Cellular or replicative senescence is the phenomenon where normal differentiated diploid cells lose the ability to divide. This phenomenon is also known as the Hayflick phenomenon, while the limited division potential of normal cells is called the Hayflick limit. The entire period of serial passaging of cells in vitro is considered as cellular aging and begins with a long period of growth and cell proliferation. The end-stage of cellular aging is replicative senescence, involving processes that eventually lead to metabolic inactivation and cell death. Cellular aging is characterized by a stochastic accumulation of molecular damage in nucleic acids, proteins, and lipids causing a progressive failure of maintenance. Molecular damage is essentially recovered by the cell, however, damage accumulation occurs when a certain damage threshold is exceeded. The maintenance machinery consists of the multiple pathways of repair including nuclear and mitochondrial DNA repair, as well as pathways of protein turnover and repair. The main mechanistic hypotheses for explaining the accumulation of molecular damage and thus failure of maintenance are: altered gene regulation, somatic mutation accumulation, protein errors and modifications, and free radical-induced damage.
