Aging & Longevity

The "healthy drinking" paradox refers to situations where alcohol consumption is misleadingly associated with better health outcomes, a pattern frequently observed in observational studies that are prone to a range of confounding factors. Some recent studies developing organ-specific proteomic aging clocks report that alcohol consumption is linked to slower aging in select organs, even as it accelerates aging in others, thus echoing this paradox, with substantial discrepancies across such...

Cardiovascular health, depressive symptoms, and cognitive performance are closely interconnected and jointly influence all-cause mortality. We investigated the independent associations of Life's Simple 7 (LS7), depressive symptom trajectories, and cognitive performance with all-cause mortality and conducted exploratory four-way decomposition analyses to evaluate complementary mechanistic hypotheses linking these factors. We analyzed data from the Healthy Aging in Neighborhoods of Diversity...

Perovskite photovoltaics are limited by structural instabilities initiated during crystallization and amplified under operation. We report that a lattice-matched Prussian blue scaffold directs heterogeneous nucleation to produce highly oriented, strain-relaxed films. Its redox-active Fe-C≡N-Fe network mediates the conversion of Pb⁰ and I⁰ defects, and its rigid open framework suppresses A-site cation redistribution and the resulting electronic inhomogeneity under bias. This strategy yielded...

Infant macaques showed immune changes and signs of faster aging years after inhaling smoke.

Fibrotic remodeling of tissues and tumors establishes immunosuppressive microenvironments that drive organ dysfunction and, in cancer, limit response to immunotherapy. Senescent-like cells are conserved drivers of fibrosis and therapeutic targets, yet their functional heterogeneity complicates therapeutic intervention. Here, we show that P-selectin is expressed by a subset of senescent-like cells in fibrotic tissues and tumors. Leveraging fucoidan-based nanoparticles that bind P-selectin, we...

Targeting senescence decreases fibrosis and boosts the response of cancer cells to immunotherapy.

Although cortical thinning and atrophy are well documented in aging and neurodegenerative disease, the cortical structural features associated with preserved or superior cognition across typical adulthood remain incompletely characterized. We examined associations between cortical thickness and cognitive performance in a large, typically aging cohort and tested whether they vary by age and cognitive domain. We analyzed cross-sectional data from cognitively healthy adults in the Human Connectome...

CONCLUSIONS: A machine learning-derived CFI integrating diagnoses, medications, and procedures demonstrated robust prediction of mortality and other adverse outcomes, supporting its incremental value in population-based frailty assessment.

Wearable devices offer the ability to objectively characterize free-living physical activity; however, raw step-count data generated by commercial devices require systematic processing before they can support rigorous inference. We describe a transparent, reproducible standard operating procedure (SOP) for transforming epoch-level step-count data from commercial Garmin devices into participant-level analytic variables and demonstrate its application in the STRRIDE-PD Reunion study: a long-term...

CONCLUSION: Midlife MetS was associated with modest reductions in within-network DMN connectivity, with abdominal obesity and low HDL cholesterol as the primary contributing MetS components. Reduced DMN connectivity was associated with poorer verbal fluency performance. These findings suggest that subtle differences in higher-order functional brain network organization associated with metabolic syndrome can be detected during midlife and are related to cognitive functioning, highlighting the...

β-Nicotinamide mononucleotide (NMN), as the precursor of nicotinamide adenine dinucleotide (NAD^(+)), has remarkable therapeutic potential in aging-associated diseases. Skeletal muscle exhibits not only reduced mass but also impaired strength and function during aging. However, the protective effects of NMN against skeletal muscle cell senescence remain to be fully elucidated. In this study, we used D-galactose (D-gal) to establish a senescence model in C2C12 cells. Our results demonstrate that...

Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that mediate intercellular communication by transferring proteins, nucleic acids, and lipids. Within the hematopoietic system, EVs orchestrate critical signaling between bone marrow (BM) niche cells and hematopoietic stem and progenitor cells (HSPCs) to regulate quiescence, proliferation, and lineage commitment. During aging, senescence and telomere attrition drive a profound remodeling of EV biogenesis and cargo. Aged EVs,...

CONCLUSIONS: Although AgeTech standardization is advancing, critical gaps remain. Limited attention to safety, security, privacy, and digital economy and community inclusion raises concerns for trust, equity, and sustainable adoption. Addressing these gaps through targeted and coordinated standardization efforts is essential to support inclusive, trustworthy, and scalable AgeTech solutions in the context of rapid global population aging.

Nearly a century ago, restricting diet during early-life periods was suggested to extend lifespan in rats and in Daphnia^(1,2). The effect of juvenile diet on adult physiology and lifespan has subsequently been described in other model organisms, including fruit flies^(3-5) and mice^(6-8); however, its mechanism remains poorly understood. Here, using Drosophila as a model, we show that restricting protein intake during the larval stage (early-life protein restriction; ePR) promotes adult...

Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes that are crucial for physiological homeostasis and ageing¹. mTORC1 preferentially regulates the translation of 5'-terminal oligopyrimidine (TOP) motif-containing mRNAs (which encode mainly ribosomal proteins) through the 4E-BP translational repressor²; however, this function of mTORC1 is resistant to rapamycin inhibition³. TOP mRNAs are exceptionally abundant, and thus impose a...

Centuries ago, Thomas Sydenham famously wrote, "A man is as old as his arteries", highlighting the importance of the vasculature for health and healthy aging. Here, we review recent developments in vascular aging research, focusing on how microvascular aging drives tissue dysfunction and the emerging therapeutic opportunities for vascular rejuvenation. Although macrovascular aging has long been studied, microvascular aging remains an emerging frontier. Recent single-cell and multiomic...

Changes in cell type composition play an important role in human health and disease. Recent advances in single-cell technology have enabled the measurement of cell type composition at increasing cell lineage resolution across large cohorts of individuals. Yet this raises new challenges for statistical analysis of these compositional data to identify changes in cell type frequency. We introduce crumblr ( DiseaseNeurogenomics.github.io/crumblr ), a scalable statistical method for analyzing count...

Disrupted rest-activity rhythms have been associated with aging and chronic disease, yet longitudinal evidence from free-living populations has been lacking. Here we integrate multi-year Fitbit activity data from the All of Us Research Program with clinical biomarker-derived PhenoAge from 2,222 participants (8,447 person-years). Through high-dimensional digital phenotyping, we show that circadian rest-activity rhythm intensity, timing, and stability are associated with biological aging...

The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease^(1,2). Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal ageing and its relationship to psychiatric and neurodegenerative disorders. The dorsolateral prefrontal cortex has a central role in higher cognitive functions and is particularly sensitive to age-related decline³,...

Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited^(1,2). Here, to gain deeper insights into the aetiology of different brain diseases, we used specimens from 1,494 unique donors to generate a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, comprising over 6.3 million individual...