Age-dependent regulation of mammalian DNA synthesis and cell proliferation In vivo

Abstract

That progressive increases in the time required to initiate certain enzyme inductions in rat liver in vivo may be used as a biochemical parameter of ageing was reported previously. The present paper indicates that a second biochemical manifestation of mammalian senescence may be a modification in the regulation of DNA synthesis and cell division in vivo. Administration of isoproterenol to 2-month-old rats initiates a single, tissue-specific burst of DNA synthesis, mitosis and division of certain salivary gland cells. Upon administration of identical body weight dosages of isoproterenol to older rats, it is evident that: 1. the time required to initiate DNA synthesis increases progressively and is directly proportional to the chronological age of rats from 2 to at least 24 months; 2. the delayed onset of DNA synthesis may be accompanied by a decreased magnitude of response; and 3. the ability to stimulate cell division may be abolished. These impairments probably are not attributable to changes in either the transport or pool size of deoxynucleotide precursor or in the immediate binding of isoproterenol. It seems likely, therefore, that age-dependent changes in the metabolism of RNA, protein and/or isoproterenol are responsible.