Ageing, differentiation, and gene expression in rat epididymal preadipocytes.

Ageing results in decreased replicative potential of preadipocytes, as well as reduced capacities for the lipid accumulation and increases in lipogenic enzyme activities during differentiation of preadipocytes into fat cells. To determine whether decreased differentiation is associated with decreased levels of mRNA for differentiation-dependent genes and whether early as well as late components of the differentiation programme are affected by ageing, we measured beta-actin, alpha-tubulin, lipoprotein lipase, and glycerol-3-phosphate dehydrogenase mRNA levels in undifferentiated and differentiated epididymal preadipocytes from 3-, 17-, and 24-month-old Fischer 344 rats. During ageing, diminished differentiation-related changes occurred in mRNAs affected early (actin, tubulin), midway through (lipoprotein lipase), and late (glycerol-3-phosphate dehydrogenase) in the preadipocyte differentiation process. Hence, early as well as late phases of the differentiation programme were affected by ageing. The effects involved changes in gene transcription or mRNA processing. Our results were not consistent with the hypothesis that age-related decreases in replication are caused by an increased tendency for cell differentiation.