Researchers at Shanghai’s Institute of Nutrition and Health develop senescence-resistant stem cells by integrating the FOXO3 longevity gene into human mesenchymal progenitor cells, which then release exosomes that counteract cellular aging and inflammation in macaques, improving cognitive, skeletal and reproductive functions.
Key points
Engineering of mesenchymal progenitor cells with constitutive FOXO3 activation to resist senescence.
Intravenous delivery of SRCs in aged macaques leading to exosome-mediated restoration of epigenetic and inflammatory biomarkers.
Observed improvements in cognition, bone density and reproductive function without adverse effects.
Why it matters:
This demonstration of systemic, gene-engineered cell therapy reversing aging hallmarks in primates marks a significant leap toward translational longevity medicine.
Q&A
What are senescence-resistant cells?
How do exosomes contribute to rejuvenation?
Why use macaques for this study?
What role does FOXO3 play in aging?
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Academy
Mesenchymal Progenitor Cells
Definition and Origin: Mesenchymal progenitor cells (MPCs) are multipotent stem cells found in bone marrow, adipose tissue and other organs. They can differentiate into bone, cartilage and fat cells and play a critical role in tissue repair by secreting growth factors and immunomodulatory signals. Researchers harness their low immunogenicity and regenerative capacity to develop therapies for inflammatory and degenerative diseases.
FOXO3: The Longevity Gene
Role in Stress Resistance: FOXO3 is a transcription factor identified as a key regulator of longevity pathways in various organisms. It activates genes responsible for DNA repair, antioxidant defense and autophagy, helping cells cope with oxidative stress and DNA damage. Genetic variants of FOXO3 are associated with extended lifespan in human populations, making it an attractive target for anti-aging interventions.
Exosomes and Cellular Communication
Mechanism of Action: Exosomes are nano-sized vesicles released by cells that carry proteins, RNAs and microRNAs. They serve as messengers, influencing the behavior of recipient cells by transferring regulatory molecules. In engineered MPCs, exosomes become enriched with anti-inflammatory miRNAs and longevity-associated proteins, enabling them to modulate senescent cells and restore tissue homeostasis.
Gene Engineering for Rejuvenation
Engineering Process: By introducing FOXO3 into MPCs, scientists create senescence-resistant cells (SRCs) capable of enduring harsh aging environments. These cells withstand chronic inflammation and oxidative stress better than unmodified progenitors. When administered intravenously, SRCs home to damaged tissues and release rejuvenating exosomes, leading to functional improvements across multiple organs.
Implications for Aging Interventions
Translational Potential: Studies in aged primate models have shown that SRCs reverse cognitive decline, increase bone density and restore reproductive function without adverse effects. This proof of concept paves the way for clinical trials targeting human aging and age-related diseases. Future research will focus on optimizing cell delivery, scaling production and ensuring long-term safety.
