BACKGROUND: The dramatic alterations in the appearance of the integument with increasing age are due in part to a progressive destruction of the delicate architecture of the connective tissue components of the dermis. Both collagenous and elastic components display a degeneration consistent with the overexpression of proteolytic activity. Recent advances in the field of molecular gerontology, using in vitro models of cellular aging, are yielding clues as to the fundamental causes of dermal aging. OBSERVATIONS: Dermal fibroblasts possess a finite replicative capacity of 50 to 100 doublings, then cease replicating in response to growth factors. Cells cultivated to the end of their replicative lifespan in vitro display alterations consistent with their playing a role in aging in vivo. In particular, senescent dermal fibroblasts overexpress metalloproteinase activities that may explain the age-related atrophy of extracellular matrix architecture. CONCLUSIONS: The recent discovery of a structural change in the telomeric region of the genome with cellular aging and new insights into DNA damage checkpoint mechanisms offer new opportunities to uncover both the molecular mechanisms regulating cellular aging and possibly to devise new strategies to manipulate these molecular events for therapeutic effect.
BACKGROUND: The dramatic alterations in the appearance of the integument with increasing age are due in part to a progressive destruction of the delicate architecture of the connective tissue components of the dermis. Both collagenous and elastic components display a degeneration consistent with the overexpression of proteolytic activity. Recent advances in the field of molecular gerontology, using in vitro models of cellular aging, are yielding clues as to the fundamental causes of dermal aging. OBSERVATIONS: Dermal fibroblasts possess a finite replicative capacity of 50 to 100 doublings, then cease replicating in response to growth factors. Cells cultivated to the end of their replicative lifespan in vitro display alterations consistent with their playing a role in aging in vivo. In particular, senescent dermal fibroblasts overexpress metalloproteinase activities that may explain the age-related atrophy of extracellular matrix architecture. CONCLUSIONS: The recent discovery of a structural change in the telomeric region of the genome with cellular aging and new insights into DNA damage checkpoint mechanisms offer new opportunities to uncover both the molecular mechanisms regulating cellular aging and possibly to devise new strategies to manipulate these molecular events for therapeutic effect.
Authors: Desiree Nguyen; Dru F Leistritz; Lesley Turner; David MacGregor; Kamal Ohson; Paul Dancey; George M Martin; Junko Oshima Journal: Biochem Biophys Res Commun Date: 2006-11-27 Impact factor: 3.575
Authors: M H Linskens; J Feng; W H Andrews; B E Enlow; S M Saati; L A Tonkin; W D Funk; B Villeponteau Journal: Nucleic Acids Res Date: 1995-08-25 Impact factor: 16.971
Authors: Steve Thomas Pannakal; Sibylle Jäger; Albert Duranton; Amit Tewari; Subarna Saha; Aneesha Radhakrishnan; Nita Roy; Jean François Kuntz; Soraya Fermas; Darryl James; Jane Mellor; Namita Misra; Lionel Breton Journal: PLoS One Date: 2017-07-20 Impact factor: 3.240