Aging & Longevity

Immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have been targeted in cancer therapy, however, the efficacy of these interventions remains limited. Beyond its immune function on T cell surfaces, CTLA-4 is also expressed in various intrinsic cancer cells, where it influences cell proliferation, metastasis, and apoptosis. The present study aimed to investigate the function of CTLA-4 in...

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Frailty, a hallmark of systemic vulnerability in aging populations, is increasingly recognized in the clinical management of chronic respiratory diseases (CRDs). Molecular mechanism underpinning the relationships remain insufficiently elucidated. This study hence aimed to investigate whether proteomic biomarkers-circulating plasma proteins reflecting systemic inflammation, metabolism, and tissue remodeling-are associated with CRDs and may serve as potential mediators of the observed links. We...

Our ability to sense the position and movement of our limbs is essential for all activities of daily living. This ability arises from the signal sent by muscle spindles to the brain. While there is clear evidence for age-related changes in the quantity of muscle spindles and in their sensitivity, behavioral assessment of age-related changes in position sense have produced mixed findings even though it is taken as textbook knowledge that proprioception declines with age. Yet, study results are...

CONCLUSION: Among community-dwelling older adults, the composite IC score demonstrated a significant independent association with an elevated risk of hip fracture. Regular monitoring of individual IC scores may serve as an early warning indicator to initiate preventive interventions.

In their recent study, Zhang et al. (Aging Clin Exp Res, 2025) report an association between a composite unhealthy lifestyle score and the risk of comorbid type 2 diabetes mellitus (T2DM) and arthritis in the CHARLS cohort. While the topic is of significant public health relevance, we have identified several substantive methodological and interpretative limitations that temper the conclusions. Chief among these are the oversimplified and unvalidated definition of lifestyle exposures,...

CONCLUSIONS: Hospitalization due to COVID-19 was associated with poorer multidimensional aging outcomes, whereas vaccination appeared protective against functional decline. These findings highlight the importance of preventive strategies and sustained vaccination coverage to preserve functionality and promote healthy aging in post-pandemic populations.

CONCLUSIONS: Specific muscle synergy patterns are associated with balance recovery and stability maintenance. Fractionation and merging of muscle synergies triggered in response to perturbations may relate to functional decline in older adults, serving as a mechanism for remodeling to adapt to changes in limb biomechanics and multiple motor task commands.

Dimensionality reduction is routinely applied to single-cell transcriptomic data to improve interpretability, remove noise and redundancy, and enable visualization. Most existing methods aim at preserving the most prominent data properties, which can lead to omission of rare but important signals. Here we propose a novel framework, SAKURA, that uses knowledge-derived genes of interest to guide dimensionality reduction, which can help cluster rare cells and separate highly similar cell...

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The global rise in life expectancy is accompanied by an increase in the prevalence of mental health conditions among older adults, including mild cognitive impairment (MCI), dementia, delirium, depression, anxiety, and other severe mental illness. These conditions significantly impact independence, increase healthcare costs, and increase mortality risk. Mounting evidence underscores the central role of modifiable lifestyle factors-particularly physical activity and diet-in the prevention and...

CONCLUSIONS: Changes in loneliness were associated with an increased risk of subsequent CMM in both China and South Korea, with the strongest associations observed among individuals experiencing persistent loneliness. These findings indicate that loneliness is a dynamic and potentially modifiable risk factor for cardiometabolic multimorbidity across different sociocultural contexts. Early identification and targeted interventions addressing loneliness may contribute to the prevention of CMM...

Although mechanistic studies support a beneficial effect of several dietary flavonoids on telomere length (TL), to our knowledge no studies have examined associations between habitual flavonoid intakes and TL in population-based studies. We examined the associations between habitual intake of major flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols and their polymers, and anthocyanins) and TL in a cross-sectional analysis of 4,944 disease-free females from the Nurses' Health...

CONCLUSION: Our findings demonstrated the positive association between CF and TIC, highlighting the need for appropriate and timely management of CF and personalised interventions for this vulnerable group to delay premature institutionalisation.

ObjectivesOlder U.S. military veterans with cardiovascular disease (CVD) are at elevated risk for functional decline. This study examined sociodemographic, health, and psychosocial correlates of overall and domain-specific functioning in this population.MethodsData were drawn from 757 veterans aged ≥60 years with CVD who participated in the National Health and Resilience in Veterans Study. Bivariate, multivariable, and relative importance analyses were used to identify key correlates of...

Genome-wide association studies strongly implicate neuroinflammation in late-onset Alzheimer's disease (LOAD). Genetic risk loci for LOAD are enriched for genes expressed in microglia, but the relationship among microglial LOAD risk genes has been unclear. We found that the N-terminal SH2 domain of INPP5D, an important LOAD risk gene, directly interacted with the cell death regulator RIPK1 at p-Y383 to suppress RIPK1 kinase activation. Microglial INPP5D deficiency cell-autonomously promoted...

In aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to cognitive decline in neurological diseases, they remain largely unstudied in the context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes in the aged hippocampus, with substantial variation among 32 inbred BXD mouse strains. Genetic mapping through quantitative trait locus analysis identified a major locus...

The analysis of spatial transcriptomics is hindered by high noise levels and missing gene measurements, challenges that are further compounded by the higher cost of spatial data compared to traditional single-cell data. To overcome this challenge, we introduce spRefine, a deep learning framework that leverages genomic language models to jointly denoise and impute spatial transcriptomic data. Our results demonstrate that spRefine yields more robust cell- and spot-level representations after...

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A fundamental question in biology is whether all cells age. Embryonic stem cells (ESCs) defy the norm as rare normal cells capable of indefinite in vitro passage. However, the mechanisms underlying ESC lineage immortality remain unresolved. Using long-term live-cell imaging to follow the fates of single ESCs, we show that ESC lineage renewal is achieved through sporadic entry into a state characterized by the expression of two-cell embryo-specific markers. During this state, cells undergo...