Aging & Longevity

Cerebrovascular and neurodegenerative diseases rank among the leading causes of death worldwide and represent an increasing socioeconomic burden, particularly in aging populations. Pluripotent stem cell (PSC)-based therapies have emerged as promising strategies for replacing lost neurons and restoring neural circuits in disorders of the central nervous system (CNS). However, major barriers remain, including poor survival, limited integration, and variable functional maturation of transplanted...

In the mammalian host, Trypanosoma brucei proliferates as slender bloodstream forms before undergoing quorum-sensing (QS)-dependent differentiation into non-dividing transmissible stumpy-QS forms, a process that both controls parasitaemia and enables transmission to the tsetse fly. However, this model does not explain how transmission occurs in chronically infected patients and cattle, where parasite densities are often too low to trigger QS-mediated differentiation. We identify a relevant...

Sepsis triggers profound organism-wide disturbances, yet the cellular logic underlying its systemic impact remains poorly defined. By integrating single-cell transcriptomes from six septic tissues, we uncovered a conserved cross-tissue program characterized by inflammation-driven senescence, disrupted intercellular communication, and coordinated transcriptional reprogramming. Senescence signatures were broadly elevated across cell types and strongly coupled to altered communication networks,...

Regulation of insulin secretion by pancreatic β-cells is central to maintaining glucose homeostasis and overall metabolic health. Glucose is recognized as the major driver of insulin secretion; however, here, we highlight established and emerging evidence of important contributions of other nutrients, including amino acids, fatty acids and alternative fuels, as well as non-nutrient factors, in modulating both basal and postprandial insulin release. We discuss molecular mechanisms underlying...

CONCLUSION: Given the critical role of spiritual health, targeted strategies to promote PIL are needed to enhance healthy aging. The findings highlight PIL as the strongest predictor of capability well-being, alongside subjective health and financial factors within the Thai cultural context.

CONCLUSIONS: The life satisfaction rate of older adults in Hubei Province of China was relatively high, which was associated with both demographic factors and consumption-related factors. Consumption reflecting active social participation was positively associated with life satisfaction, while consumption reflecting obligatory or stressful activities was negatively associated. The study provided preliminary empirical evidence that may inform the development of aging policies and services.

Senescent cells accumulate following chemotherapy and during aging, where they contribute to dysfunction through the pro-inflammatory arm of the senescence-associated secretory phenotype (SASP), termed NF-κB-associated SASP (NASP). Here we show that short-term inhibition of CDK4/6 with abemaciclib suppresses established NASP in pre-existing senescent cells both in vitro and in vivo. This senomorphic effect reduces the pro-tumorigenic activity of chemotherapy-induced senescent cells and improves...

The RNA-binding protein Sex-lethal (Sxl) is classically known as a master regulator of sex determination and mRNA splicing in Drosophila melanogaster. However, this role is not conserved across species, and functions beyond the canonical pathway remain poorly understood. In this study, we uncover a splicing-independent role for Sxl at the chromatin level in the Drosophila brain. Using Targeted DamID (TaDa) profiling in neurons, we identify widespread binding of Sxl to promoter regions,...

Astrocytes play essential roles in neuropathology. Human astrocytes exhibit unique properties, highlighting the importance of studying astrocytic responses in human models. Varicose projection astrocytes, previously considered exclusive to hominoids and a physiological type of astrocytes, were suggested to reflect pathological burden, albeit direct evidence linking them to neurological diseases has been lacking. Here, we demonstrate that varicose projection astrocytes also appear in other...

CONCLUSION: Among the included studies, featuring a minimal outsole, a textured insole design, and a high collar design showed consistency to benefit older adults that provides textured feedback while offering foot protection, which may enhance balance control. However, some studies also implied that certain designs may have potential negative effects, including toe-beveled, minimal outsole, less-fixation, and barefoot condition. The lack of comprehensive descriptions of experimental footwear...

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...