Genetically modified human cells have achieved a remarkable feat by regenerating several organs in aged primates, as if time had been partially reversed for their tissues. This experimental breakthrough, although preliminary, outlines a future where the fight against pathological aging could rely on our own amplified biological mechanisms.
This study, conducted by the Chinese Academy of Sciences, marks a significant milestone by demonstrating for the first time multi-organ rejuvenation in a non-human primate. Researchers administered a particular type of human stem cells, engineered to resist cellular aging, to aged macaques. The results observed after several weeks of treatment go beyond the scope of a simple isolated improvement.
The cellular mechanism of rejuvenation
The approach relies on optimizing a key gene, FOXO3, known for its involvement in longevity. Scientists introduced specific mutations into this gene within human stem cells, a modification aimed at significantly strengthening their natural resistance to stress and senescence, that state where aging cells stop dividing and become harmful to their environment.
These boosted cells, once prepared, were delivered intravenously to macaques aged 19 to 23 years (equivalent to 60 to 80 years for a human), through repeated infusions over a long period. The treatment was administered according to a precise schedule spanning 44 weeks, replicating conditions close to a potential future human therapeutic protocol. This extended duration allowed observation of the cumulative effects of the cell therapy on the primates' entire organisms. No serious adverse effects, such as immune rejection or tumor formation, were reported by the researchers during this period.
Tissue analysis subsequently revealed that the treatment had significantly reduced the presence of the infamous "zombie cells," incapable of dividing, and decreased markers of chronic inflammation. These two fundamental characteristics of aging showed notable improvement, while genome stability appeared better preserved in the treated animals compared to the control group.
Observed effects on organs and functions
The most striking improvements concerned the nervous system, where researchers noted clear progress in memory tests assessing recognition ability. The treated macaques demonstrated an increased capacity to memorize and retrieve objects, indicating a tangible improvement in their cognitive functions that tended to approach those of young individuals.
Imaging examinations confirmed a tangible slowing of brain atrophy and an encouraging restoration of neural connections. The brain structure of the treated aged animals indeed showed characteristics approaching those observed in young individuals, with preserved neuronal complexity and improved synaptic density in several key brain regions.
The skeletal system also benefited from the intervention, with measurable bone remineralization that appears to reverse age-related bone loss. The dental condition of the treated animals also improved, approaching that of young individuals. In-depth analysis of about sixty tissue types ultimately revealed extensive rejuvenation: more than half of the examined tissues, including the hippocampus, colon, and reproductive tissues, showed younger genetic signatures. Biological clocks based on artificial intelligence estimated a rejuvenation of six to seven years for certain cell types.
Going further: What is cellular senescence?
Senescence is a particular state in which an aging cell permanently stops its division cycle, without immediately dying. These senescent cells gradually accumulate in our tissues over time, like a residue of biological wear. Their presence becomes increasingly significant with advancing age, contributing to the functional decline of organs.
Far from being silent, these cells become active and release a cocktail of pro-inflammatory molecules that disrupt their environment. This secretion, called the senescence-associated secretory phenotype, alters the functioning of neighboring healthy cells and degrades tissue architecture. It creates a microenvironment unfavorable to regeneration and the maintenance of tissue homeostasis.
Senescence is now considered one of the fundamental drivers of aging and the onset of many associated pathologies. This is why strategies aimed at specifically eliminating these cells, or neutralizing their harmful effects, constitute an extremely promising research avenue for preserving health and potentially delaying the onset of age-related diseases.
What is the role of the FOXO3 gene in longevity?
FOXO3 is a gene considered a "longevity gene," whose specific variants are statistically more frequent in centenarians worldwide. It codes for a protein that acts as a transcription factor, binding to DNA to regulate the expression of many other genes. Its activity is important for cell survival and integrity in the face of aggression.
This protein orchestrates the response to cellular stress by activating antioxidant defenses and promoting autophagy, the process of recycling defective cellular components. It thus enables the cell to better resist oxidative damage and maintain a healthy intracellular environment by eliminating dysfunctional elements that accumulate over time.
It also plays a role as a guardian of the genome by facilitating the repair of damaged DNA and regulating cellular metabolism. By artificially strengthening FOXO3 activity, researchers therefore hope to equip cells with more resistant armor against aging mechanisms, enhancing their innate maintenance and repair capabilities.
Article author: Cédric DEPOND