LAUSR

Simple Summary Aging is a progressive decline of an organism over time. In contrast, senescence occurs throughout an organism’s lifespan. It is a cell-cycle arrest preventing the proliferation of damaged cells. Cellular and molecular senescence timing is crucial for the pace of aging and disease development and progression. The accumulation of senescent cells during a lifespan leads to organismal senescence. Senescent multinucleated giant cells are present in many age-related diseases and cancer. Although senescence was assumed to be irreversible, studies now show that senescent multinucleated giant cells overcome senescence in various cancers, becoming the source of highly aggressive mononucleated stem-like cells, which divide and initiate tumor development and progression. Abstract This review introduces the subject of senescence, aging, and the formation of senescent multinucleated giant cells. We define senescence and aging and describe how molecular and cellular senescence leads to organismal senescence. We review the latest information on senescent cells’ cellular and molecular phenotypes. We describe molecular and cellular features of aging and senescence and the role of multinucleated giant cells in aging-related conditions and cancer. We explain how multinucleated giant cells form and their role in aging arteries and gonads. We also describe how multinucleated giant cells and the reversibility of senescence initiate cancer and lead to cancer progression and metastasis. We also describe molecules and pathways regulating aging and senescence in model systems and their applicability to clinical therapies in age-related diseases.