Researchers at The Rockefeller University have created a detailed cellular atlas of aging by analyzing nearly 7 million cells from 21 organs in mice. The study reveals that aging begins earlier than previously thought and occurs in a coordinated manner throughout the body. Findings highlight differences between males and females, along with potential targets for anti-aging therapies.
A new study published in Science provides an in-depth look at how aging affects mammalian tissues. Scientists at The Rockefeller University, led by Junyue Cao, examined cells from 32 mice at three life stages: one month (young adult), five months (middle-aged), and 21 months (elderly). Using a refined single-cell ATAC-seq method, the team mapped DNA accessibility in nearly 7 million individual cells across 21 organs, identifying over 1,800 distinct cell subtypes.
The analysis showed that about one quarter of cell types change in abundance over time, challenging the view that aging primarily alters cell function rather than numbers. Declines in certain muscle and kidney cells occurred sharply, while immune cells expanded. These shifts began as early as five months of age, indicating that aging extends developmental processes rather than starting late in life.
Notably, many changes synchronized across organs, suggesting shared signals, possibly circulating factors in the bloodstream, coordinate the process. Nearly half of the age-related shifts differed between males and females; for instance, females exhibited broader immune activation with age. "It's possible this could explain the higher prevalence of autoimmune diseases in women," Cao speculates.
The researchers also identified aging-related alterations in about 300,000 of 1.3 million genomic regions analyzed, with around 1,000 shared across cell types. These hotspots, linked to immune function, inflammation, and stem cell maintenance, point to specific regulatory vulnerabilities. "This challenges the idea that aging is just random genomic decay," Cao says. Comparisons with prior research suggest cytokines trigger similar changes, opening avenues for drugs to modulate them and potentially slow aging body-wide.
"Our goal was to understand not just what changes with aging, but why," Cao explains. The full atlas is publicly available at epiage.net, serving as a foundation for future interventions. The work was led by graduate student Ziyu Lu and appears in Science (2026; 391(6788)), DOI: 10.1126/science.adw6273.
