This Perspective describes the blueprint, challenges and potential solutions for the transformation of Alzheimer’s disease clinical care pathway with biomarker-guided and digitally facilitated detection and intervention at early disease stages.

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.

Cutler et al. found that age predicted individuals’ likelihood to engage in prosocial behaviors such as social distancing during COVID-19 and charitable donations. Older adults across the world were more willing to help but also demonstrated stronger in-group preferences, donating less to international charities.

Arthur et al. report the biochemical and proteomic (SomaLogic) profiling of plasma and CyTOF immunophenotyping of peripheral blood mononuclear cells from 71 individuals with COVID-19 or other inflammatory pulmonary diseases, and 148 healthy donors aged 25–80 years old. The Resource reveals unique determinants of COVID-19 disease relative to healthy aging and other pulmonary disorders.

Frailty of the aged brain may relate to impaired vascular control and limitations in energy supply. The authors report an age-related decrease in responsivity of brain microvessels, accompanied by a decrease in vessel density and loss of vascular mural cell processes.

Dietary supplementation of the clinical PI3K inhibitor alpelisib (Piqray) extends the lifespan of male and female mice and is associated with greater strength and balance but reduced bone mass and mild hyperglycaemia.

Older people have suboptimal responses to primary series vaccines, which can place them at risk for adverse coronavirus disease 2019 outcomes. Here the authors show that booster vaccines provide a substantial increase in antibody levels in the short term but that there is significant waning 100 d after booster shots.

Impaired CD4⁺ T cell responses in older adults correlate with weaker humoral and cellular immunity as well as reduced systemic reactogenicity following mRNA coronavirus disease 2019 vaccination, thus highlighting the impact of T cell aging on vaccine effectiveness.

Baez-Lugo et al. show that increased functional brain connectivity between default mode network and amygdala in resting state after high emotional events is associated to higher anxiety, rumination and negative thoughts in older adults.

This study identifies a new germline-to-soma aging signal tuned by mating in Caenorhabditis elegans. The authors find that germline piRNAs influence longevity and somatic maintenance by transcriptionally regulating germline-to-soma Hedgehog signaling.

There is tremendous interest in the development of drugs that target senescent cells (‘senolytic’ drugs) to treat a range of age-related morbidities. However, studies in mice that demonstrate impaired tissue repair following clearance of senescent cells raise questions about the potential risks of senolytic therapies. Closer examination of the available studies reveals the hopeful possibility of a ‘therapeutic window’ in which these risks can be minimized.