Recent Advancement in Elimination Strategies and Potential Rejuvenation Targets of Senescence.

Abstract

Cellular senescence is a state of exiting the cell cycle, resisting apoptosis, and changing phenotype. Senescent cells (SCs) can be identified by large, distorted morphology and irreversible inability to replicate. In early development, senescence has beneficial roles like tissue patterning and wound healing, where SCs are cleared by the immune system. However, there is a steep rise in SC number as organisms age. The issue with SC accumulation stems from the loss of cellular function, alterations of the microenvironment, and secretions of pro-inflammatory molecules, consisting of cytokines, chemokines, matrix metalloproteinases (MMPs), interleukins, and extracellular matrix (ECM)-associated molecules. This secreted cocktail is referred to as the senescence-associated secretory phenotype (SASP), a hallmark of cellular senescence. The SASP promotes inflammation and displays a bystander effect where paracrine signaling turns proliferating cells into senescent states. To alleviate age-associated diseases, researchers have developed novel methods and techniques to selectively eliminate SCs in aged individuals. Although studies demonstrated that selectively killing SCs improves age-related disorders, there are drawbacks to SC removal. Considering favorable aspects of senescence in the body, this paper reviews recent advancements in elimination strategies and potential rejuvenation targets of senescence to bring researchers in the field up to date.