Slowing Aging in Primates: The FOXO3 Gene and Its Role in Therapy

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Slowing Aging in Primates: The FOXO3 Gene and Its Role in Therapy
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Chinese Scientists First to Slow Aging in Monkeys Using Genetically Modified Stem Cells with FOXO3 Gene

Chinese researchers have, for the first time, succeeded in slowing the aging process in primates through the use of genetically modified stem cells. The experiment involved introducing cells carrying the so-called "longevity gene" FOXO3 into elderly monkeys, resulting in comprehensive rejuvenation of their bodies.

The therapy reduced chronic inflammation, improved blood composition and the condition of internal organs, strengthened bone tissue, enhanced cognitive functions, and even stimulated the reproductive system. As a result, the biological age of the test subjects effectively decreased by several years. These results serve as the first evidence that such cell technologies can slow aging in primates, paving the way for the development of rejuvenating therapies for humans.

Context and Objective of the Research

As the body ages, its ability to regenerate tissues and organs inevitably declines. The reserve of stem cells, which are responsible for regeneration, becomes depleted, leading to slower healing of injuries and an increase in age-related disorders in organ function. Scientists have long debated whether the reduction of stem cell populations is a cause of aging or merely a consequence of other processes. Previous attempts to slow aging through stem cell transplantation faced several challenges, including poor integration of donor cells, potential immune reactions, or tumor formation.

The new research, conducted by scientists at the Institute of Zoology of the Chinese Academy of Sciences in collaboration with experts from Capital Medical University in Beijing, aimed to overcome these limitations. The researchers set out to determine whether aging could be slowed by genetically "enhancing" stem cells. The results of the work were published in June 2025 in the scientific journal Cell.

Methodology: "Rejuvenating" Stem Cells and Primate Experiment

In the experiment, scientists used a special type of stem cell that was genetically programmed to resist aging. These cells are modified human mesenchymal precursor cells in which the activity of the FOXO3 longevity gene has been enhanced. This intervention enabled the cells to withstand age-related changes and stressors while avoiding transformation into tumor cells.

The trials were conducted on elderly macaques, whose age roughly corresponded to 60-70 years in human terms. Over 44 weeks (about 10 months), these primates were administered intravenous doses of modified cells (approximately 2×106 cells per kilogram of body weight) every two weeks. Throughout the treatment and observation period, no side effects were noted: the transplanted cells integrated well without causing tissue damage or tumor growth.

Results: Rejuvenation of Organs and Functions

Observations demonstrated significant rejuvenation in the primates that received the genetically modified cells. Improvements were noted in several key systems and tissues. In particular, the therapy yielded positive effects in the following areas:

  • Brain and Nervous System: Enhanced cognitive functions (memory) and reduced age-related atrophy of brain tissue.
  • Musculoskeletal System: Strengthened bones, increased bone density, and diminished signs of osteoporosis.
  • Internal Organs and Metabolism: Reduced fibrosis (scarring) in tissues and fat deposits in organs.
  • Blood and Immunity: Rejuvenation of blood cellular composition and improved immune system performance.
  • Reproductive System: Stimulation of gonadal activity and restoration of gamete production.

The rejuvenating changes affected approximately ten primary systems of the body, confirming that genetically modified cells can impact aging comprehensively, enhancing the condition of various organs simultaneously.

Cellular and Molecular Changes

Analyses showed that the treatment influenced the primates' bodies down to the level of cells and molecules. After the course of injections, the number of "old" (senescent) cells, which cause inflammation, decreased, and simultaneously, the proportion of young progenitor cells increased in several tissues (including the brain and reproductive organs). For instance, elderly male macaques experienced revitalized sperm production under the effects of the therapy, which is highly atypical at such an advanced age.

On a molecular level, treated animals demonstrated strengthened internal protective mechanisms: increased genome stability (DNA was damaged less frequently), enhanced protection from oxidative stress, and restored protein balance within cells.

Notably, the activity of genes in over half of the analyzed tissues shifted towards that characteristic of a younger age. For example, the genetic profile of immune blood cells post-therapy matched a profile approximately one-third "younger" than the original, while cells in the brain and ovaries were nearly half as young. Furthermore, biological "clocks" indicated that certain cell types effectively reduced their biological age: neurons by 6-7 years and oocytes by about 5 years.

The Role of Exosomes in Rejuvenation

Researchers identified exosomes—tiny extracellular vesicles released by the introduced stem cells—as critical factors in triggering rejuvenation. Exosomes transport signaling molecules from the transplanted cells to other tissues in the body. As a result, they suppressed chronic inflammation while simultaneously supporting genome and epigenome stability, thereby creating conditions for restoring normal organ function.

Additional experiments revealed that exosomes could independently convey rejuvenating effects. When scientists isolated exosomes from cultured modified cells and injected them into aged mice, the animals exhibited reduced age-related organ damage. Moreover, when these exosomes were added to cultures of human cells (neurons, ovarian and liver cells), signs of rejuvenation were observed in these cells as well. This finding underscores that the transmission of molecular "instructions" through exosomes is one of the crucial mechanisms to reverse aging processes.

Safety and Systemic Effect

An important advantage of the proposed therapy was the absence of serious side effects. Throughout the experiment, the monkeys tolerated the introduction of cells well: there were no instances of tissue damage, inflammatory reactions, or tumor growth. This indicates that genetically modified cells can be safe when properly prepared and monitored.

Moreover, the effects of the treatment were systemic and comprehensive. Unlike many rejuvenating approaches targeting a single specific issue (such as skin condition or the function of a particular organ), cell therapy addressed multiple interconnected systems—nervous, immune, endocrine, musculoskeletal, reproductive, and more. This holistic approach to rejuvenation could prove more effective, given that aging processes affect the whole body simultaneously.

Implications for Aging Science

The results obtained are of great significance for gerontology and biomedicine. It has been demonstrated for the first time that systemic biological aging in primates can be slowed and partially reversed through cell therapy. Previously, such a pronounced rejuvenating effect had only been achieved in experiments on smaller animals (such as mice), and this had not been confirmed in species closely related to humans. Now it has been shown that even the complex organism of a primate can respond with rejuvenation across numerous organs and systems to intervention.

This work supports the notion of aging as a process that can be influenced rather than an inevitable condition. Researchers have laid the groundwork for a new direction in studies where aging is seen as potentially reversible and manageable. The success of genetically modified precursor cells in slowing down aging opens doors for further developments aimed at extending healthy life spans.

Prospects for Human Rejuvenation Applications

Although the research has been conducted on animals, it significantly brings forth the emergence of rejuvenating therapies for humans. If the technology proves to be safe and effective in humans, new treatment methods for age-related diseases and possibly general aging slowdown can be anticipated. Genetically modified cells or their exosomes could potentially become the foundation for personalized "youth injections" capable of restoring tissues and functions in elderly patients.

The results from Chinese scientists are already attracting attention from the biotechnology sector and investors interested in extending life. The development of such cell therapies fits into a global trend towards promoting active longevity.

Challenges and Ethical Aspects

Despite the impressive achievements, the path to the practical application of such a rejuvenation method in humans is fraught with serious challenges. Large-scale clinical trials are needed to confirm the safety and effectiveness of the technology in humans. Additional enhancements may be required—such as using the patient’s own cells to exclude immune rejection. It is also crucial to explore the long-term consequences of the intervention: it remains unknown how lasting the effect of a single course of therapy will be and whether delayed side effects will arise.

Ethical questions take center stage. Rejuvenation procedures of this kind will inevitably spark discussions about the permissible limits of life extension. Society and regulators will need to determine who and under what conditions "eternal youth technologies" may be accessible.

The authors of the study emphasize that their work is merely a first step on a long path. However, this step offers optimism to the scientific community: aging no longer appears to be an insurmountable process, and in the foreseeable future, there is a chance to significantly extend the period of healthy, active life for individuals.

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