A sweeping new study in Science from researchers at The Rockefeller University reframes aging as a coordinated, body-wide process, one that appears to be driven by shared molecular programs rather than isolated tissue decline.
Using single-cell chromatin profiling across 21 tissues in mice, the team generated what may be the most comprehensive atlas to date of how aging reshapes cellular identity and abundance throughout the mammalian body. Their findings suggest that aging is not simply gradual wear-and-tear but instead a regulated and partially synchronized biological process, one that may be more druggable than previously assumed.
“Our goal was to understand not just what changes with aging, but why,” says senior author Junyue Cao, PhD, who heads the Laboratory of Single Cell Genomics and Population Dynamics. “By mapping both cellular and molecular changes, we can identify what drives aging. That opens the door to interventions that target the aging process itself.”
A dynamic shift in cellular composition
The team profiled nearly seven million individual cells from 32 mice at three life stages—young adult (one month), middle-aged (five months), and old (21 months)—using optimized single-cell ATAC-seq to measure chromatin accessibility, a proxy for gene regulatory state.
They identified more than 1,800 distinct cell subtypes, including rare populations not previously characterized. Contrary to the long-standing assumption that aging primarily alters how cells function rather than how many exist, the data revealed something more structural: approximately 25% of cell types showed significant shifts in abundance with age.
Immune cell populations expanded across multiple tissues. In contrast, specialized parenchymal populations—including kidney, muscle, and lung cells—declined.
“The system is far more dynamic than we realized,” Cao says. “And some of these changes begin surprisingly early. By five months of age, some cell populations had already begun to decline. This tells us that aging isn’t just something that happens late in life; it’s a continuation of ongoing developmental processes.”
For clinicians, this finding is particularly relevant. If key cellular declines begin in midlife, the window for preventive intervention may be earlier than typically assumed.
Aging is synchronized across organs
Perhaps the most paradigm-shifting insight is that many of these changes were synchronized across distant organs. Similar cell states expanded or contracted in parallel in multiple tissues.
This argues against a model in which each organ ages independently. Instead, it suggests systemic drivers, potentially circulating factors, that coordinate aging trajectories throughout the body.
“This challenges the idea that aging is just random genomic decay,” Cao explains. “Instead, we see specific regulatory hotspots that are particularly vulnerable.”
Of the 1.3 million genomic regions analyzed, roughly 300,000 showed significant age-associated changes in chromatin accessibility. Around 1,000 of those regions were altered across multiple cell types and tissues, pointing to shared regulatory programs.
Many of these regions were linked to immune signaling, inflammation, and stem cell maintenance—pathways already implicated in age-related disease but now shown to be coordinated at a systems level.
Sex differences in aging biology
Another major finding: approximately 40% of aging-associated cellular changes were sex-dependent.
Females demonstrated broader immune activation with age compared to males.
“It’s possible this could explain the higher prevalence of autoimmune diseases in women,” Cao speculates.
This reinforces a growing recognition in translational research: aging biology—and therefore therapeutic response—may differ substantially between sexes. Clinical trials targeting inflammatory or immunomodulatory pathways in aging populations may need sex-stratified designs to avoid obscuring meaningful differences.
Cytokines as coordinators of aging
By integrating their data with prior studies, the researchers identified immune signaling molecules, particularly cytokines, that could reproduce many of the chromatin and cellular changes observed in aging.
This suggests that systemic inflammatory signals may act as upstream drivers of coordinated aging programs.
Drugs targeting cytokine signaling pathways already exist for autoimmune and inflammatory diseases. The implication is provocative: therapies currently used for immune disorders could potentially be repurposed or refined to modulate aging trajectories.
“We’ve identified the vulnerable cell types and molecular hotspots,” Cao says. “Now the question is whether we can develop interventions that target these specific aging processes. Our lab is already working on that next step.”
A shift from disease-centric to aging-centric medicine
Clinicians are increasingly confronted with multimorbidity in older adults, cancer alongside cardiovascular disease, metabolic dysfunction alongside neurodegeneration. This atlas provides mechanistic support for the idea that these conditions may share upstream aging programs.
Rather than treating each pathology in isolation, future strategies may target common molecular circuits that underlie multiple diseases.
The study also highlights that aging is not purely degenerative; it is patterned, coordinated, and in some cases predictable. That predictability is what makes it potentially actionable.
If validated in humans, these findings could reshape how we think about prevention—not just delaying disease onset, but intervening at the level of systemic aging biology.
