Aging & Longevity

Genome-wide association studies strongly implicate neuroinflammation in late-onset Alzheimer's disease (LOAD). Genetic risk loci for LOAD are enriched for genes expressed in microglia, but the relationship among microglial LOAD risk genes has been unclear. We found that the N-terminal SH2 domain of INPP5D, an important LOAD risk gene, directly interacted with the cell death regulator RIPK1 at p-Y383 to suppress RIPK1 kinase activation. Microglial INPP5D deficiency cell-autonomously promoted...

In aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to cognitive decline in neurological diseases, they remain largely unstudied in the context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes in the aged hippocampus, with substantial variation among 32 inbred BXD mouse strains. Genetic mapping through quantitative trait locus analysis identified a major locus...

The analysis of spatial transcriptomics is hindered by high noise levels and missing gene measurements, challenges that are further compounded by the higher cost of spatial data compared to traditional single-cell data. To overcome this challenge, we introduce spRefine, a deep learning framework that leverages genomic language models to jointly denoise and impute spatial transcriptomic data. Our results demonstrate that spRefine yields more robust cell- and spot-level representations after...

No abstract

A fundamental question in biology is whether all cells age. Embryonic stem cells (ESCs) defy the norm as rare normal cells capable of indefinite in vitro passage. However, the mechanisms underlying ESC lineage immortality remain unresolved. Using long-term live-cell imaging to follow the fates of single ESCs, we show that ESC lineage renewal is achieved through sporadic entry into a state characterized by the expression of two-cell embryo-specific markers. During this state, cells undergo...

The nuclear envelope (NE) is essential for cellular homeostasis, yet its integrity declines with age, accelerating functional deterioration. Here we report a mitochondria-to-NE signalling pathway that safeguards NE integrity through redox-dependent lipid metabolism. In Caenorhabditis elegans, reducing mitochondrial ETC activity preserves NE morphology during ageing. This effect requires developmental mitochondrial superoxide, which downregulates SBP-1 (SREBP orthologue) and suppresses...

No abstract

Different neuron types show distinct susceptibility to age-dependent degeneration, yet the underlying mechanisms are poorly understood. Here we applied aging clocks to single neuron types in Caenorhabditis elegans and found that distinct neurons differ in their biological age. Ciliated sensory neurons with high neuropeptide and protein biosynthesis gene expression show accelerated aging and degeneration, correlating with loss of function, which could be prevented by pharmacological inhibition of...

Platinum-based chemotherapy is commonly used for non-small cell lung cancer (NSCLC) and high-grade serous ovarian cancer (HGSOC) treatments, yet clinical outcomes remain poor. Cellular senescence and its associated secretory phenotype (SASP) can have multiple tumor-promoting activities, but both are largely unexplored in these cancers. In this study, using xenograft, orthotopic and Kras^(G12V)-driven murine NSCLC models, we demonstrate that cisplatin-induced senescence strongly promotes...

CONCLUSIONS: Our findings indicate that both mold exposure and analgesic use are associated with an increased likelihood of arthritis in older adults, underscoring the need to improve damp and deteriorating housing conditions and to promote the rational use of analgesics to support healthy aging.

CONCLUSIONS: Our results uncover sex-specific, nonlinear aging programs that capture the dynamics of epigenetic change beyond linear models. These findings provide potential candidate biomarkers for early disease risk and advance understanding of how aging trajectories diverge between sexes.

Understanding oocyte and ovarian aging has become critically important, as trends in family planning evolve, with many women choosing to have children later in life. The ovary, a crucial organ in female reproduction, is particularly susceptible to age-related changes and is one of the organs that exhibit functional deterioration most distinctly with age. The aging of female reproductive systems also affects longevity and various health outcomes. A better understanding of both oocyte and ovarian...

Polluting cooking fuels are a major source of household air pollution and may reduce life satisfaction (LS). Yet, this relationship remains unexplored in India where polluting fuel use is still widespread. We utilized cross-sectional data from the Longitudinal Aging Study in India, a nationally representative study of individuals aged 45 years and above. Cooking fuel type was classified as households using clean fuels (CF) or non-CF. Based on kitchen type, non-CF was categorized into non-CF in...

CONCLUSION: This explorative study suggests that the individual perceptions of GS may impact the use of medical services. Future confirmatory studies are necessary to develop targeted interventions addressing these perceptions in order to improve the health behavior of older adults.

No abstract

No abstract

CONCLUSION: Greater adherence to the cMIND dietary pattern is independently associated with lower probability of LMM and better physical performance among older Chinese adults. These findings suggest potential benefits of promoting MIND diet principles for maintaining musculoskeletal health in aging populations.

Age-associated dysbiosis, marked by shifts in the composition of gut microbiota and gut microbiota-derived metabolites (GMDMs), is increasingly implicated in driving systemic low-grade inflammation during aging. The disrupted GMDM pools, including altered levels of short-chain fatty acids (SCFAs), secondary bile acids (BAs) and tryptophan (Trp) metabolites, lead to mucosal barrier dysfunction, immunometabolic dysregulation, and modulation of innate and adaptive immune cells. In turn, this...

Neuropathic pain (NP) creates a severe pathological condition that primarily affects elderly people because of their accumulated neurobiological changes that make them more susceptible to persistent pain. The aging process leads to multiple mechanisms that combine neurodegeneration with immunosenescence and mitochondrial dysfunction with impaired autophagy and glial priming, and ion channel dysregulation to create a nociceptive environment. This review examines how mitochondrial breakdown and...

While human lifespan has increased dramatically over the past century, the extension of healthspan, the period free of chronic age-related disease, has lagged behind. Blood flow and angiogenesis are significantly reduced in aging humans, playing a crucial role in mediating cardiovascular disease and heart failure - major causes of reduced lifespan. However, these mechanisms have not been studied as extensively as cellular and molecular mechanisms in animal models. Healthful aging, due to...