Aging & Longevity

In senescent cells, functional alterations in organelles like mitochondria and lysosomes are well characterized, but senescence-associated changes in Golgi function are not. An RNA interference screen revealed that silencing subunits of the coatomer protein I (COPI) complex, critical for intracellular transport involving the Golgi, reduced extracellular vesicle uptake. In proliferating WI-38 fibroblasts, silencing COPI constituents COPA, COPB1, COPB2, or COPD induced ATF4 production and...

Changes in gene expression have been observed in the aging human brain, but our understanding of the underlying regulatory mechanisms remains limited. To unravel these complexities, we analyzed single-nucleus gene expression, chromatin accessibility, DNA methylation, and three-dimensional (3D) chromatin architecture from human hippocampal tissues spanning the adult lifespan. We identified both linear and nonlinear dynamic gene regulatory programs during aging. Between the ages of 50 to 75,...

Aging tissues gradually lose cellular diversity due to stem cell exhaustion. A new PLOS Biology study utilizes advanced lineage tracing to track intestinal stem cell lineages across the life span. The findings reveal clonal attrition happens in early ages.

CONCLUSION: Older adults with intact tactile sensation showed stronger hand dexterity-cognitive associations, highlighting sensorimotor integrity as relevant for early screening and functional evaluation. Stratified patterns suggest possible cognitive group differences that merit further study.

Cellular senescence is a context-dependent cellular state characterised by persistent cell-cycle arrest, epigenetic remodelling, metabolic reprogramming and acquisition of a senescence-associated secretory phenotype. Transient senescence contributes to embryogenesis, tissue repair and tumour suppression, whereas persistent senescent cell populations accumulate with advancing age across multiple tissues, in part owing to declining immune-mediated clearance and intrinsic resistance to apoptosis,...

Global population ageing is increasing the burden of chronic disease, functional decline, and loss of independence. For most organs, decline in function starts during the 5th decade of life. Micronutrient (MN) insufficiencies/deficiencies are common and may accelerate biological ageing. MNs are required to support multiple physiologic processes, including mitochondrial homeostasis. Age-related declines in organ function are tightly linked to mitochondrial dysfunction, oxidative stress,...

Heterochronic parabiosis improves physiological and cognitive function in aging rodents; these benefits appear to be derived from the removal of aged blood plasma components and the addition of younger ones. In humans, removing plasma from older individuals with Alzheimer's disease (AD) and replacing it with saline and albumin delayed cognitive deterioration in a large clinical trial. However, mimicking heterochronic parabiosis in humans by removing large volumes of a patient's blood plasma and...

CONCLUSIONS: AGE-PAIRS demonstrates the feasibility of engaging physician alumni as mentors in early geriatrics education and suggests that structured intergenerational mentorship can support empathy and professional identity formation. Future work will integrate AGE-PAIRS more deeply into graded coursework, add structured mentor reflections, expand participation across all class years, and evaluate higher-level outcomes such as geriatrics knowledge, clinical performance, and interest in...

INTRODUCTION: Fidelity of detailed information retrieved from long-term memory (LTM) declines in aging due to changes affecting learning and remembering processes. Such behavioral deficits correspond with functional alterations in the hippocampal formation. However, it is unclear whether age-related decline in high-fidelity retrieval alters functional connections between hippocampal and cortical regions.

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.