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In the largest and most detailed protein portrait of human organ aging to date, a team led by researchers from the Chinese Academy of Sciences and Sichuan University has published a landmark study in Cell. Using ultra-sensitive mass spectrometry and artificial intelligence, the scientists tracked more than 12,700 proteins across 13 tissues from 76 individuals aged 14 to 68, creating the first “molecular movie” of how our organs grow old. The work reveals that faulty protein quality control—especially in blood vessels—lies at the heart of systemic aging, and that molecules released by aging arteries can accelerate decline in distant organs.

Aging has long been viewed as a patchwork of independent cellular clocks; this study shows it is better understood as a single, interconnected network orchestrated by the vascular system. By mid-life, the aorta—the body’s largest artery—begins pumping out a distinct set of “senoproteins”, including GAS6, that act like courier-delivered aging instructions. When the team injected GAS6 into healthy middle-aged mice, the animals’ grip strength, balance and vascular health deteriorated within weeks. 

The researchers uncovered three overarching signatures of aging. First, the central dogma frays: the tight link between RNA instructions and the proteins they encode loosens with age, starving cells of the right tools at the right time. Second, the cellular toolkit for making, folding and disposing of proteins—ribosomes, chaperones and proteasomes—declines across nearly every organ. Third, toxic protein such as amyloids, immunoglobulins and complement factors accumulate, knitting together an inflammatory web that constitutes the molecular cornerstone of inflammaging. Among the most pervasive culprits is Serum Amyloid P (SAP), identified as the top “universally up-regulated pan-tissue aging protein.” In laboratory dishes, SAP alone was sufficient to push young blood-vessel cells into an aged, inflammatory state.

To translate these molecular patterns into practical age-measuring tools, the team built an AI-driven “proteomic aging clocks” for each tissue. The clocks show that the adrenal glands and aortas are the first organs to drift off course, around age 30, hinting that early hormonal or vascular changes may set the tempo for the rest of the body. A dramatic “molecular cascade storm” between ages 45 and 55 marks the transition from piecemeal to systemic aging; the aorta’s protein profile is the most violently remodeled during this window and its secreted factors mirror changes in circulating blood, confirming its role as the body’s “senohub”.

Beyond GAS6, the study fingered four additional vascular-derived proteins—GPNMB, COMP, HTRA1 and IGFBP7—that can independently trigger cellular senescence. Injecting GPNMB into young mice recapitulated whole-body aging. These findings cement the principle of “spreading senescence”, in which a single aging organ transmits aging signals through the bloodstream.

Collectively, the work establishes a “Protein Imbalance–Vascular Hub” model that reframes aging from a collection of failing cells to a communicable, organ-level phenomenon. The authors are now translating their atlas into non-invasive blood tests that assess the biological age of each organ and exploring protein-correcting therapies that could extend healthy lifespan by restoring protein balance where it begins—in the vessels that feed every tissue.

The paper, “Comprehensive Human Proteome Profiles Across a 50-Year Lifespan Reveal Aging Trajectories and Signatures” was published in Cell on July 25.

GAS6 rises with age in human aorta: young (left) vs. aged (right) (Image by LIU Guanghui and ZHANG Weiqi’s labs)

Contact：

ZHANG Weiqi

Beijing Institute of Genomics of Chinese Academy of Sciences (China National Center of Bioinformation)

Email: zhangwq@big.ac.cn