Aging & Longevity

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 medications has accelerated the development of therapies aimed at slowing aging. In this study, using IMR90 cells and aged mice, 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...

The relationship between the brain and aging remains unclear. Our objective is to explore the causal connections between brain structure,gene expression, and traits associated with aging. Mendelian randomization(MR) analysis was conducted to explore the associations between brain structures and aging-related traits including GrimAge acceleration(GrimAA), PhenoAge acceleration (PhenoAA), HannumAge acceleration(HannumAA), HorvathAge acceleration(HorvathAA), and leukocyte telomere length(LTL). The...

The aim of this study was to establish reference values for the Five-Times-Sit-to-Stand Test (FTSST) in a large, population-representative sample from 14 European countries. Data were collected among 45,470 participants aged 50 + years, as part of the 5th wave of the Survey of Health, Ageing and Retirement in Europe. The reference values for the FTSST were calculated as the 5th, 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th, 90th, and the 95th weighted percentile. The analyses were stratified...

Hematopoietic aging is characterized by chronic inflammation associated with myeloid bias, hematopoietic stem cell (HSC) accumulation, and functional HSC impairment. Yet it remains unclear how inflammation promotes aging phenotypes. Nuclear factor κB (NF-κB) both responds to and directs inflammation, and we present an experimental model of elevated NF-κB activity ("inhibitor of κB deficient" [IκB^(-)]) to dissect its role in hematopoietic aging phenotypes. We find that while elevated NF-κB...

Mast cells (MC) are long-lived important immune effectors that control inflammation, allergies, and innate immunity reactions, but the expression of specific markers in replicative and stress-induced senescence in this cell type, together with its relevance in vivo, has not been described. Here, bone marrow-derived MCs (BMMC) were generated from young C57BL6/J mice and kept in culture for a long time or treated with the well-known stressor bacterial lipopolysaccharide (LPS) to promote...

Sirtuin 3 (SIRT3), a NAD⁺-dependent deacetylase localized in the mitochondrial matrix, has emerged as a central regulator of aging and age-related pathologies. This review synthesizes evidence demonstrating SIRT3's tripartite anti-senescence mechanisms: 1) Enhancement of mitophagy via p53 deacetylation-mediated mitochondrial quality control, 2) Reinforcement of antioxidant defenses through SOD2/IDH2 activation, and 3) Optimization of metabolic homeostasis by coordinating fatty acid β-oxidation...

Cognitive enhancement and neuroplasticity are interconnected terms. Neuroplasticity is an intrinsic brain capability that enables it to adapt and learn throughout life. It involves significant reorganization of neural circuits which is evident not only during normal human development but also occurs following early injury. As aging exerts a detrimental effect on various bodily systems, the extent of neuroplasticity also declines considerably. Recent evidences emphasize that cognitive enhancement...

The endoplasmic reticulum (ER) is the largest organelle in eukaryotic cells, and it plays a crucial role in regulating various biological processes, including protein folding, translation, and structural maturation. Accurate protein modification is essential for maintaining oxidative stress, apoptosis, and cellular senescence in the organism. The regulation of protein homeostasis involves three biological processes: endoplasmic reticulum stress (ERS), endoplasmic reticulum autophagy (ERPA), and...

Biomolecular condensates play wide-ranging roles in cellular compartmentalization and biological processes. However, their transition from a functional liquid-like phase into a solid-like state-usually termed as condensate ageing-represents a hallmark associated with the onset of multiple neurodegenerative diseases. In this study, we design a computational pipeline to explore potential candidates, in the form of small peptides, to regulate ageing kinetics in biomolecular condensates. By...

Meiotic maturation of vertebrate oocytes occurs in the near-absence of transcription. Thus, female fertility relies on timely translational activation of maternal transcripts stockpiled in full-grown prophase-I-arrested oocytes. However, how expression of these mRNAs is suppressed to maintain the long-lasting prophase-I arrest remains mysterious. Utilizing fast-acting TRIM-Away, we demonstrate that acute loss of the translation repressor 4E-T triggers spontaneous release from prophase-I arrest...

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The mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays an important role in this phenomenon. First, by studying 454,098 UK Biobank participants, we find that, unlike most CH subtypes, splicing-factor-mutant CH is more common in those with shorter genetically predicted telomeres, as is CH with mutations in PPM1D...

The comparative biology of aging leverages the remarkable diversity in aging rates and lifespans across species to uncover naturally evolved adaptations that promote longevity, disease resistance and injury resilience. The beauty of comparative biology is that it discovers adaptations that evolved outside of the protected laboratory environment, shaped by natural selection under real-world pressures. In this Review, we outline key approaches in comparative biology of aging studies, including the...

Maternal malnutrition affects millions of people worldwide in two main ways: through food insecurity and hunger, as well as through diets high in ultra-processed, low-nutrient foods. These effects are often linked to deficiencies in specific macronutrients and micronutrients, which can lead to organ-specific consequences in the biological development of the child-a context explored within the framework of the Developmental Origins of Health and Disease (DOHaD). Given the extensive effects of...

CONCLUSION: This study identifies specific sEMG-derived features, particularly signal shape and complexity metrics, as potential non-invasive biomarkers for neuromuscular decline in sarcopenia. The Post-stab epoch emerges as a sensitive window for detecting deficits in motor control, supporting the use of perturbation-based tasks and sEMG analysis for early detection, monitoring, and intervention planning in aging populations.

CONCLUSIONS: This systematic review and meta-analysis suggests that homeless individuals have a dementia prevalence higher than population-based studies of housed adults of a similar age, where the estimated prevalence is under 3%. Research on models of care aimed at reducing homelessness in those experiencing dementia is needed.

As the population of individuals living with Alzheimer's disease and related dementias (AD/ADRD) continues to grow, so does the need for a well-prepared and stable dementia care workforce. The National Dementia Workforce Study (NDWS) represents a significant investment to understand the demographics, experiences, and magnitude and scope of challenges faced by the professional and direct care workforce providing care to people with dementia. This article discusses the NDWS's goals, data...

CONCLUSIONS: In this French cohort, SCORE2-OP overestimated cardiovascular risk and showed moderate discrimination. EDS improved SCORE2-OP performance in intermediate cardiovascular risk groups where treatments are uncertain, highlighting its clinical relevance; although implications for prevention strategies require further study.

Centenarians exhibit remarkable disease resilience despite chronic low-grade inflammation. We investigated the inflammation-related proteome response to acute exercise in seven centenarians (100-104 years). Exercise downregulated 52 proteins (e.g., TNF, IL10, IL1RN, CCL family members) involved in immune cell trafficking, apoptosis, and cytokine regulation. Even at the extreme end of the lifespan, humans retain molecular responsiveness to exercise, with modulation of inflammation-related...

Telomeres protect the chromosome ends from deleterious DNA damage response and repair activities. In humans, telomerase maintains telomere length in germ and stem cells, but not in most somatic cells. Consequently, telomeres shorten with cell division and age, limiting cell proliferation and protecting against cancer. When telomeres become critically short, they may also cause senescence, inflammation, and organ failure, which are major drivers of aging. Therefore, maintaining an optimal,...