The repair and regenerate abilities of our bodies gradually decreased with age. Imagine a bustling city where construction workers (stem cells) are constantly fixing and building new structures. However, with the passage of time, fewer workers show up, and the city begins to crumble. This is precisely what happens in our bodies—stem cells dwindle, making it more difficult for tissues to heal and maintain homeostasis. This decline is a hallmark of aging and a key driver of age-related diseases. For years, scientists have debated whether the decline of stem cells is the root cause of aging or merely a side effect. Meanwhile, attempts to use stem cell transplants to reverse aging have been hindered by tricky biological challenges, such as getting the cells to survive and integrate into the body without causing dangerous side effects like tumors.
In a study published in Cell on June 13, 2025, researchers from the Chinese Academy of Sciences and Capital Medical University have made a breakthrough in the fight against aging. Utilizing cutting-edge synthetic biology techniques, they reprogrammed the genetic pathways associated with longevity, creating a new type of human stem cell called senescence-resistant mesenchymal progenitor cells (SRCs). These cells are like supercharged construction workers: resistant to aging and stress, and do not turn into tumors. The more remarkable is that these cells have successfully reversed multiple signs of aging in non-human primates—our closest biological relatives. This is the first time such comprehensive rejuvenation has been achieved in a species so similar to humans through stem cell therapy.
They conducted a 44-week experiment on elderly macaques in this study, which are physiologically equivalent to humans in their 60s and 70s. The macaques received biweekly intravenous injections of SRCs at a dose of 2 × 10⁶ cells per kilogram of body weight. Throughout the study, the researchers closely monitored the animals’ health. They found no adverse effects—no fever, immune overreactions, or weight loss. Detailed histopathological assessments also confirmed that the transplanted cells did not cause tissue damage or tumors. In other words, the SRCs were not only effective but also safe.
However, the real magic happened when the researchers examined the broader impact of the SRCs. Imagine a city not just fixing one broken bridge but revitalizing its entire infrastructure. The SRCs triggered 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 such as brain atrophy, osteoporosis, fibrosis, and lipid buildup. At the cellular level, the SRCs reduced the number of senescent cells, suppressed inflammation, and increased the populations of progenitor cells in neural and reproductive tissues. They even stimulated sperm production. Molecularly, the SRCs enhanced genomic stability, improved the response to oxidative stress, and restored proteostasis. Over 50% of the tissues examined showed a reversal of aging-related gene expression networks to a younger state. Single-cell analyses revealed a 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.
Then, how about the mechanisms of the SRCs’ remarkable effects? The researchers found that the SRCs release tiny packets known as exosomes, which play a crucial role in the rejuvenation process. These exosomes contain molecules that not only suppress chronic inflammation but also maintain the stability of the genome and epigenome. There was a significant reduction in organ degeneration in mice with exosomes administration. The in vitro studies demonstrated that these exosomes show rejuvenate ability in several human cell types, such as neurons, ovarian cells, vascular endothelial cells, and hepatocytes. This suggests that exosome signaling may be a key mechanism in reversing the aging process.
These discoveries position SRC therapy as a promising intervention for multi-system aging. It offers two major breakthroughs: First, this study provides the first primate-level evidence supporting the safety of cell therapy, demonstrating that long-term administration at clinically relevant doses elicits no immunogenicity or tumorigenicity. This finding overcomes a major translational barrier for human applications. Second, the results reveal broad geroprotective effects across multiple physiological systems—including the nervous, reproductive, and immune systems—highlighting a capacity to restore function in interdependent aging processes. Such a multi-system approach surpasses conventional single-target interventions and aligns with the conserved aging mechanisms shared by primates and humans. Beyond establishing a robust preclinical foundation for human trials, this work advances anti-aging research by proposing a unified, systems-level strategy to counteract age-related multimorbidity.
DOI：10.1016/j.cell.2025.05.021