Aging & Longevity

CONCLUSIONS AND IMPLICATIONS: Among community-dwelling older adults, MRI-derived muscle quality deteriorated substantially faster than muscle quantity over 4 years and more closely paralleled declines in physical performance. These findings suggest that age-related muscle deterioration is driven primarily by qualitative degeneration rather than simple loss of muscle mass and support the use of imaging-based muscle quality measures as sensitive biomarkers of biological muscle aging.

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CONCLUSION: HBDL-based free-weight resistance training is a safe, feasible, and effective strategy to improve body composition, trunk extensor function, and mobility in older women.

Homotypic targeting is the inherent ability of cells to preferentially interact with cells of the same type, a phenomenon seen in cell adhesion, tissue formation and immune responses. However, its potential remains underexploited. Here we report a strategy to substantially enhance homotypic targeting through extracellular vesicles secreted by cells. By engineering the surface of small extracellular vesicles (sEVs) with lanthanides, we amplify specific cell-sEV interactions by more than 25-fold,...

Sickle cell disease (SCD) is a blood disorder affecting millions worldwide. Emerging evidence reveals that SCD pathophysiology increases the risk of myeloid malignancies and hematopoietic stem cell (HSC) dysfunction, likely because of chronic stress on bone marrow. To investigate this further, we interrogated bone marrow hematopoietic stem and progenitor cells (HSPCs) from mice and individuals with SCD and observed molecular signatures of chronic cellular stress including oxidative stress, DNA...

Balance and lower limb muscle strength are essential factors in preventing falls in older adults. This randomized controlled trial investigated the effect of 8 weeks of dynamic neuromuscular stability (DNS) exercises on static balance, dynamic balance, and lower limb strength in older men. Thirty older men aged 61-76 years were randomly allocated to either a DNS exercise group (n = 15) or a control group (n = 15). The experimental group performed DNS exercises for 8 weeks (3 sessions/week),...

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are now recognized as integral components of the proteostasis network that preserves cellular and tissue function across the lifespan. With aging, increasing oxidative load, metabolic imbalance, and Ca²⁺ dysregulation elevate the burden of misfolded proteins in the ER, leading to progressive UPR engagement. When ER stress is mild or transient, UPR signaling restores folding capacity, restrains translation,...

17α-estradiol (17α-E2) extends median lifespan and improves metabolic homeostasis in male mice through estrogen receptor α (ERα)-dependent mechanisms, but female mice are largely unresponsive unless ovariectomized or subjected to chronic high-fat feeding. Whether the gradual hormonal transition of natural reproductive aging similarly unmasks female responsiveness to 17α-E2 remains unknown. We tested whether 4-vinylcyclohexene diepoxide (VCD)-induced depletion of the ovarian reserve would render...

Aging is characterized by a progressive decline in cellular and tissue function, shaped in part by disruptions in communication between the extracellular matrix (ECM) and intracellular signaling networks. The cell surface receptor CD44 functions as a molecular hub, integrating signals from a remodeled ECM to regulate core aging programs including senescence, inflammation, and metabolic balance. This review synthesizes evidence that CD44, through its structural domains, isoform diversity, and...

DNA methylation is an established biomarker of human ageing and is used by a variety of tools to identify meaningful epigenetic signals. We investigated whether analysing CpGs grouped by transcript as functional units could generate a ranked list of transcripts most correlated with age that might otherwise be overlooked in genome-wide CpG-based studies. Here we present Epitage ( https://github.com/a00s/epitage ), a continuously updated ranked list of transcripts built from the GSE87571 dataset...

CONCLUSIONS AND IMPLICATIONS: The LSA did not show evidence of predictive validity for adverse outcomes among middle-aged and older Canadian adults after a 3-year follow-up. This may be because of the CLSA sample being relatively highly functioning at baseline, the 3-year-long gap in assessment, and the low prevalence of adverse outcomes in this sample. Further research is needed to determine the usefulness of the LSA for predicting these adverse outcomes at the population level.

CONCLUSIONS AND IMPLICATIONS: Machine learning models demonstrated substantial predictive performance with interdisciplinary team-determined follow-up interval categories among community-dwelling older adults. Explainable artificial intelligence analyses highlighted the contribution of multidimensional geriatric assessment domains to individualized follow-up planning. These findings support the potential role of artificial intelligence-assisted decision support in home-care scheduling, although...

Meningeal (dural) lymphatics are essential for cerebrospinal fluid (CSF) clearance to cervical lymph nodes, yet the precise pathway is incompletely understood. Using a multifaceted approach in mice, we examined tracer dynamics and the CSF outflow pathway from the subarachnoid space (SAS) to the nasal mucosa and identified a discrete arachnoid region surrounding the olfactory bulbs with abundant fenestrations. Similar arachnoid fenestrations were found in cynomolgus monkeys. Fluorescent tracers...

Senescent cells in the aging and diseased brain are increasingly recognized as highly heterogeneous catalysts of dysfunction, originating from diverse cell types and characterized by wide-ranging molecular signatures and functional outcomes. Additionally, technological advances in single-cell transcriptomics and mouse modeling have helped reframe senescence from a static fate to a dynamic trajectory that is heavily influenced by evolving environmental cues. In this review, we identify key hubs...

Changes in the gut microbiota occur throughout the human lifespan, and maintaining microbial homeostasis plays a critical role in promoting healthy aging. In recent years, substantial progress has been made in elucidating the mechanistic links between aging and microbiota remodeling, highlighting the central role of microbiota-host interactions in regulating immune responses and maintaining metabolic homeostasis. These findings provide new potential targets for the precision prevention and...

Chronic inflammation increases with age and contributes to cancer progression and therapeutic resistance, yet the mechanisms underlying this process remain incompletely understood. Here, we identify an increased frequency of pro-inflammatory myeloid cells in aged mice and humans, characterized by elevated production of IL-1α, IL-1β, IL-6, and TNF-α. These cells are enriched in the breast tumor microenvironment and are associated with accelerated tumor progression. Using heterochronic parabiosis...

Early-life nutrition is linked to adult brain health, yet evidence from quasi-experimental studies remains scarce. Leveraging the UK's historical sugar rationing as a natural experiment, we examined whether early-life sugar restriction reduces the risk of neurodegenerative and psychiatric disorders in later life. Among 60,394 UK Biobank participants (born 1951-1956), three groups were defined: in-utero-only, in utero plus 2 years, and non-rationed controls. Compared with non-rationed...

The gut virome is emerging as a key contributor to host physiology, yet it remains underexplored relative to the gut bacteriome. Despite comprehensive viral catalogs for the human gut, comparable resources for mice, the principal model organism in biomedical research, remain lacking, limiting our understanding of virome-host interactions and their implications for host health and disease. Here, we present Mouse Reference Gut Virome (MRGV), a comprehensive catalog comprising 109,778 viral genomes...

Senescence, the endpoint of normal cells' replicative lifespan, is accompanied by a complex sequence of molecular events. One such event is the dramatic reorganization of CTCF into senescence-induced clusters (SICCs). However, the molecular determinants, genomic consequences and functional purpose of SICCs remain unknown. Here we combine three-dimensional genomics, super-resolution imaging, DNA tracing and functional assays with modeling to dissect SICC emergence. We find that, on senescence...

Understanding the links between metabolism, ageing, and age-related phenotypes may clarify the role of ageing in disease onset and improve risk prediction. We conducted a cross-cohort assessment of biological age using broad-spectrum LC-MS metabolomics of 3,686 plasma samples in 2,295 participants, aged 20-89, from the UK Airwave study (N = 960) and the Irish Longitudinal Study of Ageing (N = 1,335). The nucleoside N(2),N(2)-dimethylguanosine, C-glycosyltryptophan, bile acid glucuronides, and...