As we age, our bodies gradually lose their ability to repair and regenerate. Imagine a bustling city where construction workers (stem cells) are constantly fixing and building new structures. But as time goes on, fewer workers show up, and the city starts to crumble. This is what happens in our bodies—our stem cells dwindle, making it harder for tissues to heal and maintain balance. This decline is a hallmark of aging and a key driver of age-related diseases. Scientists have long puzzled over whether this stem cell decline is the root cause of aging or just a side effect. Meanwhile, attempts to use stem cell transplants to reverse aging have been stymied by tricky biological hurdles, like getting the cells to survive and integrate into the body without causing dangerous side effects like tumors.

Beijing, June 13, 2024 – In a groundbreaking study published in Cell, researchers from the Chinese Academy of Sciences and Capital Medical University have cracked a major code in the fight against aging. Using cutting-edge synthetic biology techniques, they’ve reprogrammed the genetic pathways linked to longevity, creating a new type of human stem cell called senescence-resistant mesenchymal progenitor cells (SRCs). These cells are like supercharged construction workers: they’re resistant to aging, can resist stress, and won’t turn into tumors. What’s even more remarkable is that these cells have successfully reversed multiple signs of aging in primates—our closest biological relatives. This is the first time we’ve seen such comprehensive rejuvenation in a species so similar to humans through stem cell therapy.

The team conducted a 44-week experiment on elderly crab-eating macaques, which are physiologically similar to humans in their 60s and 70s. The macaques received biweekly intravenous injections of SRCs at a dose of 2×10？ cells per kilogram of body weight. Throughout the study, the researchers kept a close eye on the animals’ health. They found no adverse effects—no fever, immune overreactions, or weight loss. Detailed histopathological assessments also confirmed that the transplanted cells didn’t cause tissue damage or tumors. In other words, the SRCs were not only effective but also safe.

But the real magic happened when the researchers looked at the broader impact of the SRCs. Imagine a city not just fixing one broken bridge but revitalizing its entire infrastructure. The SRCs triggered a multi-system rejuvenation, reversing key markers of aging across 10 major physiological systems and 61 different tissue types. The treated primates showed improved cognitive function, and tissue analyses revealed a reduction in age-related degenerative conditions like brain atrophy, osteoporosis, fibrosis, and lipid buildup. At the cellular level, the SRCs reduced the number of senescent cells, suppressed inflammation, and boosted the populations of progenitor cells in neural and reproductive tissues. They even stimulated sperm production. Molecularly, the SRCs enhanced genomic stability, improved response to oxidative stress, and restored protein balance. Over 50% of the tissues examined showed a reversal of aging-related gene expression networks to a younger state. Single-cell analyses revealed significant reversal of age-related gene expression profiles in peripheral blood cells (33%), the hippocampus (42%), and ovarian tissue (45%). Machine learning-based aging clocks estimated that the biological age of immature neurons was turned back by 6-7 years, and that of oocytes by 5 years.

So, how did the SRCs work their magic? The researchers discovered that tiny packets called exosomes, released by the SRCs, were the primary agents of rejuvenation. These exosomes suppressed chronic inflammation while preserving the integrity of the genome and epigenome. When isolated SRC exosomes were given to aged mice, they significantly reduced organ degeneration. In vitro studies showed that these exosomes could rejuvenate various human cell types, including neurons, ovarian cells, and hepatocytes. This finding suggests that exosome signaling could be a fundamental pathway for reversing aging.

These findings position SRC therapy as a groundbreaking intervention for multi-system aging. It offers two major breakthroughs: First, it provides the first primate-level evidence of safe cell therapy, with long-term administration at clinically relevant doses showing no immunogenicity or tumorigenicity. This addresses a crucial barrier to translating the therapy to humans. Second, it demonstrates multi-system geroprotective efficacy, restoring function across interdependent physiological systems like the nervous, reproductive, and immune systems. This holistic approach surpasses single-target therapies and aligns with the conserved pathophysiology of aging between primates and humans. Beyond laying a solid preclinical foundation for human trials, this work redefines anti-aging strategies through a unified, systems-level approach to combat age-related multimorbidity.

DOI: https://doi.org/10.1016/j.cell.2025.05.021

SRC Reverses Lipid Buildup in Aged Monkeys' Skeletal Muscle: Control Group (Left); SRC-Treated Group (Right). (Image by LIU Guanghui's lab)