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Inflamm-aging is widely considered a hallmark of aging, yet emerging evidence challenges its universality. Here, we re-examine inflamm-aging through an eco-evolutionary lens, underlining its context dependence across biological scales. Combining mechanistic, evolutionary, comparative, anthropological, genetic, and environmental evidence, we show how fundamental inflammatory mechanisms are integrated and regulated in diverse biological contexts, representing a suite of flexible stress responses....

This study examines how neighborhood social cohesion and physical disorder, measured at baseline and as change over time, are associated with multiple chronic conditions (MCCs) among older adults and whether these associations vary by race/ethnicity. Using 6 years of data from the National Health and Aging Trends Study (2015-2021), mixed-effects Poisson regression models were applied to a sample of 3,389 community-dwelling older adults. Higher social cohesion at baseline and increases in...

CONCLUSION: intergenerational support from adult children significantly enhances the intrinsic capacity of older adults by promoting social engagement and maintaining functional ability. To advance healthy and active aging, policy efforts should adopt a function-oriented approach that strengthens both family-based support systems and community care infrastructure, while fostering cross-generational resource sharing and coordinated support.

The "gut-brain axis" is an emerging target in Alzheimer's disease (AD), although its immunological features remain poorly understood. Using single-cell RNA sequencing, coupled to extensive spectral-tuning flow cytometry validation of the colon immune compartment in the 5XFAD amyloid-β mouse model, we found several AD-associated changes including in B/plasma cell activity. Notably, levels of CXCR4^(+) antibody-secreting cells are reduced in 5XFAD colons. This change corresponds with accumulating...

Alzheimer's disease (AD) is marked by neuroinflammation, neurodegeneration and cognitive decline, with emerging evidence highlighting the critical roles of cytokines and chemokines in its pathogenesis. Regulated cell death is a highly structured and meticulously coordinated series of molecular and signalling processes involving gene expression and protein activity. This mechanism is essential for normal developmental processes and the preservation of tissue homeostasis. Abnormal regulation of...

Age-related hearing loss (ARHL) has emerged as a significant and potentially modifiable risk factor for neurodegenerative disorders, including Alzheimer's disease. A growing body of evidence links ARHL to structural and functional changes in the brain, with implications for cognitive decline and dementia onset. However, both ARHL and dementia are multifactorial conditions shaped not only by biological mechanisms but also by broader social determinants of health. Inequities in access to hearing...

Amyloid-β (Aβ), a key driver of Alzheimer's disease (AD) pathogenesis, possesses diverse harmful and clearance-resistant structures that present substantial challenges to therapeutic development. Here, we demonstrate that modulating Aβ morphology, rather than Toll-like receptor 2 (TLR2)-dependent microglia activation, is essential for effective phagocytosis of Aβ species by microglia. By developing a bifunctional mechanistic probe (P2CSKn) designed to remodel Aβ and activate TLR2, we show it...

Hallmarks of sensorineural hearing loss are elevated hearing thresholds and defects in temporal auditory processing, the former being often caused by outer hair cell (OHC) damage, and the latter by the loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons. In the well-studied CBA/CaJ mouse strain, these impairments are disconnected, IHC synaptopathy preceding OHC loss. We have investigated the relationship between IHC synaptopathy and OHC loss in the C57BL/6J (B6) and ICR...

CONCLUSIONS AND IMPLICATIONS: Northern and Western Europe show greater functional independence in late life than Eastern and Southern Europe. Several factors were significantly associated with independent functioning, including physical activity, polypharmacy, absence of multimorbidity, absence of depressive symptoms, absence of loneliness, unimpaired cognition, lower age, and male gender. Our results should be considered to target interventions aiming at healthy aging in these individuals.

Age-related hearing loss (ARHL) has emerged as a significant and potentially modifiable risk factor for neurodegenerative disorders, including Alzheimer's disease. A growing body of evidence links ARHL to structural and functional changes in the brain, with implications for cognitive decline and dementia onset. However, both ARHL and dementia are multifactorial conditions shaped not only by biological mechanisms but also by broader social determinants of health. Inequities in access to hearing...

BACKGROUND: Systematic analyses of global health trends can provide an accurate narrative of progress and challenges. We analysed the impact of changing age-specific mortality (epidemiology) and age structure (demography) on crude death rates (CDRs) and causes of death with large or rising mortality to inform the third Lancet Commission on Investing in Health.

CONCLUSIONS: A stronger risk of total mortality was found when worse SWB and unhealthy lifestyle occurred together, suggesting that a comprehensive approach to healthy lifestyle and SWB might be a potential strategy to improve longevity.

Aging is closely related to the decline of male reproductive endocrine function, which is manifested as insufficient testosterone production. It is well known that stem cell pool stability is crucial for maintaining tissue function. However, the relationship between aging and the stem Leydig cell (SLC) pool homeostasis remains unclear. Here, we demonstrate that extracellular matrix (ECM) stiffness increases in aging testes, and SLC pool homeostasis is imbalanced. Mechanistically, high ECM...

The longitudinal directionality between depressive symptoms and biological aging acceleration has yet to be thoroughly investigated. This study included 5442 Chinese adults aged 45-80 years from the 2011 and 2015 survey waves of China Health and Retirement Longitudinal Study. Multiple biomarker-based biological age was estimated using the Klemera and Doubal method, and biologically older was defined as biological age larger than chronological age. Depressive symptoms were identified using a...

Neuropathic pain (NP) is a complex pain disorder that constitutes a significant problem in the aging population, impacting quality of life and everyday functioning. In the quest to develop effective treatments, much research effort has been made to understand brain activity in people with NP, revealing a number of disordered electroencephalogram (EEG) patterns. This information can then be used to inform neurofeedback therapy, a novel approach that involves volitionally training brain activity...

Lactate is the end product of anaerobic glycolysis. Its functions in the central nervous system have garnered increasing attention as new roles continue to emerge. Beyond serving as an energy source and a substrate for gluconeogenesis, lactate also functions as a signaling molecule that regulates diverse cellular activities. Recent studies have demonstrated that lactate contributes to protein lactylation-a novel posttranslational modification-and plays a crucial role in metabolic reprogramming....

Early detection of Alzheimer's disease remains complex and costly despite advancements in neurobiological markers. We propose an innovative approach based on the topological and kinetic analysis of verbal exchanges to distinguish patients from healthy individuals. Without requiring full transcription, we leverage a convolutional network capable of identifying discursive patterns indicative of cognitive impairments. Our experiments, conducted with 80 participants, demonstrate performance levels...

Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer's disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and...

CONCLUSIONS: We believe that the results of our review indicate accelerated epigenetic ageing in people living with HIV compared to uninfected individuals. There is a need for further research, which will analyse material from different tissues and take into account a number of biomarkers and the mentioned confounding factors. Studies considering the impact of individual classes of antiretroviral drugs, the age of the patient at the time of HIV diagnosis, and the timeliness of diagnosis on...

Second-order conditioning (SOC) enables animals to form associations between stimuli without direct reinforcement. In this study, we present a behavioral analysis pipeline that combines a light-tone SOC paradigm in mice with tools such as DeepLabCut, Keypoint-MoSeq, and DeepOF to evaluate responses across sex and age. Our results show that responses to the second-order stimulus (CS(2)) specifically stem from its association with the first-order stimulus (CS(1)). While CS(1) triggers behavioral...