Age‐associated alterations in murine dermis through inflammatory response with mitochondrial DNA deletions.

Kawaguchi, Koichiro; Kim, Sang‐Eun; Sugiyama, Daijiro; Sugimoto, Masataka; Maruyama, Mitsuo

Aim: Skin aging is caused by intrinsic and extrinsic mechanisms. Because it is difficult to distinguish intrinsic mechanisms from extrinsic skin aging, the mechanisms of intrinsic skin aging remain unclear. The present study aimed to characterize age‐associated alterations in murine skin and investigate the mechanisms of intrinsic skin aging. Methods: We measured morphological changes in dorsal skin from young (aged 2 months) and old (aged 22–24 months) mice by histological analysis. Age‐associated alteration of gene expression patterns was determined by quantitative polymerase chain reaction and immunohistochemistry. Reactive oxygen species production in mouse dorsal skin was detected by confocal laser scanning microscopy. Mitochondrial DNA deletions were detected by conventional polymerase chain reaction and quantitative polymerase chain reaction analyses. Results: Chronologically aged skin had dermal atrophy caused by increased matrix‐degrading enzymes and decreased collagen synthesis. Chronologically aged skin samples also had increased senescence‐associated secretory phenotype factors, elevated reactive oxygen species production and a higher frequency of the mitochondrial DNA common deletion. Conclusions: These observations suggest that chronological skin aging is associated with increased frequency of the mitochondrial DNA common deletion and chronic inflammation through the reactive oxygen species–senescence‐associated secretory phenotype axis. Geriatr Gerontol Int 2019; 19: 451–457.

SKIN diseases; REACTIVE oxygen species; ANIMAL experimentation; COLLAGEN; DNA; GENE expression; HISTOLOGICAL techniques; IMMUNOHISTOCHEMISTRY; INFLAMMATION; MICE; MICROSCOPY; MITOCHONDRIA; GENETIC mutation; POLYMERASE chain reaction; SKIN aging; PHENOTYPES; ATROPHY; MATRIX metalloproteinases; METABOLISM; DISEASE risk factors

Geriatrics & Gerontology International, 2019, Vol 19, Issue 5, p451

1444-1586

Academic Journal

10.1111/ggi.13635