Aging & Longevity

CONCLUSION: The combination of low PEF and high cardiometabolic burden identified an older subgroup at elevated risk of incident ADL disability. However, the small and heterogeneous multiplicative interaction and near-null additive interaction estimates did not support a consistent interaction beyond the separate associations.

CONCLUSIONS: This multi-database explainable machine learning analysis reveals robust cross-sectional predictive associations between frailty and concurrent depression among older adults with multimorbidity. The predictive models facilitate clinical risk stratification for the concurrent screening of high-risk individuals for both conditions. However, the present cross-sectional design prohibits confirmation of temporal ordering and causal reciprocal reinforcement. The findings highlight the...

CONCLUSIONS: Physical performance assessed by the SPPB was significantly associated with dementia risk. These findings support the potential value of the SPPB in identifying older adults at higher risk of dementia. Future intervention studies are needed to determine whether improving physical performance can reduce dementia risk.

CONCLUSION: L1 expression increased in the aged mouse PFC and is associated with coordinated downregulation of neuronal gene networks rather than other major aging-associated transcriptional programs. These findings further characterize the molecular context of increased L1 expression during normal brain aging.

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Aging is the dominant risk factor for retinal neurodegeneration, yet the upstream regulators that coordinate senescence-associated programs across retinal cell types remain incompletely defined. Here we combined bulk RNA-seq and quantitative proteomics of retinas from naturally aged (24-month) and young (4-month) mice to define age-associated molecular programs and infer upstream regulators. We identified coordinated but imperfect transcript-protein coupling, with prominent immune and metabolic...

A progressive decline in testosterone levels is a hallmark of male reproductive aging and is closely associated with impaired Leydig cell function. Leydig cell function relies on intracellular homeostasis, with endoplasmic reticulum (ER) homeostasis playing a particularly important role in steroidogenesis. The ER supports steroidogenesis by regulating protein quality control, lipid and cholesterol metabolism, calcium homeostasis, and interactions between organelles. With advancing age, the...

How diet shapes aging and age-related diseases marked by senescent cell accumulation remains unclear. Here we report vanadyl sulfate (VS), a mineral dietary supplement, as a senolytic agent. Oral VS ameliorates phenotypes of aging and diverse age-related disorders and extends lifespan in male mice. Integrated functional omics analyses show that senescent cells exhibit globally reduced proteome cysteine reactivity but increased expression and apparent cysteine reactivity of proteins essential for...

Torque teno viruses (TTVs) are ubiquitous components of the human virome whose replication is tightly regulated by host immunity. While elevated total TTV load has been associated with increased mortality in older adults, the clinical relevance of species-level virome composition remains unclear. We profiled the circulating anellovirome in 251 hospitalized older adults using amplicon-based whole-genome sequencing and investigated associations with frailty, cognitive impairment, mortality, immune...

Multiple object tracking (MOT) is a core function of dynamic visual attention that relies on the ability to simultaneously monitor several moving objects. Although MOT performance is known to decline with age, and to depend on efficient oculomotor strategies, how these processes interact across the adult lifespan and under degraded visual input remains poorly understood. Here, we examined age-related differences in MOT under normal and gaze-contingent viewing conditions simulating central and...

We characterize the spatiotemporal dynamics of the tumor microenvironment (TME) in bladder cancer (BLCA) samples before and after neoadjuvant immunotherapy in a multicenter real-world cohort (n = 606). We identify two distinct differentiation outcomes in BLCA epithelial cells: sensitivity and resistance to immunotherapy. Additionally, we identify SERPINH1 as a common target of acquired immunotherapy resistance in BLCA. Furthermore, we characterize an immunotherapy-induced tumor-myeloid barrier,...

T cell senescence is an important dysfunctional state associated with tumor progression, but whether senescent T (Tsen) cells directly reprogram tumor cell behavior remains unknown. Here, single-cell transcriptomic analyses identify abundant Tsen cells across breast, colorectal, and lung cancers. Tsen cells actively promote tumor growth, metastasis, stemness, and chemotherapy resistance by reprogramming tumor cells in vitro and in vivo. Mechanistically, lipid-enriched senescence-associated...

Sarcopenia is characterized by progressive loss of skeletal muscle strength, mass, and function during aging, driven by impaired proteostasis, mitochondrial dysfunction, altered metabolism, regenerative failure, and neuromuscular decline. Experimental models are needed to determine how these processes drive muscle degeneration and identify testable therapeutic mechanisms. Zebrafish combine whole-animal physiology with genetic manipulation, live imaging, and scalable phenotypic analysis, making...

Osteoporosis is a highly prevalent age-related disorder, and accumulating evidence suggests that it does not arise in isolation but is intrinsically linked to the aging process. Here, we employed integrative methods to systematically identify the relationship between aging and osteoporosis, and uncover the critical cell types and molecular regulators that mediate this association. Observational analysis of phenotypic data from UK Biobank and Mendelian Randomization analysis of summary-level...

Aging is accompanied by alterations in inflammatory signaling, regulated cell-death pathways, and cellular stress responses in the brain. This study investigated the effects of propolis and dexpanthenol, administered individually or in combination, on gasdermin-related, inflammatory, and heat-shock gene expression in naturally aged male mice. Thirty-five male CD-1 mice were randomly allocated to five groups (n = 7/group): Young Control, Aged Control, Aged + Propolis, Aged + Dexpanthenol, and...

Cellular senescence and its associated secretory phenotype (SASP) represent a fundamental mechanism of biological aging. SASP-related inflammation has been implicated in cardiovascular disease. However, its role in perioperative risk in cardiac surgery remains largely unexplored, and established risk scores such as EuroSCORE II and the STS Score do not regard biological aging or senescence. In this prospective single-center cohort study, 131 patients aged ≥ 65 years undergoing elective cardiac...

Biological aging is complex and resists any single mechanistic narrative. This article develops a conceptual framework for aging biology through a series of brief statements on central topics in the field, with the goal of discussing aging simply, directly and accessibly. The organizing principle is that aging is a default outcome of living: because biological processes are inherently imperfect, deleterious changes (the deleteriome) accumulate over time and progressively erode functional...

Nicotinamide Adenine Dinucleotide (NAD) is a critical cellular coenzyme whose decline associates with various chronic and inflammatory diseases. Improved NAD restoration may reduce disease risks and extend healthy lifespan. We report here that certain commensal bacteria including specific probiotic species produce (amide-)N-methylnicotinamide (N-MNA), which is a structural isomer of methylnicotinamide, a nicotinamide degradative metabolite. Patients with gut dysbiosis and inflammation show...

Aging is a major risk factor for melanoma. However, it is unclear whether aging fuels tumor evolution by altering mutation rates, changing the microenvironmentally induced selection on drivers, or both. We analyzed 5472 melanomas, estimating how selection on individual variants changes with patient age while accounting for differing neutral mutation rates. Neutral mutation rates increased only modestly with age; ultraviolet damage remained predominant, but endogenous processes increasingly...

mTORC1 activity is increased in muscle with aging and is implicated as a potential driver of age-related declines in muscle health. While pharmacological inhibition of mTORC1 improves lifespan and healthspan, it remains unclear whether chronic activation of mTORC1 is sufficient to accelerate aging in skeletal muscle. We aimed to address this question using an inducible model of muscle-specific knockout of Depdc5, which encodes the protein DEP domain containing 5 (DEPDC5), a negative regulator of...