Geroprotective interventions for healthy aging

Accumulation of senescent retinal pigment epithelial (RPE) cells is associated with retinal aging and disease. Here, authors identify Bst2 as a membrane-localized marker upregulated in senescent RPE cells and develop an antibody-pluggable drug delivery platform targeting Bst2-expressing cells for targeted senotherapy.

Culos, Manas et al. construct machine learning surrogate frailty metrics from activity data collected in a nominally intrusive manner. They show that a limited amount of activity data is necessary to model frailty metrics allowing for an increased proliferation of their application along with a robust source of data for other age-related outcomes.

Aging impairs the regenerative capacity of skeletal muscle stem cells. Here, the authors identify a stem cell-specific fibronectin splice variant and show that its cell-autonomous secretion through the TGFβ1-Smad3-Srsf1 pathway can be targeted to restore tissue repair in aged mice

Takeuchi et al. conduct a randomized controlled trial to assess the impact of oral exercise frequency on frailty in older adults. They find that performing oral exercises three times daily, three days per week significantly improves frailty status, offering a practical approach for prevention.

Li et al. analyze multi-scale phenotypes to investigate heterogeneity in multi-organ aging patterns. They find that accelerated aging in organs such as the cardiovascular system, brain, kidneys, bone, and metabolism is associated with organ-specific links to lifestyle factors, health status, and cardiovascular risk.

Hypoxic conditioning—controlled, brief and repeated exposure to moderate levels of low-oxygen air—is safe in people with Parkinson’s disease, with participants reporting mild, short-term improvement in Parkinson’s symptoms.

Wang, Cai, Li et al. examine how knee osteoarthritis (KOA) drives cognitive decline through hippocampal fimbria shrinkage and peripheral inflammation. Fimbria volume mediates pain-related memory loss while elevated interferon-gamma protects against dementia, enabling early risk detection.

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.