Base excision repair, aging and health span.
DNA damage and mutagenesis are suggested to contribute to aging through their ability to mediate cellular dysfunction. The base excision repair (BER) pathway ameliorates a large number of DNA lesions that arise spontaneously. Many of these lesions are reported to increase with age. Oxidized guanine, repaired largely via base excision repair, is particularly well studied and shown to increase with age. Spontaneous mutant frequencies also increase with age which suggests that mutagenesis may contribute to aging. It is widely accepted that genetic instability contributes to age-related occurrences of cancer and potentially other age-related pathologies. BER activity decreases with age in multiple tissues. The specific BER protein that appears to limit activity varies among tissues. DNA polymerase-beta is reduced in brain from aged mice and rats while AP endonuclease is reduced in spermatogenic cells obtained from old mice. The differences in proteins that appear to limit BER activity among tissues may represent true tissue-specific differences in activity or may be due to differences in techniques, environmental conditions or other unidentified differences among the experimental approaches. Much remains to be addressed concerning the potential role of BER in aging and age-related health span.
Xu
Guogang
G
Department of Cellular & Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Herzig
Maryanne
M
Rotrekl
Vladimir
V
Walter
Christi A
CA
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics; D011110:Polymorphism, Genetic; D051381:Rats; D013091:Spermatogenesis
D045643:DNA Repair Enzymes