MITOCHONDRIAL-DNA DELETIONS IN HUMAN SKIN REFLECT PHOTO RATHER THAN CHRONOLOGICAL AGING

We have examined the use of mitochondrial DNA (mtDNA) as a molecular m arker to study the relation between chronologic aging and photoageing in human skin. Using a 3-primer quantitative polymerase chain reaction method we have studied changes in the ratio of the 4977 bp deleted to wild-type mtDNA in relation to sun exposure and chronologic age of hu man skin, Based on previous studies, samples showing greater than 1% d eleted mtDNA were classed as abnormal. There was a significant increas e in the incidence of high levels (i.e., >1%) of the 4977 bp deleted m tDNA in sun-exposed sites (27%, 27 of 100) compared with sun-protected sites (1.1%, one of 90) (Fisher's exact test, p < 0.0001), There appe ared to be no relation between the frequency of the mtDNA deletion and age, Analysis of split skin samples showed that most deletions (93%, n = 27) were confined to the dermal rather than the epidermal componen t, and in keeping with this deletions were found in three of six prima ry cultures of fibroblasts from sun-exposed sites, Deletions were not seen in the epidermal component of several epidermal tumors nor were d eletions seen in fibroblasts cultured from an individual with Werner's syndrome, We propose that deletions or mutations of mitochondrial DNA may be useful as a marker of cumulative ultraviolet radiation exposur e.