text: Because mechanisms that control the accumulation of damage through the lifetime of a cell are essential to longevity, it is logical that caretaker and gatekeeper genes play a significant role in cellular aging.  Increased activity of caretaker genes postpones aging, increasing lifespan.  This is because of the regulatory function associated with caretaker genes in maintaining the stability of the genome.  The actions of caretaker genes contribute to increasing lifespan of the cell.
  A specific purpose of caretaker genes has been outlined in chromosomal duplication. Caretakers have been identified as crucial to encoding products that maintain the telomeres. It is believed that degradation of telomeres, the ends of chromosomes, through repeated cell cycle divisions, is a main component of cellular aging and death.
  It has been suggested that gatekeeper genes confer beneficial anti-cancer affects but may provide deleterious effects that increase aging. This is because young organisms experiencing times of rapid growth necessitate significant anti-cancer mechanisms.  As the organism ages, however, these formerly beneficial pathways become deleterious by inducing apoptosis in cells of renewable tissues, causing degeneration of the structure.  Studies have shown an increased expression of pro-apoptotic genes in age-related pathologies.  This is because the products of gatekeeper genes are directly involved in coding for cellular growth and proliferation.
  However, dysfunctional caretaker genes do not always lead to a cancerous phenotype.  For example, defects in nucleotide excision repair pathways are associated with premature aging phenotypes in diseases such as Xeroderma pigmentosum and Trichothiodystrophy.  These patients exhibit brittle hair, nails, scaly skin, and hearing loss – characteristics associated with simple human aging.  This is important because the nucleotide excision repair pathway is a mechanism thought to be encoded by a caretaker gene.  Geneticists studying these premature-aging syndromes propose that caretaker genes that determine cell fate also play a significant role in aging.  Accumulation of DNA damage with age may be especially prevalent in the central nervous system because of low DNA repair capability in postmitotic brain tissue.
  Similarly, gatekeeper genes have been identified as having a role in aging disorders that exhibit mutations in such genes without an increased susceptibility to cancer.  Experiments with mice that have increased gatekeeper function in the p53 gene show reduced cancer incidence (due to the protective activities of products encoded by p53) but a faster rate of aging.
  Cellular senescence, also encoded by a gatekeeper gene, is arrest of the cell cycle in the G1 phase.  Qualitative differences have been found between senescent cells and normal cells, including differential expression of cytokines and other factors associated with inflammation.  It is believed that this may contribute, in part, to cellular aging.
  In sum, although mechanisms encoded by gatekeeper and caretaker genes to protect individuals from cancer early in life, namely induction of apoptosis or senescence, later in life these functions may promote the aging phenotype.