CELLULAR AND MOLECULAR BIOMARKERS INDICATE PRECOCIOUS IN-VITRO SENESCENCE IN FIBROBLASTS FROM SAMP6 MICE - EVIDENCE SUPPORTING A MURINE MODEL OF PREMATURE SENESCENCE AND OSTEOPENIA

A variety of short-lived mouse strains (SAMP strains) and control stra ins of less abbreviated life span (SAMR strains) have been proposed as murine models of accelerated senescence. Each SAMP strain, in additio n to displaying ''progeroid'' traits of accelerated aging, exhibits a singular age-related pathology. The application of this animal model t o the study of normal aging processes has been and remains controversi al. Therefore, toe have undertaken a study of dermal fibroblasts deriv ed from the short-lived SAMP6 strain, which shows early-onset and prog ressive osteopenia. We have investigated cellular and molecular charac teristics that are associated,vith in vitro aging of normal human fibr oblasts, and which are exacerbated in fibroblasts from patients with W erner syndrome, a human model of premature senescence. We found that S AMP6 dermal fibroblasts, relative to SAMR1 and C57BL/6 controls, exhib it characteristics of premature or accelerated cellular senescence wit h regard to in vitro life span, initial growth rate, and patterns of g ene expression.