Immunosenescence is Complex and May Include Some Beneficial Adaptations

Researchers here make the point that the aging of the immune system into a lesser capacity to defend against pathogens and senescent and potentially cancerous cells, the state known as immunosenescence, is both complex in its myriad changes, and probably includes some beneficial adaptations that help to modestly reduce the negative impact of aging. That is interesting to note, in those details that are known and hypothesized, but it doesn't really change the primary strategy for immune rejuvenation: restore active thymic tissue to enable production of new T cells; repair the hematopoietic stem cell populations and their niches to ensure creation of immune cells; clear out malfunctioning, senescent, and exhausted populations of immune cell.

For a long time, immunosenescence has been considered harmful. However, it is noteworthy that immunosenescence is a remodeling and retuning process with increase in some new functions rather than complete decline of immune function. Serum levels of IgG and IgA are increased with age, which is conducive to protecting against viral and bacterial infections effectively in older people. Although the generation of naive T cells and naive B cells continues to decline, the adaptive immune system adjusts to age-related changes and protects the body from most pathogens. Only later in life does the immune function decline gradually, which increases morbidity and mortality in the elderly.

But not all older people suffer from age-related diseases, centenarians can delay the aging process and live up to the limits of human life. Centenarians have a large quantity of anti-inflammatory molecules, such as TGF-β1, IL-10 and IL-1 receptor antagonist (IL-1RA), to counterbalance increased inflammatory molecules, such as IL-1β, IL-6, TNF-α, IL-8, C-reactive protein (CRP) and CXCL9, achieving a dynamic balance between pro-inflammatory and anti-inflammatory levels. In addition, telomere length and telomerase activity are higher in centenarians.

There are currently several strategies to deal with senescence and senescent cells. First of all, rejuvenation of old hematopoietic stem cells (HSCs) may be an effective therapeutic strategy to restore the balance between myeloid and lymphatic systems and the numbers of T and B cells. The involution of the thymus is one of the main features of aging, which might lead to the decrease of T cells, so restoring the structure and function of the aging thymus could reverse immunosenescence. Thymo-stimulatory property of IL-10, leptin, keratinocyte growth factor (KGF) and thymic stromal lymphopoietin (TSLP) may contribute to immune reconstitution of the elderly. IL-7 is a crucial cytokine for T cell development, so IL-7 treatment promotes the expansion of peripheral T cells and the diversity of T cell receptors. Telomerase is a significant component for T cell development, so upregulation of telomerase expression enhances T cell immune response and prolongs lifespan.



I still think that a completely off the shelf immune system is within the realm of possibility.

I mean what are allogeneic t cell treatments?

I guess why this is not possible is because there are just too many immune cell niches?

Then again treatments for MS routinely "wipe out" the immune system to reboot it.

Posted by: matt at September 13th, 2022 8:06 AM
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