Aging & Longevity

Spatial transcriptomics has emerged as a transformative approach for in situ mapping of cellular heterogeneity and interactions, yet existing methods often compromise throughput, cost and tissue coverage. Here we introduce Imaging Reconstruction using Indexed Sequencing (IRISeq): an optics-free, cost-effective platform that leverages spatial interaction mapping by indexed sequencing to profile tissues at adjustable sizes and resolutions (5-50 µm). We applied IRISeq to map gene expression across...

Reducing activity of the mechanistic/mammalian target of rapamycin (mTOR) with rapamycin extends lifespan and healthspan in many species. The mechanisms by which mTOR regulates lifespan and healthspan, however, are still unknown. Understanding how mTOR signaling in different cell types regulates lifespan and aspects of healthspan is urgently needed if we are to harness the potential individual and societal benefits of healthspan extension by mTOR attenuation. mTOR kinase can form two complexes,...

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Accurate measurement of brain vascular pathology is essential for understanding its role in cognitive aging. Here we classified participants using the amyloid-tau-neurodegeneration framework in a multicenter cohort and identified cerebrospinal fluid brain endothelial-derived small extracellular vesicles (c-BEEVs) as a sensitive biomarker, which correlated with vascular risk factors and the severity of small-vessel disease. c-BEEVs showed high diagnostic performance for vascular cognitive...

Organs age at different rates, yet the protective mechanisms contributing to decelerated aging in certain tissues remain unclear. Applying cross-tissue comparisons to molecular readouts of aging, here we report that the intervertebral disc (IVD) ages slowly. We link the rate of aging to the persistently hypoxic environment of the IVD, and its unique ability to degrade hypoxia-inducible factor-1α (HIF-1α) in nucleus pulposus cells through optineurin-mediated selective autophagy, thereby...

As ageing populations worldwide confront an increasing prevalence of neurological deficits, elucidating the underlying causes and associated factors has become paramount. The decline in age-related cellular processes precipitates neurodegeneration and cognitive decline, significantly impairing quality of life. Homocysteine (Hcy), a physiological amino acid resulting from protein catabolism, can lead to hyperhomocysteinemia (HHcy) when present at elevated levels. While the deleterious effects of...

Cancer risk increases exponentially with age. As the world's population grows older, the absolute number of cancer diagnoses and cancer-related deaths continues to rise globally, despite declines in age-adjusted cancer mortality in many high-income countries. However, there is still little known about how molecular features of tumors differ according to patient age and how these genomic alterations may impact the treatment of patients of advanced age compared to younger patients who are...

Individuals, even with matched genetics and environment, show substantial phenotypic variability. This variability may be part of a bet-hedging strategy, where populations express a range of phenotypes to ensure survival in unpredictable environments. In addition, phenotypic variability between individuals ('bet-hedging'), individuals also show variability in their phenotype across time, even absent external cues. There are few evolutionary theories that explain random shifts in phenotype across...

Vitality capacity (VC) reflects a physiological state and is a determinant domain of intrinsic capacity but has so far remained mainly theoretical. This study validates the vitality capacity domains 'energy and metabolism' and 'neuromuscular function' and examines its link to locomotor capacity and quality of life (QoL). Exploratory factor analysis (EFA) was performed on the combined dataset from the Fatigue Resistance AMErsfoort study (FRAME, n = 1000) and the Fatigue Plot study (FATPLOT,n =...

Facial features undergo continuous transformations across the lifespan. This study quantified and visualized the effects of aging on facial morphology in individuals of European ancestry. Three-dimensional facial photographs of 4,038 individuals (1,455 males and 2,583 females), aged 5 to 85 years and of European descent, were analyzed. Morphological changes in the face were modeled using kernel linear regression, with a focus on age-related changes. Age- and sex-specific expected facial shapes...

Due to aging, the efficiency of kidney function begins to decrease. Dysfunction in mitochondria and their cristae is a hallmark of aging. Therefore, age-related decline in kidney function could be attributed to changes in mitochondrial ultrastructure, increased reactive oxygen species, and alterations in metabolism and lipid composition. We sought to understand how mitochondrial ultrastructure is altered over time in tubular kidney cells. A serial block face-scanning electron microscope and...

CONCLUSION: A territorial geriatric hotline integrated into local professional healthcare networks is feasible and widely utilized, as reflected by the overall call volume. It facilitates rapid access to geriatric expertise and, based on the analysis of calls with complete data, may contribute to improving patient orientation, and to proposing alternatives to emergency department transfers. However, the study design did not allow for the systematic evaluation of the clinical outcomes associated...

CONCLUSIONS: The findings indicate that if government administrators and platform developers want to implement effective SCSP development and promotion strategies, they need to pay attention to improving older adults' digital literacy, optimizing the platform's information, system, and service quality, and strengthening external publicity to enhance the platforms' social influence.

Memory decline, particularly in neurodegenerative disorders such as Alzheimer's disease, represents a critical global public health challenge, with projections exceeding 150 million cases by 2050. Current therapeutic options remain limited: while drugs like donepezil and memantine offer symptomatic relief, and newer agents like lecanemab show modest effects on slowing progression, no disease-modifying cures exist. This underscores the urgent need to refine preclinical models bridging discovery...

Modern humans now routinely survive to advanced ages, in far greater proportions than ancestral populations, and thus experience the consequences of molecular pathways optimized for youth yet still active in old age. Natural selection weakens over the course of adulthood, creating a selection 'shadow' in which deleterious late-acting mutations accumulate and alleles with early-life benefits persist despite late-life costs. An evolutionary lens helps us to understand puzzling patterns - from...

Aging has effects on the immune system that are similar in men and women, but also reshapes their immune systems in unique, sex-specific ways. These sex-specific patterns of immune aging influence disease susceptibility, vaccine effectiveness, cancer survival, and responses to pharmacological therapies, and have direct implications for preventive medicine and clinical care. However, these differences in susceptibilities and responses are rarely considered in research, clinical trials, or...

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Defective proteostasis is a hallmark of aging cells and tissues. Among the different components of the proteostasis network, in this study, we focus on a selective form of autophagy known as chaperone-mediated autophagy (CMA), and we set out to understand its physiological role in the retina. Using mice deficient for CMA [knockout for lysosome-associated membrane protein type 2A (Lamp2A)], we have found that CMA blockade leads to impaired visual function, altered retinal proteostasis, and...

Cognitive dysfunction is an increasingly recognized complication of diabetes, contributing substantially to morbidity in the aging population, yet disease-modifying therapies remain scarce. Dietary intervention, a cornerstone of diabetes management, may offer neuroprotective potential. Low-carbohydrate ketogenic diets (LCKDs), typically restricting carbohydrates to < 50 g/day, effectively improve glycemic control and metabolic health. Emerging preclinical and clinical evidence suggests that...