Aging May Be a Program, Not a Breakdown, Rockefeller Biologist Argues

For decades, the biology of aging has been explained by wear and tear: molecules, cells and organs accumulate damage, repair mechanisms fall behind, and decline follows. In a Q&A published by Quanta Magazine on August 14, cell biologist Junyue Cao argues that this picture is inaccurate.

Not wear and tear, but a program

Cao, who heads the Laboratory of Single-Cell Genomics and Population Dynamics at Rockefeller University, describes aging as a stepwise, orderly process rather than random decay. “The destruction of the system is programmed at a very early stage,” he told Quanta contributing writer Ingrid Wickelgren. His lab has outlined discrete stages of aging, comparable to embryonic development, defined by changes in molecular signals and specific cell populations. In humans, the process likely begins before age 30.

21 million cells across five life stages

In one series of experiments, the team processed 21 million cells from 14 tissues and organs of about 50 mice at five life stages — 3, 6, 12, 16 and 23 months, roughly 20, 30, 50, 60 and 75 years in humans — and measured the expression of 20,000 genes per cell. They identified 536 main cell types and 1,828 subtypes, but only about a quarter of the subtypes shifted strongly with age.

Early on, certain fat and muscle cells and two immature brain cell types with regenerative capacity are lost. Between 6 and 12 months in mice — the human 30s and 40s — cells that maintain tissues fall sharply, among them tenocytes, colon smooth muscle cells and kidney epithelial cells. From about 12 months, depletion gives way to expansion led by immune cells; by 16 months, aging-associated immune cells proliferate, and Cao links them to rising risks of heart disease, arthritis, cancer and chronic respiratory illness.

A code, not random damage

Two papers published in Science in 2025 and 2026 point to a radical redistribution of the body's cells with age. Cao's team identified 280,000 genomic regions that open or close reproducibly in specific cell types during aging — the same regions each time, which random damage would not produce. Internal programs and secreted molecules called cytokines appear to drive the changes. Cao likens aging to a tree that sheds its leaves within about two weeks each autumn.

Why timing matters

Human data fit the pattern: protein signatures in blood shift markedly between the mid-40s and late 50s, and researchers have documented “abrupt aging” in middle age. Cao's lab has identified rare vulnerable cell types that could be targets for anti-aging interventions; because regenerative capacity declines before middle age, he argues, efforts to slow aging should start early.