Aging & Longevity

CONCLUSION: In this real-world cohort, aging appeared to influence the observable kinetics of amyloid reduction during anti-amyloid therapy. Early serial amyloid PET may provide useful information regarding longer-term amyloid dynamics, while baseline perfusion imaging may help identify patients with substantial downstream neurodegenerative burden who remain at risk for cognitive decline despite amyloid clearance. These findings highlight biological heterogeneity in treatment response and...

Transcranial magnetic stimulation (TMS), a non-invasive and non-pharmacological intervention, is increasingly being explored for mitigating age-related cognitive decline and dementia. Its therapeutic potential is largely attributed to its capacity to modulate neuronal firing rates and induce neuroplastic changes and modulate neurovascular coupling within distributed neural networks that support memory, attention, and executive function. Despite growing interest, gaps remain in understanding how...

Parkinson's disease (PD) and dementia have risen markedly in many regions. While aging, genetics, toxicants, and protein misfolding explain key aspects of pathology, they do not fully account for synchronized temporal trends or pronounced regional heterogeneity in recent increases. This hypothesis and theory article proposes that persistent microorganisms in industrial food systems-particularly biofilm-forming spirochetes in high-throughput poultry processing-may represent an under-recognized...

ObjectivesThis study examined whether social engagement mediates the relationship between information and communication technology (ICT) use and depression and anxiety among older Americans.MethodsData came from 5,195 respondents in the 2022 National Health and Aging Trends Study. Multivariate mediation analyses were conducted using bootstrapping and Monte Carlo simulation to estimate indirect effects.ResultsCompared with non-users, ICT users showed greater social engagement and lower depression...

The effect of NAD^(+) in enhancing mitochondrial function and energy metabolism in human cells is closely linked to NAD^(+)-dependent sirtuins (i.e. SIRT1 and SIRT3). SIRT2 primarily functions in the cytoplasm, where it can serve as a key deacetylase for tubulin and modulates stability of microtubules. Microtubule plays a pivotal role in regulating mitochondrial dynamics, including mitochondrial movement, fission/fusion, repair, and mitophagy-dependent clearance. However, the potential role of...

A crucial factor limiting the physiological relevance, reproducibility and ease of adoption of microphysiological systems is the constrained non-specific design and performance of existing perfusion systems. Inspired by the physics of the accordion music instrument, we have engineered Hemadyne, a standalone mechanical pump with compact footprint that operates without any additional instruments. The pump is paired with a custom-built control algorithm to reproduce clinical waveforms with a...

Aging leads to renal function decline and increases the risk of chronic kidney disease (CKD). Omega-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids for humans, exerting their functions via free fatty acid receptor 4 (FFAR4). Clinical studies indicate that omega-3 PUFAs supplementation shows benefits for the elderly population and CKD patients, but these results remain controversial. Herein, we found that omega-3 PUFAs alleviated renal fibrosis and tubular senescence in aged mice,...

Artificial intelligence (AI) methods, including machine learning (ML), are transforming healthcare by enabling personalized interventions that integrate multimodal data to support rehabilitation, preventive care, and remote monitoring. Despite their broad potential, older adults remain underrepresented in model development, raising concerns about bias and limited generalizability. As AI/ML adoption expands, it is essential to critically appraise emerging tools to ensure ethical, equitable,...

Human longevity is a complex trait shaped by genetic background and population-specific factors. Calabria, a region in Southern Italy with a high prevalence of centenarians and relative genetic isolation, is a valuable model for investigating the genetic architecture of extreme survival. Here, we performed a genome-wide association study of longevity in 705 Calabrian individuals, comparing long-lived subjects to younger controls using a mixed-model approach that accounts for relatedness and...

CONCLUSIONS: Purposeful digital engagement can improve orientation and alleviate loneliness in Chinese older adults. It also helps preserve orientation ability partly by reducing feelings of loneliness, whereas use proficiency may exacerbate loneliness and diminish life satisfaction.

Despite the landmark identification of twelve hallmarks of aging (López-Otín et al., 2023), geroscience lacks a formal account of why these hallmarks interact and amplify each other, why mono-target interventions show systematically limited efficacy, and what determines the threshold at which compensatory mechanisms fail. A recent extension of the hallmarks framework has further integrated psychosocial and social determinants of aging (López-Otín & Kroemer, 2025; Kroemer et al., 2025),...

Undercarboxylated osteocalcin (ucOCN), a bone-derived hormone, modulates neurocognition and emotional regulation. Its concentration declines with aging but rises secondarily in females with estrogen deficiency caused by ovarian decline. Using an ovariectomized (OVX) mouse model, we found serum ucOCN sharply increased in early OVX stages with normal behavioral performance, whereas prolonged estrogen loss decreased ucOCN and induced cognitive and emotional impairments. Ocn knockout mice failed to...

Aging is a well-recognized risk factor in cardiovascular diseases (CVDs), primarily due to its association with the gradual decline in cardiac function. This decline significantly influences the pathogenesis of common CVDs such as myocardial infarction and heart failure. Despite the existence of several proteomic atlases of the heart, the spatially resolved proteomic dynamics essential for understanding region-specific aging mechanisms in cardiac tissue remain incompletely characterized. In this...

Adult hippocampal neurogenesis declines with age, but the stress pathways that shape neural precursor cell (NPC) survival and lineage progression remain incompletely understood. Here, we tested whether ferroptosis-related vulnerability contributes to the regulation of hippocampal NPCs and their progeny. Using in vitro assays, transcriptomic analyses, and in vivo genetic and pharmacologic perturbations, we find that NPCs show features consistent with elevated susceptibility to ferroptotic stress...

Somatic stem cells are characterized by their low overall protein-synthesis rates, a feature implicated in driving their stemness. However, how aging reshapes the translational landscape of stem cells remains poorly understood. Here, we present an in vivo single-cell ribosome profiling strategy to monitor tissue-wide translational landscapes of the epidermis during aging. By implementing ribosomal elongation-inhibited cell isolation and switching to RNase I, we expand the applicability of...

Nutritional support for healthy aging is an active field of research. Bovine organ extracts, and glandular therapy in general, became popular in the 1900s, but their effect on healthy aging is unexplored, and their mechanisms of action are unclear. Here, we evaluated three bovine thymus materials with regards to their effect on healthy aging in C. elegans: two thymus extracts, a nuclear fraction (TNF) and a cytosolic fraction, and desiccated bovine thymus. All three materials extended C. elegans...

The aim of this study was to evaluate the effects of prolonged exposure to hypertriglyceridemia induced by overexpression of the human apolipoprotein CIII (apoCIII) gene, as well as the impact of age, on the liver of genetically modified mice. A total of 32 male mice, aged 5 and 20 months, were divided into transgenic (CIII) and non-transgenic (NTG) groups. Biochemical analyses of blood and morphological assessments of liver and adipose tissue were performed. ApoCIII overexpression resulted in...

Circulating proteins provide insights into an individual's health and aging trajectory. However, little is known about their long-term temporal stability. We evaluated the five-year temporal stability of 7288 serum proteins in 3093 participants (mean age 75 years) of the AGES-Reykjavik study. We observe wide variability in protein temporal stability, independent of transcriptomic stability in tissues. Temporally stable proteins tend to be extracellular, secreted, and tissue-specific, while...

Human immune responses vary across individuals due to both genetic and environmental factors. We previously established the Milieu Intérieur cohort to define boundaries of healthy immune variation and identify their determinants. To evaluate how immune responses change over time and test whether immune states can predict future disease, we conducted a 10-year follow-up of the cohort. Here we show widespread changes in humoral responses to pathogens over this period, including unexpected...

Carbon membranes yielding high selectivity as well as high permeance are attractive to advance the membrane-based gas separation. Herein, we report ultrathin carbon membranes (UCMs) which deliver enhanced gas separation performance through oxygen-modulated pyrolysis of poly(4-vinylpyridine) precursor. We show that O(2) in pyrolysis environment, transforms the otherwise uniform carbon network featuring a ~ 3.9 Å characteristic interlayer spacing into disrupted UCMs (d-UCMs). These d-UCMs possess...