The immune system becomes unruly and ineffective in old age: on the one hand it generates ever greater levels of harmful chronic inflammation, while on the other it no longer has a sufficient population of effective cells able to tackle new threats, scan for cancerous cells, and eliminate senescent cells from the body. It becomes overactive and underachieving, and a sizable portion of the more obvious aspects of age-related frailty stem from the lack of a robust immune response.
Why does this happen? No doubt the normal culprits leave their mark: the forms of accumulated cellular and molecular damage that degrade tissues and cell populations, including those involved in generating and maintaining immune cells. Beyond this, however, there are problems that inevitably arise due to the evolved structure of the immune system: it has what are in effect built-in limits. The first is a limit to the number of immune cells that can be supported at any one time, as the potential supply of new cells diminishes to a trickle quite early in adulthood, as an organ necessary for their creation - the thymus - atrophies. The second limit of interest stems from the fact that the adaptive immune system devotes cells to remembering threats, and thanks to persistent threats like herpesviruses, ever more of the available cell population is devoted to memory rather than action. So the end result is an evolved system that is front-loaded for early success, but which systematically falls apart much later.
What can be done about this? Destroying unwanted and duplicative memory cells looks promising, as that will trigger replacement with fresh cells capable of action. Increasing control over stem cells offers the possibility of periodic infusions of large numbers of immune cells generated from a recipient's own cells. This would surmount the natural immune capacity at the upper end. Another approach that might achieve the same result is to restore the thymus, and thus restore a youthful flow of new immune cells. This would use the approaches of tissue engineering and regenerative medicine to either build a new thymus for transplantation, or regrow the existing thymus in situ.
The SENS Research Foundation has been putting a modest amount of funding into spurring greater progress towards thymic regeneration, and this year one of the young researchers in the undergraduate program will be working on this project, established in partnership with the Wake Forest Institute for Regeneration Medicine:
My early research experience investigating how age affects regeneration is what sparked my interest in the SENS Research Foundation (SRF). I wanted to be able to learn and see new techniques that are being used to try to help slow down or reverse the process of aging.
As an undergraduate student, I have had the honor of continuing to explore my research interests working at the Wake Forest Institute for Regenerative Medicine (WFIRM) under the mentorship of Dr. James Yoo on the skin bioprinting project - a project designed to create safer and scar-less treatments for people in need of skin grafts. Successful Dr. John Jackson. The thymus is the primary lymphoid organ for the production of T cells. It is comprised of two compartments, the cortex and the medulla. The T cells undergo maturation in the cortex section of the thymus and positive selection for a functional T cell receptor. The medulla is important for the negative selection of T cells to eliminate self-reactive T-cells and is also the region where mature T cells exit from the thymus.
As we age, the thymus decreases in immune function. This leads to a shift toward a greater and greater proportion of memory T cells compared to naïve T cells. In order to reverse this effect and enhance immune response, there is a need to regenerate thymus tissue and increase naïve T cell population. This project aims to regenerate the thymus using natural thymus scaffolds which have been reseeded with cells.