page_title: Senescence
section_title: Cellular senescence
hierarchical_section_title: Senescence / Cellular senescence
caption_attribution_description: Microscopic image of senescence on mouse embryonic fibroblast cells. (SABG assay. 100-fold magnification.). (upper) Before senescence, at 2nd (early) passage. Note that MEFs were spindle shaped. (lower) After senescence, at 8th (late) passage. MEFs grew larger and flatten. Blue-green areas indicate the expression of senescene-associated beta-galactosidase.
context_page_description: Senescence or biological aging is the gradual deterioration of functional characteristics. The word senescence can refer either to cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle.
  Senescence is the inevitable fate of all multicellular organisms with germ-soma separation, but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as Hydra, have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.
  Environmental factors may affect aging, for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates. Two organisms of the same species can also age at different rates, making biological aging and chronological aging distinct concepts.
context_section_description: Cells accumulate damage over time. In particular DNA damage, e.g. due to reactive oxygen species, leads to the accumulation of harmful somatic mutations.
  The cellular senescence theory of aging posits that organismal aging is a consequence of the accumulation of less physiologically useful, i.e. senescent cells. In agreement with this, the experimental elimination of senescent cells from transgenic progeroid mice and non-progeroid, naturally-aged mice led to greater resistance against aging-associated diseases. Ectopic expression of the embryonic transcription factor, NANOG, is shown to reverse senescence and restore the proliferation and differentiation potential of senescent stem cells.
  In many organisms, there is asymmetric cell division, e.g. a stem cell dividing to produce one stem cell and one non-stem cell. The cellular debris that cells accumulate is not evenly divided between the new cells when they divide. Instead more of the damage is passed to one of the cells, leaving the other cell rejuvenated. One lineage then undergoes cellular senescence faster than the other.
  Natural selection can remove damaged cells and prevent their proliferation, counterbalancing the natural tendency for damaged cells to accumulate. However, some cells mutate in ways that escape these control mechanisms. Cancer cells avoid replicative senescence to become immortal. In about 85% of tumors, this evasion of cellular senescence is the result of up-activation of their telomerase genes.
  In most multicellular species, somatic cells eventually experience replicative senescence and are unable to divide. This can prevent highly mutated cells from becoming cancerous. In culture, fibroblasts can reach a maximum of 50 cell divisions; this maximum is known as the Hayflick limit. Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length.
caption: Cellular senescence
  (upper) Primary mouse embryonic fibroblast cells (MEFs) before senescence. Spindle-shaped. (lower) MEFs became senescent after passages. Cells grow larger, flatten shape and expressed senescence-associated β-galactosidase (SABG, blue areas), a marker of cellular senescence.
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