Research articles

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  • Liu et al. identify downregulation of DDX5, an RNA helicase, in the cartilage of patients and mouse model of osteoarthritis. Targeted upregulation of DDX5 in mouse chondrocytes inhibits hyaline cartilage fibrosis and degradation via pre-mRNA splicing and G4 unwinding, a potential therapeutic strategy against osteoarthritis.

    • Qianqian Liu
    • Mingrui Han
    • Yang Sun
    ArticleOpen Access
  • Tong et al. construct simulations using DNA methylation data to quantify what proportion of the predictive accuracy of epigenetic clocks could be explained by stochastic methylation changes, suggesting that stochasticity contributes more toward the accuracy of chronological rather than biological age predictions.

    • Huige Tong
    • Varun B. Dwaraka
    • Andrew E. Teschendorff
    AnalysisOpen Access
  • At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

    • Andrei E. Tarkhov
    • Thomas Lindstrom-Vautrin
    • Vadim N. Gladyshev
  • Meyer and Schumacher use simulations to show that accumulation of stochastic variation is sufficient to build clocks that can measure both chronological and biological age, sensitive to changes induced by smoking, calorie restriction, parabiosis and reprogramming.

    • David H. Meyer
    • Björn Schumacher
    ArticleOpen Access
  • In vivo human neuroimaging shows that locus coeruleus (LC) integrity changes precede medial temporal tau accumulation, and jointly predict future lower cognition in older people at risk for Alzheimer’s disease. A common transcriptomic profile underlies LC’s early vulnerability to tau.

    • Elisenda Bueichekú
    • Ibai Diez
    • Heidi I. L. Jacobs
    LetterOpen Access
  • Late-onset hypogonadism (LOH) can occur with male reproductive aging and is characterized by declining testosterone levels as well as other clinical symptoms. Here the authors show that dysregulated phago-/auto-lysosomes in Sertoli cells are a key feature of LOH, linking metabolism and aging, and that pharmaceutical targeting of lysosome dysfunction can alleviate LOH in mice.

    • Zhiwen Deng
    • Liangyu Zhao
    • Zhi Zhou
  • The Muscle Aging Cell Atlas presents approximately 200,000 single-cell and single-nuclei transcriptomes from 17 human donors across different ages, uncovering mechanisms of aging in muscle stem cells, myofibers and microenvironment cells, and demonstrates parallels in mouse muscle aging.

    • Veronika R. Kedlian
    • Yaning Wang
    • Hongbo Zhang
    ResourceOpen Access
  • Lipid changes across the lifespan and their role in health and longevity are incompletely understood. Here, Tsugawa and colleagues conduct untargeted lipidomics across 13 sample types and four ages in mice, considering sex and microbiome dependencies. This study provides a comprehensive resource of lipid changes with aging and highlights regulatory metabolic components, such as the enzyme UGT8, as potentially responsible for male-specific glycolipid biosynthesis in the kidney.

    • Hiroshi Tsugawa
    • Tomoaki Ishihara
    • Makoto Arita
  • Aging dynamics of complex lipids are incompletely understood. Here Janssens and colleagues describe lipids that change with age across ten tissues in mice. Notably, bis(monoacylglycerol)phosphate accumulated with age. This lipid also accumulated in muscle of older humans, and reduced upon a short bout of exercise.

    • Georges E. Janssens
    • Marte Molenaars
    • Riekelt H. Houtkooper
  • Ovarian aging has an important role in health and fertility; however, the molecular mechanisms underlying it remain incompletely understood. Here the authors use single-cell and spatial transcriptomics in reproductively young, middle-aged and older human ovarian tissue to elucidate ovarian aging. They describe spatiotemporal changes in ovarian cells and highlight the important regulatory role of FOXP1.

    • Meng Wu
    • Weicheng Tang
    • Shixuan Wang
    ArticleOpen Access
  • In a longitudinal population-based cohort, Liu et al. demonstrate that integrating polygenic risk scores and the gut microbiome improved prediction, over traditional risk factors, for heart disease, diabetes, Alzheimer disease and prostate cancer.

    • Yang Liu
    • Scott C. Ritchie
    • Michael Inouye
    AnalysisOpen Access