Single-cell transcriptomic profiling of young and old mouse brains following heterochronic parabiosis shows regulation of several canonical hallmarks of aging by a shift in age-induced changes of the transcriptome in a cell-type-specific manner.

In vivo partial reprogramming by expression of Oct4, Sox2, Klf4 and c-Myc has been shown to have rejuvenating effects in a mouse model of premature aging. Here, the authors report that longer-term partial reprogramming regimens are safe and effective in delaying age-related changes in physiologically aged mice.

Osteoarthritis (OA) leads to joint degeneration, including the progressive loss of articular cartilage. Here the authors show that kindlin-2 expression is decreased in degenerate cartilage and that its overexpression decelerates the progression of OA in mice.

Circulating factors play an important role in tissue aging. Here, the authors show that serum EV subpopulations and cargoes remodel with age and that EVs from young mouse serum rejuvenate aged skeletal muscle.

Ferrari-Souza et al. show that the APOEε4 allele potentiates the deleterious effects of Aβ on the longitudinal accumulation of tau tangles in neocortical brain regions, via tau phosphorylation, which coincides with brain atrophy and clinical decline.

A single-cell transcriptomic analysis by Lau et al. reveals a homeostatic–chemotactic–phagocytic state transition in microglia upon IL-33 stimulation, identifying VCAM1 as a key regulator of microglial chemotaxis by sensing Aβ plaque-associated ApoE.

Pereira, Kumar et al. identify cerebrospinal fluid DOPA decarboxylase as a promising biomarker for Parkinsonian disorders that may be used for early preclinical detection of Parkinsonian disorders as well as determining the risk of conversion to Lewy body disease.

Lamin A/C protects alveolar macrophages against nuclear envelope rupture and DNA damage, but it erodes during aging. Lack of lamin A/C leads to senescence and an aging signature, resulting in vulnerability to influenza virus and lung cancer growth.

Li et al. provide a transcriptional and epigenetic characterization of microglia in aging mice brain by developing a three-round depletion–repopulation (3xDR) model to study aged microglia in non-aged brain, giving insights into the molecular mechanism underlying microglia aging.

Anerillas et al. provide a strategy to eliminate senescent cells that leverages on their secretory needs. Inhibiting YAP–TEAD triggers endoplasmic reticulum stress that eliminates senescent cells from several tissues, improving age-related fibrosis.

Given the unique requirements of older adults, age-friendly product design is becoming increasingly important to promote independence and enhance quality of life. The Global Centre for Modern Ageing calls for a comprehensive, standardized and evidence-based assessment process to incorporate the perspectives of older adults into the design process.

The intestinal epithelium serves as a barrier that facilitates interaction between intrinsic and environmental factors. Aging is accompanied by the gradual deterioration of this barrier. We postulate that barrier dysfunction results from defects in epithelial membrane trafficking that exacerbate age-related metabolic imbalances. Herein, we integrate barrier integrity, protein homeostasis, membrane trafficking and intracellular lipid sensing into an age-determining mechanism.

Aging is a major risk factor for vascular disease. Increased levels of milk fat globule-EGF factor 8 (MFG-E8) are associated with many age-related arterial changes, but the mechanisms remain unclear. We propose that these detrimental effects may result from medin, a fragment of MFG-E8 that forms a highly common vascular amyloid.