Aging & Longevity

CONCLUSIONS: The cancer-related identity in long-term PCa survivors of advanced old age varies widely. Especially negatively connoted cancer-related identities reflect the subjective disease experience, the overall health status, and the lack of a social support system. Even years after the primary diagnosis and treatment, assessment of the cancer-related identity can identify men who are affected most by their cancer experience and might need further psycho-oncological assistance.

Air pollution is a major global health threat, with exposure exhibiting substantial heterogeneity across and within regions. While disparities in air pollution exposure by income groups are well documented, how these inequalities translate into differential burdens of pollution-attributable premature mortality remains understudied. We utilize high-resolution estimates of secondary air pollutants, combined with income data, to investigate the relationship between global air pollution-attributable...

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Manipulating the neuronal pathway responsible for the hypoxic stress response in the worm C. elegans leads to an increase in lifespan.

INTRODUCTION: Alzheimer's disease and other dementias (ADOD) represent a growing global health crisis driven by the rapid aging of the population. Using data from the 2021 Global Burden of Disease (GBD) study, we provide updated global and national estimates of the ADOD burden from 1990 to 2021, quantify key risk factors, and offer evidence to guide resource allocation and prevention strategies.

CONCLUSION: CVD risk is associated with global and regional brain aging, with specific cortical regions demonstrating greater vulnerability to CVD risk burden than others. These findings highlight the added value of regional BAG analyses, which reveal heterogeneity in aging patterns not captured by global estimates alone and may clarify vascular contributions to brain aging.

With the advancement of combination antiretroviral therapy (ART), over 50% of people with HIV (PWH) in the United States are now over the age of 50. A hallmark of the aging immune system is a progressive dysfunction of both the innate and adaptive immune responses, often characterized by clonal expansion of memory T cells. However, the impact of age-related immune dysfunction on HIV/SIV reservoir dynamics remains understudied. We hypothesized that age-associated clonal expansion of memory T...

Aging is the strongest risk factor for cognitive decline and Alzheimer's disease (AD), yet the mechanisms underlying brain aging and their modulation by pharmacological interventions remain poorly defined. The hippocampus, essential for learning and memory, is particularly vulnerable to metabolic stress and inflammation. Canagliflozin (Cana), an FDA-approved sodium-glucose co-transporter 2 inhibitor (SGLT2i) for type 2 diabetes, extends lifespan in male but not female mice, but its impact on...

We investigated the roles of Rac guanine-nucleotide exchange factor (Rac-GEF) P-Rex1 in glucose homeostasis using Prex1^(-/-) and catalytically inactive Prex1^(GD) mice. P-Rex1 maintains fasting blood glucose levels and insulin sensitivity through its Rac-GEF activity but limits glucose clearance independently of its catalytic activity, throughout aging. Prex1^(-/-) mice on a high-fat diet are protected from diabetes. The increased glucose clearance in Prex1^(-/-) mice may stem in part from...

Zinc plays a critical role in memory, learning, and neuronal function, with dysregulation increasingly implicated in neurodegenerative diseases such as Alzheimer's disease (AD). This study aimed to investigate whether changes in the expression of zinc transporter proteins, ZnT3 and ZIP3, in the retina mirror those in the brain, and to explore their potential as non-invasive biomarkers for early AD detection. Immunofluorescence and Western blotting were used to assess ZnT3 and ZIP3 expression in...

Predictors of immune checkpoint inhibitor response in cancer remain elusive. From a previous phase 2 neoadjuvant immunotherapy window-of-opportunity study, we present the single-cell RNA and T cell receptor (TCR) sequencing analysis of 57 pre- and post-treatment tumor biopsies from head and neck cancer patients treated with durvalumab (anti-PD-L1) alone or with tremelimumab (anti-CTLA-4), identifying key cellular and molecular predictors of immune checkpoint inhibitor (ICI) response. Malignant...

BACKGROUND: Despite the success of immune modulation in the treatment of relapsing multiple sclerosis, disability progression is a major problem driven by multiple mechanisms. Comorbidities (eg, vascular risk) and ageing are thought to augment these neurodegenerative pathologies. In the phase 2b MS-STAT trial of simvastatin (80 mg) versus placebo in secondary progressive multiple sclerosis (SPMS), the adjusted difference in brain atrophy rate between groups was -0·254% per year: a 43% reduction....

CONCLUSION: The ABC community program might be a scalable collaborative dementia care model targeting socially vulnerable people living with dementia.

Cells use information about their environments and internal states to decide whether to proliferate, differentiate, or enter non-proliferative states such as quiescence and senescence. But how do they integrate this information to make unambiguous decisions? Here, we describe how the interaction between two independent condensates, P-bodies and Whi3-dependent condensates, enables individual yeast cells to integrate information about their biological age and the presence of potential mates during...

Spaceflight provides a unique environment that profoundly influences stem cell biology. Experiments aboard the International Space Station (ISS) and in simulated microgravity have revealed altered stem cell proliferation, differentiation, and stress responses, unveiling possibilities for modeling impacts of spaceflight and harnessing microgravity for biomanufacturing. Stem cell-derived organoids and tissue models flown in space are yielding insights into development, disease, and aging...

Aging is the main determinant of chronic diseases and mortality, yet organ-specific aging trajectories vary, and the molecular basis underlying this heterogeneity remains unclear. To elucidate this, we integrated genomic, epigenomic, transcriptomic, proteomic, and metabolomic data, employing post-genome-wide association study methodologies to systematically investigate the molecular mechanisms of nine organ-specific aging clocks and four blood-based epigenetic clocks. We uncovered genetic...

CONCLUSIONS: The findings of this cross-sectional study suggested that differential marital status has a variable impact on the risk of developing age acceleration, with significant gender differences. All indications are that men benefit more from marriage in the aging process, which is food for thought.

Mitochondrial dysfunction is a central driver of cellular senescence, a core hallmark of aging. While intrinsic mechanisms have been extensively reviewed, this article offers a novel paradigm by emphasizing the critical role of interorganellar communication in mitochondria-mediated senescence. We present a systematic dissection of the molecular mechanisms underlying functional crosstalk between mitochondria and key organelles, including the endoplasmic reticulum (ER), lysosomes, and peroxisomes....

Mitochondrial protein homeostasis (proteostasis) keeps the mitochondrial proteome functional. Thus, proteostasis is essential for mitochondrial activity and overall cellular functions, and a reduction in its function corresponds with diseases and aging in humans. Recent studies in various model organisms highlight components and mechanisms of mitochondrial proteostasis from biogenesis, through assembly, to turnover. Key findings include the identification of new components and mechanistic...

Creative experiences may enhance brain health, yet metrics and mechanisms remain elusive. We characterized brain health using brain clocks, which capture deviations from chronological age (i.e., accelerated or delayed brain aging). We combined M/EEG functional connectivity (N = 1,240) with machine learning support vector machines, whole-brain modeling, and Neurosynth metanalyses. From this framework, we reanalyzed previously published datasets of expert and matched non-expert participants in...