Scientists at The Rockefeller University in New York have produced the most detailed cellular atlas of aging ever assembled, profiling approximately seven million individual cells drawn from 21 organs in mice. The study, published on February 28 in the journal Science, reveals that aging is not a process of random genomic decay but rather a coordinated biological program driven by systemic signals that reshape cell populations across the entire body simultaneously. The research was led by Junyue Cao, head of the Laboratory of Single-Cell Genomics and Population Dynamics, with graduate student Ziyu Lu serving as lead author.
The team employed an optimized technique called EasySci-ATAC, a form of single-cell chromatin accessibility sequencing that examines how DNA is packaged inside individual cells. By analyzing which regions of the genome are open and actively being read, the researchers mapped the functional state of each cell across three age groups of 32 mice, ranging from one month to 21 months old. The method proved remarkably efficient, with Cao noting that most large-scale atlases require dozens of laboratories, while his team accomplished the work with a single lab.
The atlas identified 536 distinct cell types and 1,828 finer-grained subtypes, many of which had never been previously characterized. Roughly one quarter of all cell types showed significant population shifts with age, with muscle, kidney, and lung cells displaying the steepest declines. In contrast, immune cells expanded dramatically across multiple organs as animals grew older, a pattern that was particularly pronounced in females. The researchers found that approximately 40 percent of all aging-associated cellular changes were sex-dependent, a finding they believe may help explain why autoimmune diseases are more prevalent in women.
One of the most striking discoveries was that identical cellular states appeared and declined in parallel across distant, unrelated organs. This coordinated aging pattern suggests that circulating factors in the blood, such as cytokines and other immune signaling molecules, orchestrate cellular changes throughout the body rather than each organ aging independently. The study also challenged conventional assumptions about when aging begins, with some cell populations already showing measurable decline by five months of age in mice, roughly equivalent to middle age in humans.
Of the 1.3 million genomic regions analyzed, approximately 300,000 showed significant aging-related changes in chromatin accessibility. About 1,000 of these alterations appeared consistently across multiple cell types, pointing to shared regulatory programs linked to immune signaling, inflammation, and stem cell maintenance. These shared vulnerable genomic regions represent potential targets for therapeutic interventions that could produce body-wide anti-aging benefits rather than organ-limited effects.
The complete atlas has been made freely available to the global research community through the public database epiage.net. The research was funded by the National Institutes of Health through grants from the National Human Genome Research Institute and the National Institute on Aging. Scientists in the field have described the work as a foundational resource that could accelerate the development of biomarkers for detecting biological aging before clinical symptoms emerge, as well as precision medicine approaches that account for sex-specific differences in how the body ages over time.
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