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The liver plays a central role in regulating systemic metabolism, and its function declines with age, contributing to increased susceptibility to metabolic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by hepatic lipid accumulation and inflammation, is an early manifestation of liver dysfunction strongly associated with aging, insulin resistance, and high-fat diet (HFD) consumption. Ames Dwarf mice, which are growth hormone (GH)-deficient and...

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Epigenetic drift is a key feature of aging and is associated with age-related diseases including cancer, yet the underlying molecular mechanisms remain unclear. Here, by analyzing DNA methylation and gene expression data from healthy and cancerous human colon samples, we identify an aging and colon cancer-associated DNA methylation (DNAm) drift. We find evidence that this drift is conserved in the mouse intestinal epithelium, where we demonstrate its origin within intestinal stem cells and...

Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (n = 43,616) and validated their high accuracy in cohorts from China (n = 3,977) and the USA (n = 800; cross-cohort r = 0.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly...

Intraneuronal aggregates of the microtubule-associated protein tau play a pivotal role in Alzheimer's disease and several other neurodegenerative syndromes. Anti-tau antibodies can reduce pathology in mouse models of neurodegeneration and are currently being tested in humans. Here, we performed a large-scale seroepidemiological search for anti-tau IgG autoantibodies (ατ) on 40,497 human plasma samples. High-titer ατ+ individuals were surprisingly prevalent, with hospital patients being three...

Recent advances in ultra-accurate sequencing technologies have revealed that somatic mutations accumulate throughout the human lifespan and may contribute to both normal aging and disease. These mutations are highly diverse, often non-recurrent, and functionally heterogeneous, making their biological impact difficult to evaluate systematically. Although many studies have profiled somatic mutations in individual tissues or limited cohorts, a centralized and scalable platform that integrates...

Lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, is characterized by aggressive growth, immune resistance, and high tumor heterogeneity. Here, we demonstrate that genetic loss of protein kinase Cι (PKCι), which is found in ∼20% of LUAD patients, alters the trajectory of mouse Kras/Trp53-driven LUAD tumors from one resembling lung development to one mimicking lung regeneration. As a result, a major subset of tumor cells with PKCι loss exhibit cellular senescence and...

The telomerase RNA-protein enzyme is critical for most eukaryotes to complete genome copying by extending chromosome ends, thus solving the end-replication problem and postponing senescence. Despite the importance of the fission yeast Schizosaccharomyces pombe to biomedical research, very little is known about the structure of its 1212 nt telomerase RNA. We have determined the secondary structure of this large RNA, TER1, based on phylogenetics and bioinformatic modeling, as well as genetic and...

Synapses must be resilient to the challenges they confront during development, experience, disease, and aging. A conserved form of adaptive plasticity, observed at the glutamatergic Drosophila neuromuscular junction (NMJ), is expressed following acute pharmacological blockade of postsynaptic glutamate receptors (GluRs). This challenge is counteracted by enhanced presynaptic neurotransmitter release to maintain stable synaptic strength. This retrograde form of homeostatic plasticity is termed...

The abnormal protein degradation implicated in the pathogenesis of Parkinson's disease was previously attributed to defective H+ leakage from lysosomes via TMEM175 (https://doi.org/10.1016/j.cell.2022.05.021). In this issue, Riederer et al. (https://doi.org/10.1083/jcb.202501145) demonstrate that TMEM175 is instead a K+ channel, minimally permeable to H+.

DNA recovered from people buried at the site reveals surprises

Identity of the toe bones and other fossils could shake up the human family tree

CONCLUSION: Osteosarcopenia and its components (osteoporosis and sarcopenia) are inversely associated with BMI and fat mass, particularly in the trunk and android regions.

BackgroundWhile life expectancy has increased globally, chronic disease burdens remain high. Cancer, despite improved survival, remains a major cause of disability and the second leading cause of death. Though behavioral risks such as smoking, poor diet, and physical inactivity are linked to cancer, few studies examine their impact on cancer-free life expectancy and gender disparities.MethodsUsing U.S. Health and Retirement Study data (2004-2020) and a multistate model approach, we estimated...

CONCLUSIONS: To effectively assess autonomy in older adults, the focus must be on life goals and insights from caregivers. Our future tool may address this gap in clinical practice by capturing these essential aspects, ultimately enhancing quality of life in older adults.

CONCLUSION: Frailty, malnutrition, cognitive impairment, and depressive symptoms were frequent among community-dwelling very old adults, particularly women. These cross-sectional findings emphasize the need for multidisciplinary and gender-sensitive strategies within HACs to support functional independence and mental well-being. Longitudinal and multivariate studies are warranted to confirm these associations.

BACKGROUND: The Department of Veterans Affairs (VA) is the largest integrated healthcare system in the United States and serves a rapidly aging patient population. The VA's Home-Based Primary Care (HBPC) program is a home care model for older, complex, high-risk Veterans that provides comprehensive, longitudinal primary care delivered by an interdisciplinary team of VA staff, with plans for expansion by 2027. HBPC program implementation varies considerably across local sites and contexts....

CONCLUSION: This study shows a significant association between spousal health and cognitive function among older adults, with frailty serving as a fully mediator in this association. Crucially, activity engagement is associated with a weaker impact of frailty on cognitive abilities, with greater involvement linked to less pronounced cognitive decline. These findings emphasize the dual protective roles of a spouse's health and activity engagement in sustaining cognitive health.

CONCLUSIONS: The literature on vision screening in this population was sparse and there was heterogeneity in current practices, highlighting the need for standardised screening protocols. More research is needed to evaluate vision screening services in this population and to explore implementation barriers.

CONCLUSIONS: This study presents a decade-spanning model that reflects the multifactorial nature of fall risk and the diversity of aging trajectories in the U.S., providing a foundation for more inclusive and personalized fall prevention strategies.