Aging & Longevity

CONCLUSIONS: Incorporating frailty assessment may enhance risk stratification and clinical decision-making in older adults with cancer.

Deficits in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) may indicate vulnerability to vascular dysfunction and cognitive impairment. Prior findings on age-related change in CVR are mixed, and no studies to date have investigated age group differences in spontaneous CVR (sCVR) at rest. The present study compared whole brain and regional sCVR at rest between 24 healthy younger adults (ages 18-34) and 163 cognitively unimpaired older adults (ages 55-87). Relative to younger...

Isolated atrial amyloidosis (IAA) is a localized cardiac disorder characterized by atrial natriuretic peptide (ANP) amyloids deposition in the atria, linked to aging and atrial fibrillation (AF). While monomeric ANP regulates blood pressure, its dimeric form is associated with cardiovascular conditions, including AF. The mechanistic link between ANP aggregation, IAA, and AF remains unclear. Here, we present the first high-resolution structural characterization of ANP fibrils extracted from AF...

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At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth¹, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto's paradox². Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale...

The generation and maintenance of immunity is a dynamic process that is dependent on age^(1-3). Here, to better understand its progression, we profiled peripheral immunity in more than 300 healthy adults (25 to 90 years of age) using single-cell RNA sequencing, proteomics and flow cytometry, following 96 adults longitudinally across 2 years with seasonal influenza vaccination. The resulting resource generated a single-cell RNA-sequencing dataset of more than 16 million peripheral blood...

Senescent cells drive age-related tissue dysfunction via the induction of a chronic senescence-associated secretory phenotype (SASP). The cyclin-dependent kinase inhibitors p21^(Cip1) and p16^(Ink4a) have long served as markers of cellular senescence. However, their individual roles remain incompletely elucidated, particularly in vivo. Thus, we conducted a comprehensive examination of multiple single-cell RNA sequencing datasets spanning both murine and human tissues during aging. Our analysis...

To assess associations between blood nicotinamide adenine dinucleotide (NAD) levels and laboratory parameters at baseline and after 60 days of nicotinamide mononucleotide (NMN) supplementation. Post hoc analysis of a randomized, double-blind, clinical trial of daily NMN (300, 600, or 900 mg) or placebo in healthy middle-aged participants. Among the 80 participants (49.4 ± 6.8 year), the baseline NAD was 7.21 [5.5, 10.6] nM. Every 1 nM higher baseline NAD level was associated with 0.24% (95%CI:...

DunedinPACE quantifies the pace of biological aging. No study has examined its association with cardiorespiratory fitness (CRF). Additionally, the physiologically relevant CRF thresholds associated with slow aging remain unclear. The purpose of this study was to investigate the association between CRF and the pace of epigenetic aging, as measured by DunedinPACE, and to identify a CRF threshold indicative of slower biological aging. Here, we analyzed data of 144 older men (aged 65-72 years)...

Experiments on yeast show that the nuclear pore complex has a central role in the loss of chromosomes associated with aging.

In many organisms, aging is a clear risk factor for chromosome missegregation, the main source of aneuploidy. Here, we report that old yeast cells lose chromosomes by partitioning them asymmetrically to their daughter cells together with the pre-existing (old) spindle pole body (SPB, centrosome equivalent in yeast). Strikingly, remodelling of the nuclear pore complex (NPC) and the displacement of its nuclear basket triggered these asymmetric chromosome segregation events. Simultaneously, nuclear...

CONCLUSIONS: Evidence shows a lack of structured long-term care policy in sub-Saharan Africa. Given the increasing demand for long-term care, there is an urgent need for policies that address factors affecting quality of life and ensure better care for older people in these facilities. A protocol for the scoping review was preregistered on the Open Science Framework Registry on 9th September 2023 (https://osf.io/xm8r5/).

Alpha-1 antitrypsin (AAT) deficiency in younger people is well characterized, but the effects of elevated AAT levels in older age are unclear. We examined the effect of elevated AAT levels and mortality in a longitudinal cohort of older adults, alongside high-sensitivity C-reactive protein (hs-CRP) levels. This post hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial included 11,879 adults aged ≥ 70 years without prior cardiovascular disease, dementia or life-limiting...

Social isolation and loneliness are growing public health concerns worldwide; however, the independent and combined associations of change in social isolation and loneliness with mortality are yet to be elucidated. This study aimed to investigate these associations among older adults. This cohort study used data from the Chinese Longitudinal Healthy Longevity Survey, which recruited participants from 2002 to 2011. A total of 8,956 participants aged 65 years and older were included. We used data...

Brown adipose tissue (BAT) protects against obesity, diabetes, and cardiovascular disease. During BAT activation, macroautophagy is inhibited, while chaperone-mediated autophagy (CMA) is induced, promoting thermogenic gene expression, adipokine release, oxidative activity, and lipolysis. Aging reduces BAT function and lowers levels of LAMP2A, the rate-limiting CMA component. Pharmacological CMA activation restores BAT activity in aged mice. To explore the CMA's role in BAT, we generated...

Genome instability is a major factor contributing to cellular senescence. The rRNA gene (rDNA), a repetitive sequence array, is a highly unstable region of the genome. In budding yeast, this instability induces senescence and shortens the lifespan. While the importance of rDNA stability in the aging process is well recognized, the mechanism driving rDNA instability in old cells remains unclear. Using effective methods to isolate old cells in budding yeast, our observations suggest that...

CONCLUSION: The results demonstrate a notable correlation between exposure to heavy metals, specifically lead and cadmium, and the incidence of frailty in U.S. adults aged over 20 years, with a more substantial impact observed in female participants.

Mitochondria play a crucial role in cellular energy metabolism and homeostasis and are strongly implicated in aging and age-related diseases. The outer mitochondrial membrane protein voltage-dependent anion channel (VDAC) plays multiple roles in mitochondrial homeostasis, including transport of metabolites, ATP, and Ca^(2+) Dysregulation of VDAC levels has been associated with cancer, neurodegeneration, metabolic disorders, and aging. Previously, we demonstrated that elevated VDAC-1 levels in...