Aging & Longevity

CONCLUSIONS: A higher cognitive reserve is linked to a decreased risk of developing frailty, slower progression, and a greater likelihood of improvement from pre-frailty to non-frailty, suggesting that lifelong cognitive enrichment enhances the physiological reserve beyond cognition. These findings suggest that interventions and policies that support the development of cognitive reserve across the life course may contribute to healthier frailty trajectories in later life.

CONCLUSIONS: Sleep quality and frailty are associated with CMM, suggesting that their combined assessment may enhance predictive accuracy for CMM risk. These findings underscore the need to prioritize high-risk elderly individuals for integrated interventions addressing sleep disturbances and frailty, thereby facilitating the transition from reactive to proactive cardiometabolic care models.

Bone marrow aging compromises hematopoiesis and immunity, yet whether these processes are modifiable in primates remains unexplored. Here, we map the single-cell transcriptomic landscape of primate bone marrow aging and demonstrate that long-term oral vitamin C (VC) supplementation attenuates selected molecular and progenitor-level decline. Aging drives severe common lymphoid progenitor (CLP) depletion, myeloid-biased hematopoietic stem and progenitor cell (HSPC) output, and anatomical...

Skeletal aging involves pyrophosphate/phosphate disequilibrium and impaired mechanotransduction, which together constrain osteogenic repair. We develop OsteoVes, a matrix-vesicle-mimetic extracellular organelle that combines tissue-nonspecific alkaline phosphatase (ALP)-mediated inorganic pyrophosphate (PPi) hydrolysis, nano-hydroxyapatite nucleation, and a mesenchymal stem cell-derived membrane interface for extracellular matrix anchoring. In aged human mesenchymal stem/stromal cells (MSCs),...

Clonal haematopoiesis of indeterminate potential (CHIP) represents somatic mutations in haematopoietic stem cells that drive clonal expansion. Epigenetic age acceleration (EAA), estimated from DNA methylation (DNAm) clocks, may capture age-related changes in haematopoiesis. This systematic review and meta-analysis was conducted to synthesise evidence on associations between CHIP and EAA and explore shared biological mechanisms that may underlie this relationship. Six databases were searched from...

The Eatwell Guide represents the UK's principal healthy eating model and understanding whether adherence to UK dietary recommendations can attenuate age-related functional decline is essential to inform healthy ageing strategies. In up to 157,457 participants from the UK Biobank, we explored cross-sectional and prospective associations between adherence to the Eatwell Guide and markers of physical function (grip strength, fat-free mass percentage, self-reported walking pace, and falls). Eatwell...

Proteostasis collapse, a hallmark of aging and neurodegeneration like Alzheimer's disease (AD), causes irreversible damage in late life. Whether late-life proteostasis capacity is developmentally programmed remains unclear, as mechanistic studies requiring lifelong tracking and molecular manipulation are challenging or impossible in long-lived species. Using C. elegans as a lifelong, genetically tractable AD model, we uncover a critical early-life window during which reducing TIP60/NuA4...

Trained immunity is a state of heightened immune response that is initiated in hematopoietic stem cells (HSCs) and mediated mainly by their myeloid progeny. Aging-associated inflammation drives many aging-related diseases, yet its biological origin is largely unknown. Here we show that SIRT3, a mitochondrial deacetylase highly expressed in HSCs but reduced during aging, suppresses the HSC response to aging that drives maladaptive trained immunity, chronic inflammation and tissue functional...

Health problems associated with aging have become increasingly severe in recent years. For example, hepatic lipid metabolism declines as the body ages, leading to lipid metabolic disorders. Although exosomes have been explored for treating metabolic diseases, there is currently a paucity of research regarding aging-related changes in hepatic lipid metabolism. Herein, we cultured human umbilical cord mesenchymal stem cells (HucMSCs), from which we extracted HucMSC-derived exosomes (HucMDEs). We...

Medical genetic studies focus on high-risk groups to enrich for targeted phenotypes. Although genetic effects may vary across the lifespan, age-related enrichment of target phenotypes can also arise from cumulative environmental exposures, without requiring changes in genetic architecture. Accumulating environmental effects over the lifetime can inflate nongenetic variance, creating the illusion of greater genetic signal while in fact masking underlying genetic effects. We propose investigating...

Commercializing perovskite solar cells (PSCs) will likely require the scalable deposition of homogeneous perovskite films under ambient conditions. However, the spatially heterogeneous degradation of metastable perovskites during prolonged coating leads to nonuniformity. Here, we demonstrate spatiotemporally homogeneous crystallization of α-phase FAPbI(3) (where FA is formamidinium) enabled by a phase-locking strategy that establishes a dynamically evolving, moisture-buffering intergranular...

Aging disrupts tissue homeostasis across organ systems. Here, we identify tissue-resident macrophages (TRMs) as central coordinators of age-related organ decline through impaired clearance of senescent neutrophils, a process regulated by the immunomodulatory prostaglandin E2 (PGE(2)) receptor EP2. Reducing TRM EP2 signaling in aged mice preserved youthful mitochondrial fitness and prevented cognitive decline, frailty, sarcopenia, adiposity, cardiac impairment, and systemic inflammation. Plasma...

A prostaglandin prevents macrophages from clearing toxic neutrophils in aging organs.

CONCLUSIONS: Choose Home was highly acceptable to Veterans and caregivers, who perceived improvements in health, self-management, and caregiving self-efficacy. By filling a gap between acute and longitudinal services, Choose Home may strengthen efforts to deliver whole-person, home-based care. Continued implementation and rigorous evaluation are warranted to assess long-term outcomes and scalability within VA and beyond.

Aging involves a gradual loss of cellular balance, leading to reduced function and increased disease risk. While impaired proteostasis is a key hallmark of aging, more evidence shows the importance of RNA homeostasis (ribostasis), particularly the regulation of circular RNAs (circRNAs). CircRNAs are stable RNA molecules that build up over time and are linked to age-related cellular dysfunctions. In this regard, Kim et al. 2026 provide new insights into the impact of circRNA turnover on aging and...

Regulatory T cells (Tregs) are essential for maintaining immune tolerance. We recently identified chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, as a critical regulator of Treg function. Treg activation induces CMA, but this response is markedly diminished with aging. Mice lacking CMA specifically in Tregs develop systemic inflammation, impaired immune tolerance and reduced lifespan. We confirm that CMA is a fundamental mechanism supporting Treg suppressive...

Hypertension affects one-third of adults and is a major comorbidity of neurocognitive disorders. The causal relationship, shared genetic architecture, and upstream mechanisms linking hypertension to brain aging remain unclear. Hypertension GWAS datasets from MVP and FinnGen R12 were meta-analyzed as the exposure, and a European-ancestry brain age gap (BAG) GWAS derived from the UK Biobank and LIFE-Adult cohorts was used as the outcome. MR and GSMR assessed causality. LDSC, HDL, and S-LDSC...

The main goal of the present study was to examine the effects of a high-velocity resistance training (HVRT) program on the force-velocity (F-V) profile of different groups of aging adults. An additional aim was to explore whether individual baseline F-V profiles were associated with training-induced improvements in muscle power and functional capacity. Middle-aged and older adults with and without mobility limitations (n = 36, 61 ± 13 years) completed a 12-week HVRT program (2 days/week, 40-60%...

Veterans are vulnerable to housing instability and/or homelessness (HUH) and may encounter unique challenges that affect their healthcare. While research has noted connections between major psychiatric disorders and HUH, few studies have examined personality disorders (PD) and their sex-specific relationships with HUH and healthcare use among aging veterans. We examined sex differences in the epidemiology of PD and their impact on healthcare service use among aging HUH veterans. A...

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