Towards a biomarker of mammalian senescence: carbonic anhydrase III

Three proteins (D2, D3, D4) have been identified in the male Fischer 344 rat liver that decrease their concentration dramatically to virtually zero during the transition from physiological maturity to senescence. D3 (Mr 28 kDa), absent (or at a very low concentration) from the livers of newborns and females of all ages, reaches at 60 days (sexual maturity) its maximum concentration, which declines almost linearly thereafter. A homologous protein (CNBr peptide map) occurs in the BALB/c mouse under similar conditions. D3 was purified and since its N-terminal is blocked, digested with CNBr. SDS-PAGE-separated peptides were blotted upon Immobilon and sequenced. The partial sequence matches that of rat carbonic anhydrase III. Treatment of senescent rats with 5 alpha-dihydrotestosterone restores D4 completely, yet D2 and D3 only partially, towards their maximum life-time concentration. Thus senescence-related factors (e.g. hepatic androgen receptor) aside from serum testosterone are responsible for the disappearance of the three proteins from the senescent liver.