Aging & Longevity
delta133p53alpha-mediated inhibition of astrocyte senescence and neurotoxicity as a possible therapeutic approach for neurodegenerative diseases
Non-neuronal glial cells in the brain, such as astrocytes, play essential roles in maintaining the functional integrity of neuronal cells. A growing body of evidence suggests that cellular senescence of astrocytes, characterized by loss of proliferative potential and secretion of neurotoxic cytokines, makes significant contribution to neurotoxicity in Alzheimer's disease and a wide range of other neurodegenerative diseases. This review discusses the beneficial effects of Δ133p53α, a natural p53...
Age-related dysregulation of proteasome-independent K63 polyubiquitination in the hippocampus and amygdala
Cognitive decline with aging is a complex process involving multiple brain regions and molecular mechanisms. While the role of the canonical protein degradation function of the ubiquitin-proteasome system (UPS) has been well studied in the context of aging and age-associated memory loss, the non-proteolytic functions of ubiquitin activity remain poorly understood. Here, we investigated the role of lysine-63 (K63) polyubiquitination, the most abundant form of proteasome-independent...
Short Physical Performance Battery or Chair Stand: Which Better Predicts Disability Among High-Functioning Older Adults?
CONCLUSIONS AND IMPLICATIONS: SPPB ≤11 points and CST ≥11.5 seconds more accurately identified the risk of incident IADL/BADL disability than previously recommended cutoff points. As both instruments were similar in predicting trajectories of incident disability, the CST may represent a more practical choice for clinical screening, given its simplicity and shorter administration time.
Global and tract-specific differences between younger and older adults in DTI measures of white matter integrity
Prior research utilizing diffusion tensor imaging (DTI) to examine cerebral white matter microstructural integrity among adults has established that increasing age is associated with poorer white matter health. While age effects on DTI measures of white matter integrity have been shown to vary in strength across different white matter tracts, tract-specific effects may be secondary to a global impact of age on white matter health. Furthermore, this global age effect could result in...
Healthy aging in rats is associated with a decline in the ability to inhibit maladaptive responses, but not in measures of self-control by delayed gratification
CONCLUSION: Across these experiments we show that the impact of aging on cognitive health is not unitary, in that aging negatively impacts the adaptation of motor actions independent of self-control.
Risk factors and mediation role of sleep quality for depression in cognitively frail older adults: a cross-sectional study
CONCLUSION: Dependence in ADL, loneliness, and poor sleep quality are potential risk factors of depression for cognitive frailty in aging adults. Moreover, sleep quality was found to mediate the relationship between ADL dependence and depressive symptoms.
Multiple roles for a mitochondrial enzyme
The enzyme arginase-II has an important role in cardiac aging, and blocking it could help hearts stay young longer.
An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility
Retrotransposons, multi-copy sequences that propagate via copy-and-paste mechanisms, occupy large portions of eukaryotic genomes. A great majority of their manifold copies remain silenced in somatic cells; nevertheless, some are transcribed, often in a tissue-specific manner, and a small fraction retains its ability to mobilize. While it is well characterized that retrotransposon sequences may provide cis-regulatory elements for neighboring genes, how their own expression and mobility are...
Targeting CA2 Perineuronal Nets Restores Recognition Memory and Theta Oscillations in Aged Mice
Remembering familiar versus novel stimuli is fundamental to survival, but it is compromised in several neurodegenerative disorders where aging is a key factor. Although the components of the extracellular matrix (ECM) have been suggested to be implicated in memory maintenance, the mechanistic and behavioral roles of ECM during the aging process remain unclear. Here, we employed an accelerated mouse model of aging to elucidate the causal link between ECM dynamics and recognition memory during...
Rate of brain aging associates with future executive function in Asian children and older adults
Brain age has emerged as a powerful tool to understand neuroanatomical aging and its link to health outcomes like cognition. However, there remains a lack of studies investigating the rate of brain aging and its relationship to cognition. Furthermore, most brain age models are trained and tested on cross-sectional data from primarily Caucasian, adult participants. It is thus unclear how well these models generalize to non-Caucasian participants, especially children. Here, we tested a previously...
Molecular hydrogen therapy: A "democratic" emerging strategy against aging and age-related diseases
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: evaluation of intrinsic capacity changes in humans, mice, and killifish to explore the biology of aging
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...
Senescence-resistant human mesenchymal progenitor cells counter aging in primates
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...
Association between social participation and medical care utilization among rural older adults in China: a longitudinal study based on the CLHLS (2011-2018)
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 genes networks in Alzheimer's disease: correlations with neuropathology and cognitive decline
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...
Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength
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...
SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging
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...
Senescence in cancer
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...
Exercise alters transcriptional profiles of senescence and gut barrier integrity in intestinal crypts of aging mice
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...
Reply to Ferraro et al.: Breed-and-feed reflects inevitable trade-offs between individual longevity and population sustainability
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