Aging & Longevity

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...

A coordinated response to stress is crucial for promoting the short- and long-term health of an organism. The perception of stress, frequently through the nervous system, can lead to physiological changes that are fundamental to maintaining homeostasis. Activating the response to low oxygen, or hypoxia, extends healthspan and lifespan in Caenorhabditis elegans. However, despite some positive impacts, negative effects of the hypoxic response in specific tissues prevent translation of their...

ObjectivesThis study explores the relationship between marital status, living arrangements, and aging well among Chinese adults aged 50 and older.MethodsUsing data from the China Family Panel Studies (CFPS), we developed a multidimensional measure of aging well (physiological, functional, cognitive, psychological, and subjective). Analysis was based on a five-category typology of marital and living arrangements.ResultsA clear hierarchy emerged in the findings: married individuals co-residing...

The immune-fibrotic axis functions as a vicious feedback loop where age-related chronic, low-grade systemic inflammation (inflammaging) drives maladaptive tissue repair and fibrosis, while senescent fibrotic cells in turn amplify systemic inflammation. In the aging heart, immune dysregulation and fibroblast activation drive tissue scarring and stiffening and a higher risk of heart failure and vascular disease. To identify cardiac regions and cell types affected with age, we monitored...

Rapamycin, an mTOR inhibitor, continues to be investigated for hypothesized physiological, disease prevention, and longevity benefits, but few studies have been conducted in humans. Using US national organ transplant registry data, one of the largest real-world datasets examining chronic rapamycin exposure in humans, we compared the Kaplan-Meier survival age distribution of 4885 kidney transplant recipients prescribed rapamycin compared to 6589 recipients not prescribed rapamycin. Recipients...

Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers, distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS...

CONCLUSION: Among Chinese adults aged ≥ 65 years, the cMIND diet Q2 group was significantly associated with BADL disability, while the overall cMIND diet was significantly associated with IADL disability, supporting its potential role in promoting functional independence during aging.

Dietary restriction (DR) extends lifespan in animals and plants, but its evolutionary causes are elusive. The prevailing explanation is that DR prolongs life by shifting resources from reproduction to somatic maintenance. To test this idea in Caenorhabditis elegans we developed an experimental paradigm that tricks nematodes into increasing their reproductive effort under DR via food odour cues. Although DR improved survival, experimentally increased reproduction under DR did not reduce either...

To define the role of pyroptotic macrophage-derived extracellular vesicles (EVs) in diminished ovarian reserve (DOR) and to elucidate whether EVs-mediated transfer of miR-103a-3p drives mitochondrial dysfunction in granulosa cells. Single-cell RNA sequencing data from public GEO datasets were analyzed to characterize pyroptosis-associated features in ovarian macrophages across age groups. EVs were isolated from pyroptotic macrophages and applied to granulosa cells (KGN) to assess mitochondrial...

Sirtuins are a family of enzymes that regulate cell homeostasis through pathways impacting genomic stability, mitochondrial function, cellular senescence, inflammation, and autophagy. In the skin, these pathways protect against extrinsic insults, maintain keratinocyte stem cells, and contribute to the overall structure and integrity of the skin barrier. Sirtuins decline with chronologic age, with UV exposure also impacting their activity, resulting in a loss of this homeostasis. There are 13...