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The exposome, an individual's lifelong environmental exposure, profoundly impacts health. Somatic tissues undergo functional decline with age, exhibiting characteristic ageing phenotypes, including hair greying and cancer. However, the specific genotoxins, signals and cellular mechanisms underlying each phenotype remain largely unknown. Here we report that melanocyte stem cells (McSCs) and their niche coordinately determine individual stem cell fate through antagonistic, stress-responsive...

Translational research on cellular senescence has led to numerous early-phase clinical trials targeting senescent cells to treat, prevent or alleviate multiple disorders and diseases, including metabolic diseases and their comorbidities. Cellular senescence is a cell fate that occurs in response to stressors, including metabolic disruptions, and is one of the hallmarks (or pillars) of ageing. In their senescent state, cells cease proliferation and can develop a senescence-associated secretory...

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Morphological changes in the ageing eye impede oxygen delivery from the choroid to the outer retina causing tissue hypoxia, which activates a molecular response that adapts the transcriptomic fingerprint of the retina and retinal pigment epithelium (RPE). This response, orchestrated by hypoxia-inducible transcription factors (HIFs), leads to the production of pro-angiogenic factors and plays a critical role in the development and pathogenesis of age-related macular degeneration (AMD). To...

Trimethylamine N-oxide (TMAO) contributes to cardio-metabolic diseases, with hepatic flavin-containing monooxygenase 3 (FMO3) recognized as its primary source. Here we demonstrate that elevated adipocyte FMO3 and its derived TMAO trigger white adipose tissue (WAT) dysfunction and its related metabolic disorders in ageing. In adipocytes, ageing or p53 activation upregulates FMO3 and TMAO levels. Adipocyte-specific ablation of FMO3 attenuates TMAO accumulation in WAT and circulation, leading to...

CONCLUSION: Identification of older at risk of IC impairment in Cameroon may help tailor further policies for Healthy Aging taking into account available resources.

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...

Increasing evidence indicates skeletal muscle function is associated with cognition. Muscle-secreted protease Cathepsin B (Ctsb) is linked to memory in animals and humans, but has an unclear role in neurodegenerative diseases. To address this question, we utilized an AAV-vector-mediated approach to express Ctsb in skeletal muscle of APP/PS1 Alzheimer's disease (AD) model mice. Mice were treated with Ctsb at 4 months of age, followed by behavioral analyses 6 months thereafter. Here we show that...

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...

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...