Senescent cells can in principle be distinguished by cell surface markers, and the immune system has evolved to detect and destroy these cells, yet senescent cells accumulate in later life. This is essentially the same situation as for cancerous cells, and thus much the same development process as already exists in the cancer research community could be undertaken to develop immunotherapies, including vaccines, that target senescent cells. The one big difference is that senescent cells sometimes serve useful purposes when present for the short-term, such as helping to coordinate regeneration from injury. This isn't a problem when we consider small molecule drugs that stress senescent cells in order to kill them, as those drugs are only present in the body for a short period of time. A highly efficient vaccine against senescent cells would be a lasting change to the dynamics of clearance, however, and could have some negative effects in addition to the broad benefits it would bring to older individuals.
A number of studies have shown that aging of the body is accompanied by the accumulation of senescent cells in various tissues and organs. This leads to tissue homeostasis and functional disorders typical of old age. Senescent cells typically express some age-related markers (such as p16INK4A, p21CIP1, etc.), have increased senescence-associated β-galactosidase (SA-β-Gal) activity, produce a number of cytokines and pro-inflammatory substances (the Senescence-Associated Secretory Phenotype, SASP), and have various defects in the protein quality control machinery. The physiological features of senescent cells affect their antigen profiles.
It is worth noting that senescent cells play an important role in some physiological processes. Thus, SASP factors are involved in tissue remodeling in early ontogenesis, as well as in repair and regeneration processes at later stages of development. In addition, cell cycle arrest, which is the most important feature of senescence, prevents possible malignancy. Senescent cells are normally present in tissues in limited numbers. However, the accumulation of these cells during the aging process is associated with the dysfunction of various tissues and organs, and the cumulative effect of SASP production contributes to chronic age-related inflammation, which increases the risk of developing age-related diseases.
Despite the promising results of using some drugs aimed at killing senescent cells (senolytics) or reducing the negative effects of SASP (senomorphics), the existing pharmacological approaches still do not possess the high specificity toward senescent cells, do not take into account their diversity, and are associated with the risk of side effects. In this context, a promising alternative is the development of methods for targeted elimination of senescent cells with the help of adaptive immunity mechanisms. Various attempts to create senolytic vaccines that remove senescent cells from specific tissues have already been made.
However, the development of such vaccines is associated with certain problems. Unique Senescent-Specific Antigens (SSAs) absent in normal cells are still unknown, which hinders the development of safe senolytic vaccines due to the risk of damage to the healthy tissues. The high antigenic diversity of senescent cells, both at individual and population levels, significantly complicates the search for target antigens for the creation of universal senolytic vaccines. Obviously, tolerance to senescence-associated antigens is a serious problem. Since senescent cells are the body's own cells, the mechanisms of central and peripheral tolerance can act toward the antigens they express. Thus, overcoming tolerance to senescence-associated antigens is one of the key challenges in the development of senolytic vaccines.
Link: https://doi.org/10.3390/vaccines12121389
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