Aging & Longevity

Age-related thymic involution, leading to reduced T cell production, is one of the major causes of immunosenescence. This results in an increased susceptibility to cancers, infections, and autoimmunity and in reduced vaccine efficacy. Here, we identified that the receptor activator of nuclear factor κB (RANK)-RANK ligand (RANKL) axis in the thymus is altered during aging. Using a conditional transgenic mouse model, we demonstrated that endothelial cells depend on RANK signaling for their...

Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals....

The metabolism of branched-chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched-chain amino acids (BCAAs). Three metabolites of BCAAs isovalerate, 2-methylbutyrate, and isobutyrate were used to treat D-gal induced aging mice. The results showed that these treatments could delay aging in mice by providing health benefits in reducing oxidative stress and...

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a...

While HIV infection and clonal hematopoiesis (CH) have been linked with inflammatory dysregulation and an increased risk of aging-related comorbidities, their relationship with clinical geriatric syndromes has not been well defined. In the Age-related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE) study (NCT04641013), we measure associations between HIV and CH and geriatric syndromes. Of 345 participants (176 with HIV and 169 without HIV), 23% had at least one mutation associated...

Aging involves metabolic changes that lead to reduced cellular fitness, yet the role of many metabolites in aging is unclear. Understanding the mechanisms of known geroprotective molecules reveals insights into metabolic networks regulating aging and aids in identifying additional geroprotectors. Here we present AgeXtend, an artificial intelligence (AI)-based multimodal geroprotector prediction platform that leverages bioactivity data of known geroprotectors. AgeXtend encompasses modules that...

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The prevalence of hypertension increases with age and is the leading modifiable risk factor for cognitive impairment and dementia. At present, the neural mechanisms promoting hypertension across the lifespan are incompletely understood. Using the Sprague-Dawley (SD) rat as a model of normal aging, we hypothesized (1) blood brain barrier (BBB) disruption and neuroinflammation in the paraventricular nucleus (PVN) of the hypothalamus enhances sympathetic tone and contributes to age-dependent...

CONCLUSION: The inclusion of content such as spiritual needs and preventive healthcare services in undergraduate nursing curriculum is important in developing graduates that provide quality nursing care for older adults in Ghana. Additionally, the use of teaching approaches such as stand-alone courses, and clinical simulations can contribute significantly towards dispelling misconceptions about ageing and provide a deeper understanding of the care needs of older adults among nursing graduates in...

During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin...

Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young...

CONCLUSION: Our study established a linear relationship between CVAI and mortality risk among community-dwelling older adults, with higher CVAI levels associated with a lower risk of all-cause mortality. These findings highlight the potential importance of visceral adiposity in predicting mortality risk in community-dwelling older adults.

CONCLUSION: The proposed frailty phenotype classification differs from the existing frailty measures in its ability to distinguish the corresponding phenotypes underlying various health consequences. Governments may develop strategies based on frailty phenotypes to mitigate adverse health consequences.

CONCLUSIONS: Individuals who reported more memory complaints had higher levels of biomarkers of neurodegeneration and a faster rate of cognitive decline, suggesting that SMCs may be valuable for identifying people at high risk of cognitive impairment.

Studying the fecal microbiota of wild baboons helps provide new insight into the factors that influence biological aging.

The Damaraland mole-rat (DMR; Fukomys damarensis) is a long-lived (~ 20 years) Bathyergid rodent that diverged 26 million years ago from its close relative, the naked mole-rat (NMR). While the properties of NMR cultured fibroblasts have been extensively studied and have revealed several unusual features of this cancer-resistant, long-lived species, comparative DMR studies are extremely limited. We optimized conditions for successfully culturing primary DMR skin fibroblasts and also established...

The accumulation of senescent cells can lead to tissue degeneration, chronic inflammatory disease and age-related tumorigenesis. Interventions such as senolytics are currently limited by off-target toxicity, which could be circumvented by instead enhancing immune-mediated senescent cell clearance; however, immune surveillance of senescent cells is often impeded by immunosuppressive factors in the inflammatory microenvironment. Here, we employ a chimeric peptide as a 'matchmaker' to bind to the...

CONCLUSION: In older adults with SBP < 130 mmHg, DBP values 80-89 mmHg were not associated with higher risk of CV organ damage, events or mortality.

CONCLUSIONS: These findings suggest that individuals who participated more frequently in more leisure activities had a higher chance of the maintenance of successful aging in older adults. Encouraging older people to frequently participate in a greater variety of leisure activities may be an effective way to maintain successful aging over time.