardiovascular Mortality in Frail Geriatric Outpatients
CONCLUSIONS AND IMPLICATIONS: In a frail older outpatient population, SCORE2-OP showed notable discrimination for CVD mortality in those without ASCVD history. This suggests that SCORE2-OP can be used for CVD risk estimation in these frail outpatients.
p16-mediated G0/G1 cell cycle arrest leads to SASP and fibrosis in Fuchs endothelial corneal dystrophy
Fuchs endothelial corneal dystrophy (FECD) is an age-related disorder characterized by excessive extracellular matrix (ECM) deposition and loss of corneal endothelial cells (CEnCs), eventually leading to corneal blindness. Despite known environmental and genetic contributors, the roles of aging and hormonal influences, particularly in the predominantly female population, remain underexplored in FECD. This study investigates the impact of chronic exposure to combined ultra-violet (UV-A) light and...
Delivery of peptide coacervates to form stable interaction hubs in cells
Cells contain membrane-bound and membraneless organelles that operate as spatially distinct biochemical niches. However, these reaction centers lose fidelity due to aging or diseases. A grand challenge for biomedicine is restoring or augmenting cellular functionalities. An excited strategy is the delivery of protein-based materials that can directly interact with cellular biological networks. In this study, we sought to develop long-lasting materials capable of cellular uptake, akin to...
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