T cell senescence: A novel therapeutic target for aging

Abstract

Aging of the immune system is characterized by a progressive loss of function, which limits vaccine effectiveness and is responsible for the increase in the susceptibility to infections, cancer and autoimmune diseases observed in elderly population. Recent evidences suggest that intrinsic alterations accumulated in T lymphocytes with age actively contribute to the state of chronic inflammation which underlies age-associated pathologies. We have accelerated the aging process in mice by inducing a mitochondrial dysfunction exclusively in T cells. These mice showed signs of systemic premature senescence and multimorbidity, evidencing that alterations in T cell functionality are sufficient to accelerate a whole-organism aging phenotype. Thus, T cell aging plays a crucial role in systemic deterioration and may be involved in neurodegenerative, cardiovascular and metabolic diseases whose incidence drastically increases with age. Understanding how the immune system contributes to age-associated multimorbidity is an urgent challenge, which could lead to the development of new therapeutic strategies destined to achieve a healthier aging. In this regard, immunotherapy is emerging as a new and promising technique aimed to delay age-associated diseases.