T-Kininogen is a biomarker of senescence in rats

We have previously reported on the identification of T-kininogen (T-KG) as a gene whose expression is increased during senescence in male Sprague-Dawl ey (S-D) rats. Serum T-KG levels increase 2.5-4 months before the time of d eath for any given animal, irrespective of the actual age of the animal at the time of this event. Furthermore, dietary restriction (DR) delays, but d oes not prevent, the increase in serum T-KG levels. In the present study, w e have assessed whether or not the age-related increase in T-KG is a common feature of senescence in other strains of rat. We have analyzed hepatic T- KG mRNA levels in male Fischer 344 rats (F344), as well as in male and fema le (Fischer 344 x Brown Norway)F1 rats (F1). In both of these strains, we o bserved a dramatic increase in hepatic T-KG mRNA levels when male rats appr oach senescence. The mRNA levels behave similarly in F1 and S-D rats, in th at the increase occurs late in life, and it is either repressed or delayed by DR. In contrast, the increase in T-KG mRNA levels in F344 rats occurs ea rlier in life, and is not significantly affected by DR. Young female Fl rat s fed ad libitum (AL) show a statistically significant (P = 0.0009) 2.6-fol d higher level of T-KG mRNA, as compared to their male counterparts. Thus, while we still observe an age-related increase in this parameter in both AL and DR female F1 rats, the difference is statistically significant (P = 0. 0001) only in DR animals. We conclude that the increase in T-KG gene expres sion is a common feature of senescence and that, at least in males of these commonly used rat strains, T-KG can be used as a reliable biomarker of agi ng. Since the increase in T-KG gene expression does not appear to correlate with inflammatory processes, and since different strains of animals succum b to different pathologies, these results further suggest that the increase in T-KG expression might be related to the process of aging per se, rather than to any given age-related pathology. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.