Histone variants, H1subtypes and other chromatin proteins as biomarkers of age and caloric restriction in rats

Abstract

The synthesis and phosphorylation levels of basic chromatin proteins from cell cycle phases of dividing bone marrow cells in Fischer 344 rats were investigated by gel electrophoresis. Two groups of rats, young ad libitum (Y/A 3 mo.) and old ad libitum (O/AL 28 mo.), had free access to rat chow, and a third group of old rats was maintained on a calorie-restricted intake (O/CR 28 mo.). Histone H1 subtypes a, b and c from combined S+G2 phase revealed highest amounts of [3H] lysine incorporation in Y/AL, lowest in O/AL, and intermediate levels in O/CR animals, while subtypes e and I° were highest in O/AL, lowest in Y/AL, and mid level in O/CR. The 32p-orthophosphate incorporation of these subtypes followed a parallel scenario as with lysine. Histone H4 variants from S phase demonstrated the highest levels of lysine labeling in O/AL, lowest in Y/AL and intermediate levels in O/CR. The H1 variants were similar in synthesis patterns to H4 variants but less dramatic. Minor histone variants M2, M3 and M4 manifested most synthesis in O/AL, least in Y/AL and mid levels in O/CR. Conversely, M1 synthesis was high in Y/AL, low in O/AL and modest in O/CR. Ubiquitin followed a similar pattern in lysine labeling to M1 and A24 which was inversely proportional to ubiquitin. The metabolic activity of these basic proteins in O/CR exemplifies a condition characteristic of Y/AL animals modulated by age and diet dependent factors.