The Cellular Senescence Program

This chapter presents a broad account of factors that contribute to cellular senescence(definition) and how senescent cells in turn contribute to aging and age-associated pathologies of the lungs. Cellular senescence has a dual impact in maintaining tissue integrity and homeostasis. Under in vitro culture conditions, cellular senescence is classified as the replicative senescence and premature senescence, which correspond to the activation of DNA damage response signals and oxidative stress signals, respectively. The phenotypic alteration in senescent cells results in production of excessive growth factors, matrix metalloproteinases, cytoskeletal proteins, and inflammatory mediators, which are collectively known as senescence-associated secretory phenotype (SASP). SASP leads to increased inflammation and angiogenic potential within the microenvironment of the damaged tissue area. The chapter describes two classic mechanisms of senescence involving the tumor suppressor proteins p53 and p21 and p16 and pRB along with their respective downstream effector proteins.