Immune system rejuvenation—approaches and real achievements

Interest in the mechanisms of aging of the immune system has not faded over the past 100 years, and it is caused by the immune-mediated development of age-related pathology, including autoimmune organ damage, reduced vaccination efficiency, atherosclerosis, the development of cardiovascular pathology, etc. In contrast to many other organs and systems, the immune system aging begins at an early age and has more pronounced changes that lead to the development of secondary pathology, which significantly affects life expectancy. But an effective strategy to restore immune function has not been developed yet. During this time, the mechanisms of age-related dysfunction of organs and cells of both the adaptive and innate immune systems were studied in detail—thymus involution, a decrease in the potential of hematopoietic stem cells, impaired differentiation and functions of immunocompetent cells, as well as the ways of their interaction. Numerous potential therapeutic targets have been identified and various approaches have been used to implement such therapeutic interventions. The review is devoted to replacement therapy using transplantation of hematopoietic stem cells (HSCs) and young lymphoid cells and tissues, cellular and systemic factor exchange in heterochronic parabiosis, and some other widely used life extension approaches. It has been proven that cell therapy using young cells to rejuvenate the old immune system, unfortunately, often turns out to be ineffective because it does not eliminate the root cause of age-related changes. The phenomenon of inflamm-aging that develops with age can significantly affect both the aging of the organism in general and the functioning of immunocompetent cells in particular. Therefore, the most promising direction in the restoration of immune functions during aging is systemic approaches that have a complex effect on the organism as a whole and can slow down the aging process.