Turquoise killifish are naturally short-lived vertebrates that serve as a model system for aging. The authors show that killifish exhibit age-related transformation in the immune system, which rapidly develops inflammation, genome instability and functional decline.

Epigenetic clocks are promising biomarkers of biological aging but require longitudinal evaluation. In this longitudinal study, the authors evaluated whether temporal acceleration of multiple epigenetic clocks was associated with mortality, and report that faster increases in several clocks were linked to higher risk of death, independent of baseline epigenetic age and other confounders.

By integrating microglial transcriptomics with CSF proteomics, this study reveals protein markers that distinguish early and late Alzheimer’s disease and that have the potential to improve disease tracking and prediction.

Subcellular mRNA localization shapes microglial morphology and function. Using multiplexed error-robust fluorescence in situ hybridization, Henze et al. identify distinct transcript patterns associated with microglial states across young and aged mouse brains.

Investigating how aging predisposes individuals to a higher metastatic risk, the authors identify that extracellular vesicles secreted by senescent hepatocytes carry miRNAs that enhance metastatic potential in tumor-bearing aged mice, with relevance for older adults with cancer.

Young, cognitively normal APOE4 mice display hippocampal network hyperactivity that predicts later memory decline. This phenotype is driven by neuronal APOE4 expression, which causes hyperexcitability of hippocampal neurons and can be reversed by targeting Nell2.

The dynamics of breast tissue aging are characterized by imaging mass cytometry of over 500 reduction mammoplasties, revealing nonlinear loss of cellularity and a compositional shift favoring inflammation.

To dissect lncRNA functions in aging, here the authors perform a CRISPRi-based single-nucleus multiomics screen systematically perturbing 32 aging- and senescence-associated lncRNAs and measuring matched changes in gene expression and chromatin accessibility. They pinpoint a role for HOTAIRM1 linked to DNA repair-related gene control and show that replenishing HOTAIRM1 in mouse lungs reduces fibrosis.

Turquoise killifish are naturally short-lived vertebrates that serve as a model system for aging. The authors show that killifish exhibit age-related transformation in the immune system, which rapidly develops inflammation, genome instability and functional decline.

Epigenetic clocks are promising biomarkers of biological aging but require longitudinal evaluation. In this longitudinal study, the authors evaluated whether temporal acceleration of multiple epigenetic clocks was associated with mortality, and report that faster increases in several clocks were linked to higher risk of death, independent of baseline epigenetic age and other confounders.

The World Health Organization’s integrated care for older people (ICOPE) model is person-centered and focuses on functional abilities and well-being. Here, Bruno Vellas introduces the efforts of the French government to deploy a national-level ICOPE care program, and describes how they can serve as a template for implementing similar nationwide programs elsewhere.