Geroprotective interventions for healthy aging

Rejuvenation and partial reprogramming are two frontier areas in the field of aging. Here, the authors summarize advances in these fields and suggest future directions for research and therapy.

Technical challenges have previously hindered the detailed study of in vivo senescent cells. Here, the authors deeply characterize senescent skeletal cells across murine aging, establishing CD24 as a marker of osteolineage cells cleared by senolytics.

Cellular senescence is involved in many disease processes but few senolytic compounds are currently known. Here, the authors report the discovery of three senolytics using machine learning models trained solely on published data, with large reductions in drug screening costs.

Muscle stem cells drive muscle regeneration and are affected in myotonic dystrophy type 1. Here, the authors demonstrate that some muscle stem cells show signs of senescence in myotonic dystrophy type 1 and administer senolytics to eliminate these defective cells and restore myogenesis.

Ameliorating or preventing signatures of aging in humans using natural compounds is an exciting area of research. Here the authors isolate a previously unknown phytochemical from carrots which activates defence mechanisms against oxidative stress and extends lifespan in worms, and improves glucose metabolism, promotes exercise capacity, and protects from frailty at higher age in mice.

Understanding how the immune system’s functionality declines with age is crucial for addressing aging-related health issues. Here, the authors demonstrate that activating TLR5 in the mucosal layer can significantly improve healthspan and longevity, suggesting a novel approach for aging interventions.