Aging & Longevity

Evolutionary theory of aging predicts that women with increased reproductive effort live shorter lives, but evidence is inconsistent. These inconsistencies could be because environmental conditions influence how much a mother's life span is reduced when having more children, i.e., their life-span cost of reproduction. Using a structural equation measurement model, we compare how reproductive effort affects the life span of 4684 women exposed across different life stages, or not at all, to the...

Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer's disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD^(+)) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD^(+) enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD^(+) augmentation...

Endocytic recycling of transmembrane proteins is essential to cellular function. The intracellular domains of transmembrane proteins are frequently ubiquitylated, a modification that is recognized by adaptor proteins during clathrin-mediated endocytosis. Recent work suggests that transmembrane proteins compete for space within highly crowded endocytic structures, suggesting that enhanced internalization of one group of transmembrane proteins may come at the expense of others. Here, we show that...

Advancing age is accompanied by an accumulation of senescent T cells that secrete pro-inflammatory senescence-associated secretory phenotype (SASP) molecules. Gut-microbiota-derived signals are increasingly recognised as immunomodulators. In the current study, we demonstrated that ageing and the accumulation of senescent T cells are accompanied by a reduction in microbial-derived short-chain fatty acids (SCFAs). Culturing aged T cells in the presence of butyrate suppresses the induction of a...

Renin-angiotensin system (RAS) activation in heart failure (HF) increases circulating angiotensin II (AII). This increases blood pressure (BP) and promotes adverse ventricular remodeling that makes HF worse. Although human HF increases with age and differs between the sexes, preclinical studies have used young, mostly male animals. We investigated sex differences in AII-induced cardiac remodeling in aging C57BL/6 mice. Mice (≈16 months) were infused with AII (3 mg/kg/day; 6 weeks; osmotic...

Muscle mass and strength influence various age-related health outcomes, however their individual and joint associations with biological aging remain understudied. This study investigated the associations of muscle health with epigenetic aging based on DNA methylation in blood samples, among middle-aged and older adults. We analyzed data from 1,121 individuals from the 1999-2002 cycles of the National Health and Nutrition Examination Survey. Muscle mass was assessed using the appendicular...

Stressful events can lead to transient impairments in learning and memory, a phenomenon more pronounced in the elderly. As global life expectancy rises, the shift toward an aging society underscores the urgent need for effective preventive strategies against stress-induced cognitive dysfunction. Elucidating its pathogenesis is essential for developing neuroprotective interventions and mitigating medical and societal impacts. In this study, male C57BL/6 mice aged 2 and 18 months were subjected to...

There is growing evidence that perceptual difficulties associated with age-related hearing loss are not solely due to cochlear damage and are exacerbated by central nervous system changes. We examined electrophysiological (EEG) responses to clicks and diffusion kurtosis imaging in 49 older (29 female) and 26 younger (20 female) adults to determine the extent to which auditory nerve (AN) deficits in older adults contributed to functional and structural changes throughout the auditory system....

Immunotherapy-based combination approaches have improved treatment efficacy in advanced non-small cell lung cancer (NSCLC), but progressive disease remains a challenge. Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor approved for myelopreservation in extensive-stage small cell lung cancer (ES-SCLC). Our results demonstrate that trilaciclib has antitumor potential in NSCLC without significant toxicity. It reprograms the tumor immune microenvironment by primarily increasing antitumor...

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Aging is associated with significant alterations in the composition of the gut microbiota, including decreased microbial diversity. These changes are accelerated by lifestyle factors, such as sedentary behavior, which tends to increase with age. Although the role of physical activity in preventing age-related functional decline has been widely recognized in recent years, its long-term influence at different intensity levels on gut microbial composition in older adults remains unclear. In this...

Early diagnosis and noninvasive monitoring of neurological disorders require sensitivity to elusive cellular-level alterations that occur much earlier than volumetric changes observable with the millimeter-resolution of medical imaging modalities. Morphological changes in axons, such as axonal varicosities or beadings, are observed in neurological disorders, as well as in development and aging. Here, we reveal the sensitivity of time-dependent diffusion MRI (dMRI) to the structurally disordered...

Epigenetic and omics-based clocks have provided invaluable tools to quantify aging, yet these clocks do not provide direct readouts of aging in real-time in living systems. As methylation changes in nucleolar ribosomal DNA are reliably associated with aging and cellular senescence, we hypothesized that shifts in rRNA species could be leveraged to generate image-based clocks using selective dyes. Here we engineer sensitive and photostable hybrid polymethine dyes selective for rRNA. We present a...

CONCLUSIONS: These findings enhance our understanding of the association between chronic diseases and depressive symptoms and provide important insights that can guide policy-makers and practitioners in addressing the psychological challenges faced by older adults with chronic diseases.

The spatial heterogeneity of halogen distribution in perovskite thin films represents a critical factor currently limiting both the power conversion efficiency and stability of solar cells. We identified pronounced through-film inhomogeneity in chlorine distribution in formamidinium lead iodide films, with the generally used additive methylammonium chloride. We demonstrated that incorporating alkali metal oxalates could effectively homogenize the chlorine distribution. These compounds underwent...

The HIV type 1 (HIV-1) accessory proteins Virion Infectivity Factor (Vif) and Viral Protein R (Vpr) are essential for efficient virus replication in vivo. Vif mediates degradation of host restriction factor APOBEC3G, while Vpr modulates the host cell proteome in ways that promote virion infectivity and viral gene expression. In cycling cells including CD4+ T cells, Vif and Vpr also severely impact cell cycle progression for reasons that remain unknown. Here, we combined live-cell imaging with...

CONCLUSION: Sarcopenic obesity is associated with an increased risk of falls among middle-aged and older adults, especially in longitudinal analyses. Age-stratified results suggest that the impact of SO on falls may be more pronounced in the middle-aged group. Our findings support the need for early identification and targeted interventions for individuals with SO to mitigate fall-related risks in aging populations.

The hippocampus, a brain region critical for memory, undergoes significant age-related changes at both the macroscopic and microstructural levels. This study investigates these changes using high-gradient diffusion MRI (dMRI) data analyzed in an unfolded hippocampal space. We applied the Soma and Neurite Density Imaging (SANDI) model to quantify microstructural alterations in 72 cognitively healthy participants aged 19-85 years, scanned on a 3 T Connectome MRI scanner with a maximum gradient...

Relationships between Alzheimer's disease (AD) pathologies in cognitively unimpaired adults and in vivo neurometabolic properties measured directly from the hippocampus, a vulnerable region early along the AD continuum, are not well-understood in the earliest stages of AD. In a 3T ¹H-MRS study, we assessed age and AD-related changes in estimates of absolute concentrations of neurometabolites in the right hippocampus. Participants included older adults (age range: 60-85, n = 19) primarily...

Long-term allergies can exhibit persistent concentrations of circulating immunoglobulin E (IgE). Here, we examined the lifespan of IgE antibody-secreting cells (ASCs) to determine whether the IgE that sustains allergies receives contributions from long-lived cells or relies more heavily on constant ASC production. In mouse aeroallergy, IgE ASCs localized to the lungs, mediastinal lymph nodes, spleen, and bone marrow (BM). IgE ASC production continued for months after allergen exposure ceased. We...