Aging & Longevity

Aging represents the main risk factor for the development of several diseases, including cardiovascular and metabolic conditions, neurodegenerative disorders and cancer. As the number of elderly people is increasing worldwide, different strategies to counteract age-related diseases have been investigated. Recently, the use of molecular hydrogen (H(2)) as a preventive and therapeutic approach has been proposed due to its antioxidant and anti-inflammatory properties, its ability to regulate cell...

HealthAge was devised by a conglomerate of research groups in Toulouse, France, with the combined goal of narrowing the lifespan-healthspan gap through novel translational bench-to-bedside research studies. HealthAge comprises the "INStitute for Prevention" "healthy aging" and "medicine Rejuvenative" (INSPIRE) human translational, outbred SWISS mice and African turquoise killifish (GRZ strain) cohorts in which aging is studied based on the concept of intrinsic capacity (IC). In this narrative...

Aging is characterized by a deterioration of stem cell function, but the feasibility of replenishing these cells to counteract aging remains poorly defined. Our study addresses this gap by developing senescence (seno)-resistant human mesenchymal progenitor cells (SRCs), genetically fortified to enhance cellular resilience. In a 44-week trial, we intravenously delivered SRCs to aged macaques, noting a systemic reduction in aging indicators, such as cellular senescence, chronic inflammation, and...

CONCLUSIONS: This research reveals the social participation dynamics in rural older adults and their effects on medical care utilization in China. Social participation can significantly promote outpatient care utilization among rural older adults. Targeted policy and practice are needed for those with low levels of social participation in rural areas.

Synaptic pruning (SP) is a critical process in brain development and maintenance, essential for refining neural circuits by eliminating weak or redundant synapses. Dysregulation of SP has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Studying the regulation of SP genes across the lifespan and their variation by sex and age is crucial to understanding the interplay between aging, sex, and AD pathogenesis. This study comprehensively analyzes the expression of...

Repair of muscle damage declines with age due to the accumulation of dysfunctional muscle stem cells (MuSCs). Here, we uncover that aged MuSCs have blunted prostaglandin E2 (PGE2)-EP4 receptor signaling, which causes precocious commitment and mitotic catastrophe. Treatment with PGE2 alters chromatin accessibility and overcomes the dysfunctional aged MuSC fate trajectory, increasing viability and triggering cell cycle re-entry. We employ neural network models to learn the complex logic of...

Sirtuin enzymes are deeply associated with senescence and aging. Sirtuin proteins are tightly regulated, but how their levels are governed during aging and how they elicit tissue-specific cellular changes are unclear. Here, we demonstrate that SIRT7 undergoes proteasomal degradation during senescence via targeting by the E3 ligase TRIP12. We identified the transcription factor nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) as an interactor of SIRT7 and found NUCKS1...

Cellular senescence is a state of stable cell-cycle arrest induced by various intrinsic and extrinsic stressors, serving as a protective mechanism to prevent the proliferation of damaged cells. While this process is crucial for tissue homeostasis and tumor suppression, the progressive accumulation of senescent cells (SnCs) over time is implicated in age-related pathologies, including immune dysfunction and cancer. In oncology, senescence plays a paradoxical role: it can inhibit tumor development...

Senescence is the gradual process of aging in tissues and cells, and a primary cause of aging-associated diseases. Among them, intestinal stem cells (ISCs) experience exhaustion during aging, leading to reduced regenerative capacity in the intestinal crypt, which impairs intestinal function and contributes to systemic health issues. Given the critical role ISCs play in maintaining intestinal homeostasis, preventing their senescence is essential for preserving intestinal function. Among the...

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The discovery of transgenerational epigenetic inheritance and the unraveling of its molecular mechanisms are currently solving previously puzzling challenges that Mendelian genetics based solely on DNA could not explain, leading to significant paradigm shifts across various fields of biology. There has been a long-standing controversy over the factors determining the caste fate of individuals in social insects. Increasing evidence supports heritable influences on division of labor. Here, we...

Alterations in energy metabolism may drive fatigue in older age, but prior research primarily focused on skeletal muscle energetics without assessing other systems and utilized self-reported measures of fatigue. We tested the association between energy metabolism in the brain and an objective measure of fatigability in the Study of Muscle, Mobility and Aging (N = 119, age 76.8 ± 4.0 years, 59.7% women). Total brain cerebral metabolic rate of oxygen (CMRO(2)) was measured using arterial spin...

Effective memory formation declines in human aging. Diminished neural selectivity-reduced differential responses to preferred versus nonpreferred stimuli-may contribute to memory decline, but its drivers remain unclear. We investigated the effects of top-down attention and preclinical Alzheimer's disease (AD) pathology on neural selectivity in 166 cognitively unimpaired older participants using functional magnetic resonance imaging during a word-face/word-place associative memory task. During...

Microglia, the resident immune cells of the brain, are now recognized as being active participants in the onset and progression of many neurological and neuropsychiatric disorders. As a result, substantial effort has been made in finding ways to target, deplete or modulate the aberrant phenotypes of the microglia that are present in these different disease states, albeit with varied levels of success. The gut microbiota has recently emerged as a master regulator of microglia throughout the...

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Presbycusis, one of the most widespread disorders, is in part associated with the loss of temporal precision within the central auditory system. A contributor to the dysfunctional temporal precision during aging is the substantial downregulation of GABA in the central inferior colliculus (ICc), the hub of ascending and descending inputs of the auditory midbrain. However, how GABAergic inputs across the tonotopic axis of the ICc change with age has not been well explored. We sought to determine...

Ageing is the most important risk factor for many common human diseases, including cancer, diabetes, neurodegeneration and cardiovascular disease. Consequently, combating ageing itself has emerged as a rational strategy for addressing age-related multimorbidity. Over the past three decades, multiple genetic and pharmacologic interventions have led to substantial extension of lifespan and healthspan in model organisms. However, it is unclear whether these interventions target the causal...

The blood-brain barrier (BBB) restricts the passage of protein-rich fluids through tight junctions (TJs) formed between brain endothelial cells (BECs). BBB restrictiveness diminishes with aging, but the underlying mechanisms remain unclear. BECs establish physical contact with pericytes via N-cadherin homophilic adhesion. In cortex tissue from young and middle-aged patients, the age-related loss of vascular N-cadherin corresponds with the disruption of occludin TJs. Genetic deletion of...

Cancer therapy is limited by resistance to standard-of-care chemotherapeutic and/or by treatment-associated toxicity. Identifying molecular mechanisms that modulate cellular toxicity is crucial for enhancing treatment efficacy. We characterize CDADC1, a vertebrate-specific orphan enzyme, as an unprecedented eukaryotic dCTP deaminase. CDADC1 catalyzes the conversion of dCTP into dUTP. While bacteria use this activity to sustain proliferation, CDADC1 evolved independently and is not required for...

Skeletal muscle is a primary tissue of dysfunction during both aging and obesity. Recently, the coincidence of obesity and aging has gained attention due to the intersection of the obesity epidemic with an aging demographic. Both aging and obesity are associated with marked defects in skeletal muscle metabolic health. Despite these findings, we have a poor understanding of how obesity and aging may interact to impact skeletal muscle mass and metabolic health. Therefore, we investigated the...