Aging & Longevity

Attenuating protein synthesis promotes longevity in multiple species. However, numerous studies indicate that aging drives a decrease in protein synthetic capacity. These observations hint at potential, unexplored benefits of stimulating protein synthesis in old age. In this work, we focus on Maf1, a repressor of protein synthesis genes transcribed by RNA Polymerase (Pol) III, such as the 5S rRNA and tRNAs, and its role in aging. We show that the knockdown of Maf1 extends lifespan in Drosophila....

Macroautophagy/autophagy activation protects renal proximal tubular epithelial cells (PTECs) against acute kidney injury (AKI) induced by various challenges. The mechanism that regulates autophagy in PTECs, however, remains incompletely understood. Here, we report that VMP1 (vacuole membrane protein 1) plays an essential role in enabling PTECs to maintain high autophagic flow under AKI conditions. VMP1 in PTECs is strongly upregulated in AKI patients but not chronic kidney disease patients. The...

We know vanishingly little about how long-lived apes experience senescence in the wild, particularly with respect to their foraging behaviors. Chimpanzees use tools during foraging, and given the cognitive and physical challenges presented by tool use, tool-use behaviors are potentially at a heightened risk of senescence, though this has never been investigated in wild individuals. Accordingly, we sampled data from a longitudinal video archive that contained footage of wild chimpanzees using...

Aging is a complex biological process driven by genetic and immune-mediated mechanisms, yet the causal roles of immune-cell-specific gene regulation remain unclear. In this study, we integrate single-cell expression quantitative trait loci (sc-eQTL) data with Mendelian randomization (MR) and colocalization analyses to identify immune-mediated regulatory mechanisms and therapeutic targets for aging. Using data from 14 immune cell types, we systematically evaluated 8733 eGenes for causal effects...

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To understand observed spatial distributions of white-matter (WM) aging, developmentally driven theories termed "retrogenesis" have gained traction, positing that WM tract development order predicts order of declines, with later developing regions expected to deteriorate first, i.e., "last-in-first-out." Alternatively, regions that develop most rapidly may decline most rapidly in aging, i.e., "gains-predict-loss." The validity of such theories remains uncertain, partly due to lack of clarity in...

Sporadic Alzheimer's disease and some forms of frontotemporal lobar degeneration (FTLD-tau) are neurological disorders of later life where cognitive deficits follow from the progressive accumulation of microtubule-associated tau protein. Disease-related tau accumulation is marked by altered subcellular distribution and rearrangement of this natively unstructured protein into alternative conformational forms, including highly organized fibrillar assemblies. With a partial analogy to effects seen...

CONCLUSIONS: Depressive symptoms moderated the mediation of ADL on an indirect, negative correlation between DSI and SP. The findings contribute to existing knowledge by illustrating the fundamental mechanisms connecting DSI and SP. These Findings highlight the need for integrated interventions targeting both sensory impairment and mental health to mitigate SP decline in aging populations.

CONCLUSION: The study adds to a growing body of research demonstrating the feasibility and utility of online cognitive testing for reaching large cohorts of individuals across the adult lifespan. We report findings that mirror the existing literature on cognitive aging, but also provide unique insights into the trajectory of cognitive functioning. We discuss the benefits, challenges, and future promise of web-based testing.

CONCLUSIONS AND IMPLICATIONS: This study highlights how capitation rates positively influence care quality in nursing homes within the MLTSS context. The findings provide valuable insights for policymakers, health care administrators, and managed care organizations seeking to optimize care quality in MLTSS programs.

Patient genomics and mouse functional genetics have revealed that senescence is a barrier to metastatic progression of prostate cancer. Many efforts focus on eliminating senescent cells, whereas others aim to elucidate distinct characteristics that set them apart from normal and aging cells. Here, we discuss how exploration of the redox state of senescent cells could help define new markers and pro-oxidant vulnerabilities, drawing analogy to what is known about the redox sensitivity of...

Protective and risk factors can drive healthy or accelerated aging, with distinct environments modulating their effects. The impact of the exposome-the combined physical and social exposures experienced throughout life-on accelerated aging remains unknown. We assessed delayed and accelerated aging in 161,981 participants from 40 countries (45.09% female; mean age, 67.06; s.d., 9.85) by measuring biobehavioral age gaps (BBAGs), defined as the difference between estimated age from protective and...

Organ transplantation remains the sole definitive treatment for many forms of end-stage organ failure, yet donor organ shortages impose life-threatening delays for thousands of patients worldwide. Mechanical supports and dialysis provide only temporary respite, while lifelong immunosuppression poses additional risks-including infections, malignancies and considerable healthcare costs. Recent innovations hold promise for overcoming these barriers. Artificial intelligence tools increasingly guide...

Growing evidence suggests that the induction of cellular senescence in vascular cells is causally linked to the etiology of cardiovascular diseases. To investigate systematically the heterogeneity of senescent vascular cells in atherosclerosis, we used a high-fat diet and PCSK9 overexpression to induce atherosclerosis in a senescence reporter mouse model (p16-tdTomato^(+/-)) and performed single-cell RNA sequencing on whole aortas. Using the SenMayo and CellAge gene sets, we identified four...

Antler blastema progenitor cells (ABPCs) are a distinct population of skeletal mesenchymal stem cells found in regenerating deer antlers, with strong stemness and renewal capacity in vitro. Stem cell-derived extracellular vesicles (EVs) are emerging as potential therapeutic candidates that can mediate donor cells' beneficial effects. Here, we tested the effects of ABPC-derived EVs (EVs^(ABPC)) on aging in mice and rhesus macaques (Macaca mulatta). We identified a variety of unique factors in...

Age-related retinal degeneration, such as diabetic retinopathy and age-related macular degeneration, are major causes of blindness in modern society. Recent studies suggest that dysbiosis and intraocular translocation of bacteria from the blood circulation are critically involved in retinal degeneration. We hypothesise that the blood-retinal barrier (BRB) cells can protect the neuroretina from blood-borne pathogens by producing antimicrobial peptides (AMPs). The antimicrobial activity may...

Wound healing in old mice is characterized by disturbed tissue homeostasis, manifested by delayed immune cell infiltration and reduced growth factor secretion, leading to a delayed onset and prolonged duration of the inflammatory phase. The endocannabinoid system (ECS) is an important regulator of tissue homeostasis and cell migration and is also considered to be subject to aging processes, which may contribute to observable aging phenomena. Therefore, stimulating the aged ECS could represent a...

CONCLUSIONS: Probable sarcopenia, indicated by low HGS, was associated with an increased risk of cognitive impairment in older men, with risk consistent across BMI strata, including men living with probable sarcopenic obesity. Our findings have clinical relevance, suggesting that phenotypes comprising low muscle strength, in the presence of excess adiposity must not be overlooked and appropriate interventions explored to attenuate physical perturbations which could carry significance towards...

The combination of an increasing life expectancy and an increasing risk of fractures in the aging population collides with the still inadequate primary and secondary fracture prevention in Europe. Osteoporotic fractures have a major impact not only on morbidity, quality of life and mortality but also on healthcare costs. Therefore, an improvement of fracture prevention is warranted. Osteoanabolic drugs are particularly beneficial in patients with very high fracture risk and are recommended by...

CONCLUSIONS AND IMPLICATIONS: The CRPS is a scientifically robust tool to assess care risk perceptions in LTCFs. By identifying caregivers' risk awareness gaps, it supports targeted interventions and policy reforms for standardized safety audits to enhance dementia care quality and safety.