Volume 5 Issue 1, January 2025

Geriatric day hospitals were originally set up to provide rehabilitation and social care for older adults. Román Romero-Ortuño highlights how in Ireland, geriatric day hospitals have evolved into hubs for integrated care, which prevents avoidable hospital admissions and promotes independence for older adults.

Although the emerging field of geroscience holds great promise for identifying new approaches to improve healthspan, several risks of the current framework are underappreciated. Long time horizons, challenges in identifying causality-driven surrogate biomarkers of aging, and the potential for biological trade-offs and antagonistic effects across various timescales mean it will be hard to know when such interventions have a net benefit. We propose eight strategies to mitigate these risks going forwards.

Chronic stress markedly affects health, but the underlying mechanisms have remained unexplored. Using two stress paradigms (simulating bullying and confinement), Lyons and colleagues now demonstrate that even a brief, single-month exposure to stress can induce neuronal senescence in mice.

Accelerated brain aging is a risk factor for dementia, and resilience to normal brain aging is associated with cognitive preservation. Liu and colleagues explore plasma proteomic changes associated with brain aging and identify peaks of brain aging-related protein changes in middle-aged or older adults.

A chimeric peptide designed to recruit immune cells has been shown to enhance the ‘coupling’ between senescent cells and natural killer cells to promote immune clearance of senescent cells for restoration of tissue homeostasis in liver fibrosis, lung injury, cancer and even natural aging in mice.

A study examined trends in intrinsic capacity, a comprehensive measure of cognitive, locomotor, psychological and sensory capacities that was recently developed by the World Health Organization. The results indicate that older adults in England today seem to be experiencing far higher levels of physical and mental functioning than did previous generations at the same age.

Senescent cells can exert detrimental effects, yet beneficial roles of p16 highly expressing cells have been reported in contexts such as wound healing. Enhancing our understanding of the heterogeneity of senescence in vivo, Gasek et al. identify a distinct and detrimental p21 highly expressing cell population induced upon wound healing.

Ming, Yang, Huang et al. design a chimeric matchmaker peptide, which targets a senescent cell-specific surface marker and modifies the cell surface with polyglutamic acid. This promotes interactions with natural killer cells and senescent cell clearance in liver fibrosis, lung injury, cancer and natural aging.

Exploring the molecular consequences of exposing mice to social stress, Lyons et al. identify that hippocampal and cortical neurons acquire features of senescence, identifying a mechanism through which the social environment may contribute to aging.

Knee osteoarthritis has a sex-specific phenotype with post-menopausal persons experiencing the highest incidence. Here the authors investigate the underlying mechanisms in a mouse model of menopause and find that the loss of 17β-estradiol and progesterone enhanced susceptibility to senescence, extracellular matrix disassembly and cartilage degradation.

Intrinsic capacity includes a person’s mental and physical capacities. The authors examined cohort trends in intrinsic capacity in two large English and Chinese studies. They report that more recently born participants entered older ages with markedly higher levels of functioning, while subsequent age-related declines were somewhat delayed.

Using proteomics and imaging data from UK Biobank, the authors identified multiple circulating proteins associated with brain aging and discovered undulating age-related changes in the plasma proteome, with peaks occurring at 57, 70 and 78 years of age.

The authors score and rank the adaptation to societal aging across 143 countries using a newly developed index called the Global Aging Society Index, which may be helpful to identify targets for the development of policies and programs to enhance the likelihood that older people will age successfully.

The authors describe how aging rewires the cellular composition of mouse mammary tissues and impacts the transcriptomic and epigenomic programs of mammary epithelial, fibroblast and immune cells, identifying shared signatures of aging and cancer.

Arora et al. present AgeXtend, an explainable artificial intelligence-based platform that leverages bioactivity data to predict geroprotectors. They validate potential geroprotectors identified using this platform in yeast, worm and senescence assays.

Exploiting the selective accumulation of lipofuscin in senescent cells, the authors developed a targeted senolytic platform. As proof of concept, they show that selective delivery of dasatinib elicits senolysis with minimal toxicity, in vitro, in organoids and in mice.