Aging & Longevity

Classical evolutionary theories of aging, including antagonistic pleiotropy (AP) and the disposable soma theory (DST), explain why aging exists but are often applied without considering how sex-specific reproductive strategies shape the forces of natural selection on survival. They do not explain why females consistently outlive males across taxa, despite their greater reproductive investment, or why in some contexts, such as eusocial queens, extraordinary fecundity is coupled with exceptional...

Hyperphosphorylation and aggregation of tau are pathological hallmarks of tauopathies. Mitochondrial dysfunction is also a common feature of tauopathies. The mechanistic link between tau abnormalities and mitochondrial dysfunction and its relationship to the physiological function of tau, however, is unclear. Here, we demonstrate that tau regulates mitochondrial reverse electron transport (RET), which produces excess reactive oxygen species (ROS), reduces the NAD^(+)/NADH ratio, and is activated...

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major challenges in critical care medicine, characterized by alveolar-capillary barrier disruption, excessive inflammation, and impaired gas exchange. With the growing aging population, aging has emerged as an important determinant of ALI/ARDS susceptibility, progression, and prognosis. Aging promotes pulmonary vulnerability through multiple interconnected mechanisms, including immune dysregulation,...

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Regular physical exercise is essential for promoting healthy aging and longevity. In older adults with varying physical and cognitive decline, optimising exercise interventions is crucial to maximise benefits. A promising approach to achieve this goal is by adjusting task demands to individual abilities in turn preventing over- or underloading their abilities. In the field of motor learning, it is currently unclear whether such an optimised training improves not only performance on the trained...

Longevity and stress resilience require precise coordination of gene expression programs across tissues. Here, we demonstrate that overexpression of the chromatin reader bet-1 specifically in neurons of Caenorhabditis elegans promotes organismal longevity and stress resistance via cell-nonautonomous signaling. Neuronal bet-1 elicits a neurotransmitter-dependent signal that activates the conserved stress-responsive transcription factor HSF-1 in the intestine, enhancing proteostasis, oxidative...

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a key role in responding to viral genomes and endogenous DNA byproducts by inducing inflammatory pathways. Its roles in senescence and in the response to telomere shortening have also recently been proposed. To address its role in age-related pathologies and decreased longevity associated with short telomeres, we generated double-mutant mice deficient for STING and either the telomerase RNA component (TERC)...

CONCLUSIONS: A fully automated IVR system is a valid and feasible tool for frailty screening in community-dwelling older adults. Requiring no internet or human intervention, it offers a scalable solution for population-level frailty surveillance, especially in resource-limited settings.

Scalable clinical markers of neurocognitive vulnerability in aging are needed, particularly in settings where biomarker access remains limited. Instrumental activities of daily living (IADLs) capture cognitively demanding everyday behavior and may provide a low-cost, repeatable functional marker of elevated risk. We harmonized longitudinal data from four population-based aging cohorts-CHARLS, ELSA, HRS, and SHARE-including adults aged ≥50 years with eligible baseline assessments. IADL impairment...

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative condition that is characterized by an increasing incidence rate due to global population aging, resulting in a significant social and economic burden. Current pharmacological interventions offer only limited relief and are unable to halt neuronal loss and cognitive decline. Therefore, safe and effective non-pharmacological interventions (NPIs) are needed for the management of AD. This review systematically synthesizes...

High-fidelity single-nucleotide-resolution mapping of abasic (AP) sites in mammalian genomes remains technically challenging due to low abundance and high background. Here we present DEPACE-seq (Dual-End PAB-Conjugated Endo IV-Cleaved Sequencing), a robust and easy-to-implement method for precise genome-wide profiling of AP sites. DEPACE-seq employs an N-pyrrolyl-alanine-2,2'-(ethylenedioxy)bis(ethylamine)-biotin (PAB) probe that selectively conjugates AP sites via a mild Pictet-Spengler...

In recent decades, there has been active research into how ionizing radiation at low doses, an inevitable factor in human activity, affects aging processes and which molecular genetic mechanisms underlie this influence. This study investigates the effects of mutations in PIWI subfamily genes (piwi and aub), which regulate transposable elements, on the lifespan of Drosophila melanogaster under conditions of genome instability induced by hobo transposons and chronic low-intensity irradiation (20...

Progressive aging of bone marrow hematopoietic stem cells (HSCs) underlies clonal hematopoiesis and age-associated hematologic disorders. Defining early molecular events driving HSC functional decline is essential for rejuvenation strategies. Here, we identify P-selectin (Selp) as a surface marker that stratifies HSCs into conserved functional and transcriptional states during organismal aging in humans and mice. P-selectin expression increases early during aging and remains elevated in old...

Lifestyle habits, cognitive reserve, and affective reserve (secure attachment, extraversion, psychological resilience) predict resilience in the oldest-old, though the underlying biological mechanisms remain unclear. This study explored relationships between these protective factors, 120 + NULISA CNS blood biomarkers, and multidimensional health outcomes (global cognition, mental health, walking speed) in 401 dementia-free participants (age 83-87) from the InveCe.Ab study. Using sparse partial...

CONCLUSION: These findings indicate that endurance training is associated with more favorable renal biomarker profiles in the context of chronic opioid exposure.

Robots increasingly share spaces with people, supporting delivery services and mobility for the aging populations, yet their ability to share space comfortably lacks understanding and benchmarks for designers and policy-makers. We compared human-robot (HRI) and human-human (HHI) interactions across four real-world crowd datasets spanning Europe, North America, and Asia, using a unified pipeline to detect interactions, stratify by crowd density, and model pedestrian behavior. Local motion...

Neutrophils are increasingly recognized as key orchestrators of the immunosuppressive tumor microenvironment, yet their intrinsic plasticity, short lifespan and resistance to genetic manipulation have impeded therapeutic targeting. Here, we report a non-pharmacological, biophysical immunomodulatory strategy based on cold atmospheric plasma (CAP) to reprogram tumor-associated neutrophils and restore antitumor immunity. We show that CAP simultaneously delivers reactive oxygen species and redox...

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CONCLUSIONS AND IMPLICATIONS: Community-based implementation of the WHO ICOPE pathway within routine systems is feasible and identified substantial multidomain IC impairment among otherwise independent older adults. Variation across sites highlights the need for context-specific service planning and targeted resource allocation. Embedding IC screening within community platforms, with coordinated referral pathways, supports earlier identification and management of functional decline and advances...

Dietary protein quality, not merely quantity, shapes metabolic health and aging trajectories. Fanti et al. show that moderate methionine supplementation to a low-protein, Mediterranean-inspired diet activates a GH-GLP-1-FGF21 axis that reduces adiposity and frailty without caloric restriction; their findings provide a mechanism for why traditional plant-rich diets may promote longevity while sometimes compromising physical robustness.