Targeting cellular senescence: A promising approach in respiratory diseases

Geriatr Gerontol Int. 2024 Mar:24 Suppl 1:60-66. doi: 10.1111/ggi.14653. Epub 2023 Aug 21.

Abstract

Cellular senescence serves as a significant tumor suppression mechanism in mammals. Cellular senescence is induced in response to various stressors and acts as a safeguard against the uncontrolled proliferation of damaged cells that could lead to malignant transformation. Senescent cells also exhibit a distinctive feature known as the senescence-associated secretory phenotype (SASP), wherein they secrete a range of bioactive molecules, including pro-inflammatory cytokines, growth factors, and proteases. These SASP components have both local and systemic effects, influencing the surrounding microenvironment and distant tissues, and have been implicated in the processes of tissue aging and the development of chronic diseases. Recent studies utilizing senolysis models have shed light on the potential therapeutic implications of targeting senescent cells. The targeting of senescent cell may alleviate the detrimental effects associated with cellular senescence and its SASP components. Senolytics have shown promise in preclinical studies for treating age-related pathologies and chronic diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Respiratory diseases have emerged as a significant global health concern, responsible for a considerable number of deaths worldwide. Extensive research conducted in both human subjects and animal models has demonstrated the involvement of cellular senescence in the pathogenesis of respiratory diseases. Chronic pulmonary conditions such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis have been linked to the accumulation of senescent cells. This review aims to present the findings from research on respiratory diseases that have utilized systems targeting senescent cells and to identify potential therapeutic strategies for the clinical management of these conditions. Geriatr Gerontol Int 2024; 24: 60-66.

Keywords: COPD; COVID‐19; IPF; cancer; cellular senescence.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Cellular Senescence / physiology
  • Humans
  • Lung
  • Mammals
  • Neoplasms* / drug therapy
  • Pulmonary Disease, Chronic Obstructive*
  • Tumor Microenvironment