Intrauterine programming of ageing.
Ageing is an unavoidable corollary to being alive; the most intuitive interpretation of ageing being that it is the consequence of progressive body degeneration. In agreement with this, current models propose that ageing occurs through a stepwise accumulation of DNA damage, which ultimately limits the regenerative capacity of tissues. On the other hand, there is increasing evidence that fetal distress can influence the development of disease in adult life, a phenomenon known as 'intrauterine programming'. The extent to which an intrauterine exposure to DNA damage can compromise lifespan remains unclear. My group has recently generated a murine model of a human syndrome linked to defective DNA repair and observed that these animals age prematurely, but the accumulation of DNA damage is restricted mostly to the embryonic period. Here, I discuss the implications of this finding and propose that ageing can be influenced by fetal distress.
Fernandez-Capetillo
Oscar
O
Genomic Instability Group, Spanish National Cancer Research Centre, Calle Melchor Fernandez Almagro 3, E-28029 Madrid, Spain. ofernandez@cnio.es
D000328:Adult; D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005260:Female; D005316:Fetal Distress / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000503:physiopathology