Regenerate the thymus gland
One step closer to restoring the thymus
A Step Closer to Regenerating the Aging Thymus
Steve Hill, Life Extension Advocacy Foundation
Translated by Ariel Finerman, Habr
Scientists from the Monash Biomedicine Institute have made progress in rejuvenating the aging immune system by identifying the factors responsible for thymus reduction.
The thymus decreases as we age
The thymus is one of the most important organs in the body, and it is in it that thymocytes formed in the bone marrow become new T cells before maturing in the lymph nodes to become defenders of the adaptive immune system. However, as we get older, the thymus is increasingly replaced by fat and begins to shrink, and its ability to produce new T cells decreases dramatically. This process is known as thymus involution and actually begins shortly after puberty, so this is one aspect of aging that begins very early, although it takes many decades before its reduction causes serious problems.
A decrease in the production of new T cells from the thymus leads to a decrease in the adaptive immune system and is part of the overall aging of the immune system. The end result of the immunosenescence process is that your body can no longer provide effective protection against diseases, is activated incorrectly, which leads to immune dysfunction and chronic inflammation.
A decrease in the thymus is associated with the risk of developing cancer, which increases dramatically with age, according to the concept of immunosenescent cancer. Immune aging is also strongly correlated with multiple age-related pathologies, which is probably not surprising, given that the elderly immune system can no longer respond effectively and adequately to the invasion of pathogenic microorganisms. Although it has long been known that the thymus decreases with age, the exact mechanisms of this involution have not been completely clear.
Downward spiral
The new work has shed light on what leads to loss of thymus function in old age and, as a result, to disruption of immune cell production. Published in the journal Cell Reports, a new study has laid the foundation for the development of treatments that can help the thymus restore its ability to produce T cells and fight infections and diseases.
Researchers show that BMP4 and activin are growth and differentiation factors that are key in the self-renewal and differentiation of thymus epithelial stem cells, and that changes in their levels as a result of aging cause the loss of these epithelial cells. This loss as a result leads to a decrease in the production of T cells in the thymus, which ultimately leaves us open to infection and disease. This study is the first in the world, and reveals the main reason why we experience the loss of thymus epithelial stem cells, as well as the molecules and mechanisms that control this process.
Figure from the article Lepletier et al., Interplay between Follistatin, Activin A, and BMP4 Signaling Regulates Postnatal Thymic Epithelial Progenitor Cell Differentiation during Aging – VM
The scientists' next step will be to find ways to reverse this decrease and turn the thymus back on to resume T-cell production. Scientists believe that age-related changes in the thymus can be reversed, and now they are studying whether it is possible to design a therapy for the regeneration of thymus epithelial stem cells.
A key feature of immune disorders with age is the progressive involution of thymus tissue responsible for the production of naive T cells. In this study, we described two main phases of thymus epithelial cell (TEC) loss during aging: blocking the differentiation of mature TEC from the pool of immature progenitors, occurring at the beginning of puberty, followed by disruption of bi-potent differentiation of TEC progenitors and depletion of Sca-1lo cTEC and mTEC pools of specific progenitors. We found that an increase in follistatin production contributes to their death. The loss of TEC occurs mainly due to the antagonism of activin A signaling, which, as we show, is necessary for TEC maturation and acts in dissonance with BMP4, which contributes to the preservation of TEC precursor pools. These results confirm that the imbalance of activin A and BMP4 signaling underlies the degeneration of postnatal TEC pools during aging, and its reversal allows to temporarily increase the pools of mature TEC.
Conclusion
Effective targeting of these pathways can lead to the restoration of not only the production of T cells by the thymus, but also the diversity of T cells. This can significantly improve the health of elderly people, who usually have poor or almost non-functional T-cell production as a result of thymus involution. If it is possible to develop a therapy that restores the thymus, restoring its functions to a younger level, it can improve the health of older people and reduce the risk of a variety of age-related pathologies and infectious diseases.
Some companies and research groups are currently engaged in thymus rejuvenation, and the available information, including animal experiments and preliminary human trials, allow us to believe that thymus regeneration is quite possible in the near future.
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