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  • Inhibitors of sodium glucose co-transporter 2 (SGLT2) have long been used in the treatment of diabetes and cardiovascular disease, owing to their modulation of glucose levels. Katsuumi and colleagues now show that, in addition to their glycemic effects, SGLT2 inhibitors modulate senescence immune surveillance by downregulating PD-L1 expression on senescent cells.

    • Guangran Guo
    • Corina Amor
    News & Views
  • A study in Nature Aging on electronic health records from 1.7 million people in New Zealand reveals that most patients with dementia have a history of hospital-treated infection. In a dementia-free population, individuals with a severe infection were at a threefold-higher risk of dementia even 25 years later.

    • Mika Kivimäki
    • Keenan A. Walker
    News & Views
  • Aging-related DNA methylation changes are numerous. Their precise measurement has opened new avenues to explore aging-related disease pathology, including the construction of chronological and biological age predictors (termed DNA methylation ‘clocks’). Three studies investigate the substantial stochastic contribution to these epigenetic changes and further our understanding of aging biology, as well as of these predictors.

    • Christopher G. Bell
    News & Views
  • Zou and colleagues design and analyze a health education program that targeted college students (who were grandchildren) to encourage older persons who had already had their first COVID-19 vaccine dose to receive a booster. The program increased the uptake of booster doses, which highlights the fact that family ties can have positive roles in the context of a pandemic.

    • Bruno Arpino
    News & Views
  • Zhou and colleagues explore reversing testicular aging and late-onset hypogonadism by targeting lysosomal function in Sertoli cells. The aging-related transformation of Sertoli cells into a lipid-hoarding subtype with dysregulated phagolysosomes and autolysosomes was reversed using the TRPML channel agonist ML-SA1, which demonstrates the potential of this targeted therapy in alleviating testosterone decline and systemic male-aging phenotypes.

    • Ariane Zamoner
    • Pedro Fontes Oliveira
    • Marco G. Alves
    News & Views
  • Xu and colleagues used partial OSKM reprogramming in aged mice to drive cell-type proportions of the subventricular zone to more youthful levels, which equates to qualified rejuvenation of a neurogenic niche that is defined, in part, by restoration of neuroblast levels.

    • Niels C. Asmussen
    • Marissa J. Schafer
    News & Views
  • Epidemiological studies reveal a correlation between hearing loss and the development and progression of Alzheimer’s disease (AD), but the underlying causal mechanisms remain unclear. A study now provides experimental evidence that hearing loss can promote AD via the growth differentiation factor 1 (GDF1) pathway, which may aid in developing potential AD therapeutic strategies.

    • Hong-Bo Zhao
    • Yang Yang
    News & Views
  • The extracellular matrix is an essential component of the tumor microenvironment and affects cancer progression. Weeraratna and colleagues have now uncovered that age-related reductions in the level of hyaluronan and proteoglycan link protein 1 (HAPLN1) stimulate neoangiogenesis and compromise the vascular integrity of intratumoral blood vessels. These biological modifications converge to fuel distant melanoma metastasis.

    • Corine Bertolotto
    News & Views
  • Suda and colleagues explore the enduring consequences of plasma membrane injury in budding yeast and mammalian cells. Their findings highlight that membrane damage induces irreversible cell-cycle arrest and premature cellular senescence, whereas upregulation of plasma membrane repair suppresses them.

    • Stine Lauritzen Sønder
    • Jesper Nylandsted
    News & Views
  • Amor and colleagues previously developed chimeric antigen receptor (CAR) T cells that can target and eliminate senescent cells. The utility of these senolytic CAR T cells is now expanded to show that they can combat age-related metabolic dysfunction, and that they can be used prophylactically and have effects that persist for months, thus opening the door to the development of long-term senolytic approaches.

    • Jenna M. Bartley
    • Ming Xu
    News & Views
  • Ying et al. integrate Mendelian randomization into epigenetic clock making and pioneer a strategy to develop aging biomarkers with stronger causal ties to healthspan. They distinguish signs of aging-related molecular damage from responses to it that might signal resilience.

    • C. P. Ryan
    • D. W. Belsky
    News & Views
  • Oleson et al. tackle the enduring question of the extent to which transient events during development shape our outcomes by studying the effects of early-life exposure to oxidative stress. They find that a cascade of changes initiated by the epigenetic-modifier COMPASS complex manifests in rearrangements in lipid metabolism in adulthood, which confers broad protection against amyloid-induced proteotoxicity.

    • Supriya Srinivasan
    News & Views
  • Two recent studies discover a scaling law of mammalian lifespans: the speed at which DNA methylation drifts from a youthful state strongly associates with maximum lifespan.

    • Francesco Morandini
    • Andrei Seluanov
    • Vera Gorbunova
    News & Views
  • Targeting tau in addition to amyloid-β could be the next phase of disease modification in Alzheimer’s disease. The TANGO trial of gosuranemab, which binds the tau N terminus, affected neither clinical outcomes nor brain levels of aggregated tau. The results highlight the importance and challenge of reducing aggregated tau.

    • Andrew M. Stern
    • Reisa A. Sperling
    News & Views
  • Epigenome deregulation is considered a hallmark of aging; however, the function of the alteration of DNA methylation in aged tissues is a long-standing question. Hong and colleagues reveal the mechanism and consequences of DNA methylation loss at heterochromatin regions in aged hematopoietic stem cells.

    • Anna Krepelova
    • Francesco Neri
    News & Views
  • Female fecundity decreases one to two decades before the menopausal transition. A study by Zhang et al. now identifies aging-related decline of the polyamine spermidine as a crucial bottleneck for oocyte quality. Supplementation with spermidine rejuvenates oocytes in vitro and in vivo, and leads to improved fertility of middle-aged female mice.

    • Andreas Zimmermann
    • Frank Madeo
    News & Views
  • Human aging is associated with increased rates of many cardiac diseases and tissue remodeling. However, disentangling the mechanisms that underlie normal heart aging from disease processes is challenging. A study now addresses this gap by investigating healthy primate cardiac aging and provides evidence that SIRT2 signaling may regulate cardioprotective effects.

    • Laura Cox
    • Michael Olivier
    News & Views
  • A recent publication in Nature Aging suggests that DOPA decarboxylase may serve as an emerging biomarker that can identify neurodegenerative disorders that are characterized by dopaminergic cell loss. Here we discuss how this finding can assist clinicians and researchers in the differential diagnosis of individuals who present with parkinsonism or cognitive decline.

    • Marcel M. Verbeek
    • Bastiaan R. Bloem
    News & Views
  • Intestinal barrier dysfunction is a hallmark of aging. Zhang and colleagues examine the replenishment of adherens junctions in the intestine of aged Caenorhabditis elegans and discover the role of the SDPN-1–RAB-10 axis in the dysregulated endocytic recycling, offering new insights into the age-dependent impairment of the intestinal barrier.

    • Yifan Chen
    • Yidong Shen
    News & Views
  • Lysosomes are small vesicles in which cellular constituents are enzymatically degraded. Villalobos and colleagues now show that in Caenorhabditis elegans a shift in lysosome morphology from a vesicular to a tubular shape is critical for the lifespan extension triggered by calorie restriction. Moreover, tubular lysosomes form even in well-fed descendants of calorically restricted parents for up to four generations.

    • Tímea Sigmond
    • Tibor Vellai
    News & Views