Aging & Longevity

mTORC1 activity is increased in muscle with aging and is implicated as a potential driver of age-related declines in muscle health. While pharmacological inhibition of mTORC1 improves lifespan and healthspan, it remains unclear whether chronic activation of mTORC1 is sufficient to accelerate aging in skeletal muscle. We aimed to address this question using an inducible model of muscle-specific knockout of Depdc5, which encodes the protein DEP domain containing 5 (DEPDC5), a negative regulator of...

A coordinated response to stress is crucial for promoting the short- and long-term health of an organism. The perception of stress, frequently through the nervous system, can lead to physiological changes that are fundamental to maintaining homeostasis. Activating the response to low oxygen, or hypoxia, extends healthspan and lifespan in Caenorhabditis elegans. However, despite some positive impacts, negative effects of the hypoxic response in specific tissues prevent translation of their...

ObjectivesThis study explores the relationship between marital status, living arrangements, and aging well among Chinese adults aged 50 and older.MethodsUsing data from the China Family Panel Studies (CFPS), we developed a multidimensional measure of aging well (physiological, functional, cognitive, psychological, and subjective). Analysis was based on a five-category typology of marital and living arrangements.ResultsA clear hierarchy emerged in the findings: married individuals co-residing...

The immune-fibrotic axis functions as a vicious feedback loop where age-related chronic, low-grade systemic inflammation (inflammaging) drives maladaptive tissue repair and fibrosis, while senescent fibrotic cells in turn amplify systemic inflammation. In the aging heart, immune dysregulation and fibroblast activation drive tissue scarring and stiffening and a higher risk of heart failure and vascular disease. To identify cardiac regions and cell types affected with age, we monitored...

Rapamycin, an mTOR inhibitor, continues to be investigated for hypothesized physiological, disease prevention, and longevity benefits, but few studies have been conducted in humans. Using US national organ transplant registry data, one of the largest real-world datasets examining chronic rapamycin exposure in humans, we compared the Kaplan-Meier survival age distribution of 4885 kidney transplant recipients prescribed rapamycin compared to 6589 recipients not prescribed rapamycin. Recipients...

Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers, distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS...

CONCLUSION: Among Chinese adults aged ≥ 65 years, the cMIND diet Q2 group was significantly associated with BADL disability, while the overall cMIND diet was significantly associated with IADL disability, supporting its potential role in promoting functional independence during aging.

Dietary restriction (DR) extends lifespan in animals and plants, but its evolutionary causes are elusive. The prevailing explanation is that DR prolongs life by shifting resources from reproduction to somatic maintenance. To test this idea in Caenorhabditis elegans we developed an experimental paradigm that tricks nematodes into increasing their reproductive effort under DR via food odour cues. Although DR improved survival, experimentally increased reproduction under DR did not reduce either...

To define the role of pyroptotic macrophage-derived extracellular vesicles (EVs) in diminished ovarian reserve (DOR) and to elucidate whether EVs-mediated transfer of miR-103a-3p drives mitochondrial dysfunction in granulosa cells. Single-cell RNA sequencing data from public GEO datasets were analyzed to characterize pyroptosis-associated features in ovarian macrophages across age groups. EVs were isolated from pyroptotic macrophages and applied to granulosa cells (KGN) to assess mitochondrial...

Sirtuins are a family of enzymes that regulate cell homeostasis through pathways impacting genomic stability, mitochondrial function, cellular senescence, inflammation, and autophagy. In the skin, these pathways protect against extrinsic insults, maintain keratinocyte stem cells, and contribute to the overall structure and integrity of the skin barrier. Sirtuins decline with chronologic age, with UV exposure also impacting their activity, resulting in a loss of this homeostasis. There are 13...

CONCLUSION: This study highlights that both a high baseline TyG index and a persistently elevated TyG trajectory are strongly associated with increased all cause mortality among older adults in southwestern China. Regular health check-ups and early interventions targeting elevated TyG levels may help promote longevity and improve health outcomes in this population.

Age-related skeletal muscle decline (sarcopenia) contributes to frailty and mortality, yet how sex influences muscle aging and dietary interventions remains unclear. Using the short-lived vertebrate Nothobranchius furzeri, we investigated how sex and intermittent fasting (IF) interact to regulate lifespan and skeletal muscle aging. We establish an IF regimen that extends lifespan in both males and females, despite trade-offs including reduced growth and reproductive output. Importantly, IF...

In a study recently published in Nature, Belk et al.¹ use somatic mutations to demonstrate that bone marrow-derived cells enter the aging human brain and resemble microglia. The aged microglial compartment may therefore have a substantial hematopoietic contribution, and its clonal composition may prove important for stem-cell-based microglial replacement.

CONCLUSIONS: Anthropometric adiposity measures, particularly BMI, WC, and WHtR, were more consistently related to MRI-derived brain age gap than to brief cognitive screening performance in a cohort of middle-aged and older adults. These findings describe cross-sectional associations with older predicted brain age, especially at higher adiposity levels.

CONCLUSIONS: These data suggest that circulating levels of miR-181b-3p, miR-490-5p, and miR-511-5p might serve as markers of frailty in old people with CVD and that miR-181b-3p and miR-490-5p might be functionally linked to the pathophysiology of the syndrome through their effects on cellular senescence and inflammation.

The Mexican cavefish, Astyanax mexicanus, is a powerful evolutionary model for investigating how adaptation to extreme environments reshapes vertebrate physiology. Multiple cave populations have independently evolved under subterranean conditions, acquiring traits including insulin resistance, persistent hyperglycaemia, increased adiposity, altered sleep patterns, hypoxia tolerance and extensive metabolic reprogramming. Despite these differences, cavefish exhibit lifespans comparable to those of...

In older adult gait research, "healthy" often characterizes study samples yet is typically defined by absence of disease rather than by positive characterization. This matters beyond gait, because such samples anchor reference values, mobility thresholds, and estimates of age-related decline. This scoping review examined how "healthy" is defined and operationalized in the older adult gait literature. Following PRISMA-ScR guidance, a search of Web of Science, SPORTDiscus, MEDLINE, and PubMed...

Resistant hypertension (RH) is increasingly linked to accelerated vascular aging and is particularly prevalent among older and obese individuals. Cellular senescence has emerged as a potential driver of vascular aging, but its contribution to RH remains unclear. We examined age and body mass index (BMI) in the WalkByLab cohort and assessed whether RH was associated with vascular features consistent with accelerated aging. Obesity-related transcriptomic datasets were integrated with a curated...

Pharmacotherapies for obesity and type 2 diabetes are increasingly being evaluated for their effects on cognition and brain health. Evidence from preclinical models, observational cohorts, and clinical trials has intensified interest, but findings remain mixed. A central challenge is to determine whether potential cognitive effects arise from direct actions on neural circuits, indirect consequences of improved cardiometabolic health, or both. This Review examines the evidence across...

CONCLUSION: This study shows for the first time age-related mitophagy impairment in human neurons, and confirms findings of age-related mitochondrial impairments in human neurons. By doing so, this study paves the way for more in-depth mechanistic studies that would allow for the identification of therapeutic targets for anti-aging treatment and in the context of age-associated neurodegenerative diseases.