Aging & Longevity

Ageing is a complex process influenced by modifiable factors such as diet, which may accelerate or decelerate physiological decline. While chronological age increases uniformly, biological ageing varies between individuals, reflecting differences in health status and the resilience of biological systems. The Klemera-Doubal Method (KDM), a composite biomarker-based index often used as an estimate of biological age, has been associated with morbidity and mortality in large cohorts. This study...

This study examined the extent to which processing speed moderates the relationship between age and crystallized intelligence and influences the indirect effect of age on verbal working memory in 233 healthy middle and older adults aged 51-94 years. Participants were screened for cognitive impairment and depressive symptoms before completing a battery of cognitive tests. Data were analyzed using moderated mediation models with bootstrapping. Correlational analyses revealed significant negative...

Pink1 (PTEN-induced kinase 1) is a key guardian of mitochondrial quality via mitophagy; its mutations are tightly linked to early-onset PD. This review synthesizes how aging, exercise, and high-fat diet (HFD) modulate Pink1 activity and thereby PD risk. Aging down-regulates Pink1, impairing clearance of damaged mitochondria and promoting α-synuclein aggregation. Exercise up-regulates Pink1-Parkin signaling, enhances PGC-1α and brain-derived neurotrophic factor (BDNF), and protects dopaminergic...

BACKGROUND: Chronic kidney disease (CKD) and cognitive frailty frequently co-occur in older adults, compounding adverse health outcomes and placing substantial strain on healthcare systems.

INTRODUCTION: Aplysia californica has been a useful model system for studies of the neural basis of behavior, learning, and aging. While the latter topic has been explored with respect to several of its simple reflex behaviors, this study represents the first examination of how one of Aplysia's more complex behaviors, escape locomotion, is affected in animals nearing the end of their natural lifespan.

INTRODUCTION: Sleep disruption and metabolic decline are key contributors to cognitive aging and dementia risk. While cerebral glucose utilization declines with age, ketone metabolism remains relatively preserved, suggesting that ketogenic interventions may enhance brain energetics, sleep quality, and cognition in older individuals. Therefore, we investigated the effects of a ketogenic diet (KD) and β-hydroxybutyrate ester (KE) supplementation on sleep-wake architecture and novel spatial memory...

Humans have evolved adaptive mechanisms that enable survival even with zero calories for periods of months or longer. Intermittent 'low-dose' exposure to the metabolic stress of fasting may also activate pathways that promote metabolic health and longevity, although such benefits have not been proven in humans. Here we present our perspective of the current rationale and evidence base to support fasting for gain in metabolic health. In the absence of individual level risk factors for potential...

Several studies suggest that higher skeletal muscle mass (SMM) may be associated with a lower risk of adverse cardiometabolic outcomes. However, the relationship between SMM and cardiometabolic multimorbidity (CMM) has not been evaluated. We investigated the prospective association between height-indexed SMM and CMM risk in an older population. Data were analyzed from 3348 participants (mean age 64 years; 45.1% men) in the English Longitudinal Study of Ageing who were free of hypertension,...

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Impaired immune responses are a key feature of aging; however, there are few laboratory tests that link these responses to clinical outcomes. Interferon-gamma release assays (IGRAs) for tuberculosis screening quantify release of interferon-gamma by T-cells, and the difference between unstimulated and mitogen-stimulated T-cells is assessed for test validity. We assess this measure's relationship with all-cause mortality. We obtained the most recent negative and indeterminate outpatient IGRAs from...

High-affinity, allergen-specific immunoglobulin E (IgE) responses play a central role in allergic disease, yet the biological basis of their persistence remains incompletely understood. Studies examining IgE ontogeny have yielded diverse and often conflicting results regarding the longevity of IgE-expressing B cells, their developmental relationship to IgG1^(+) intermediates, and their dependence on germinal center (GC) reactions. In this review, we summarize the current knowledge of the...

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Gain-of-function screening in Drosophila melanogaster provides a powerful approach for identifying genes that modulate lifespan; however, induction strength and environmental stress can substantially influence phenotypic outcomes. Here, we performed a pilot Gene Search (GS)-based overexpression screen using a heat-inducible hs-GAL4 driver and compared lifespan analyses at 25 °C and 30 °C to evaluate the impact of induction conditions on the detectability of lifespan-modulating genes. Induction...

Machine learning can unravel heterogeneous patterns of brain aging and neurodegeneration, but existing methods offer limited insights into disease progression due to reliance on cross-sectional data. We introduce Coupled Cross-sectional and Longitudinal Non-negative Matrix Factorization (CCL-NMF) to capture dominant brain aging patterns by simultaneously leveraging cross-sectional and longitudinal neuroimaging data. CCL-NMF allows individuals to co-express multiple patterns, capturing mixed...

CONCLUSIONS: About four in five older Brazilians meeting dementia criteria had no prior clinical diagnosis, with marked sociodemographic and regional disparities. Both individual factors-such as age, education, and multimorbidity-and structural inequities across regions influenced diagnostic likelihood. Strengthening early-detection strategies, improved health professional training, and regionally tailored approaches may improve recognition of dementia in Brazil's public health system.

The existence and functional significance of immature neurons in the adult human brain, particularly in the context of neurodegenerative disorders, remain an open question. Although rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus both under healthy conditions and in Alzheimer's disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing in aged...

Recent studies report that epithelial differentiated cells can undergo a reverse process called dedifferentiation in response to stem cell loss. However, the extent of this reversion and the plasticity of young versus aged-differentiated cells remain unclear. Here we show that dedifferentiated corneal epithelial cells acquire a transcriptomic state closely resembling native stem cells, sustain tissue homeostasis across lifespan and efficiently repair repeated tissue injury. Transplantation of...

Cellular senescence plays a significant role in age-related conditions like osteoarthritis (OA) and intervertebral disc degeneration, in part due to the accumulation of senescent cells (SCs) in musculoskeletal tissues. Identifying novel therapeutics that can clear SCs is crucial for improving musculoskeletal health in the elderly. The present study aimed to elucidate the changes in Class I histone deacetylases (HDACs) and their role during senescence. All Class I HDACs except HDAC1 were...

Aging is commonly viewed as a passive consequence of accumulated damage; however, emerging evidence suggests that it may also represent an adaptive response to environmental stress. Here, we combined transcriptomic and metabolomic profiling of Saccharomyces cerevisiae to investigate how short-term, long-term, and recovery phases of stress exposure shape cellular physiology and lifespan. Short-term stress-induced protective pathways and longevity-associated metabolites, including trehalose and...

While exercise is shown to reduce hippocampal atrophy, the underlying molecular mechanisms remain to be fully elucidated. Animal studies suggest the myokine irisin underlies exercise-related hippocampal benefits, though human evidence is lacking. We cross-sectionally examined 74 healthy older adults (age 65.47 ± 8.56 years). Participants completed Godin Leisure-Time exercise questionnaires, provided fasting blood for irisin measurement and underwent structural MRI with hippocampal subfield...