Elevated expression of mitochondrial cytochrome b and NADH dehydrogenase subunit 4/4L genes in senescent human cells.

In order to isolate cDNAs expressed differentially in senescent cells, we constructed a cDNA library from poly(A)+ RNA of senescent human fibroblast cells and screened cDNAs by the differential screening method. We isolated five cDNA clones expressed preferentially in the senescent cells. These five cDNA clones fell into two groups by cross-hybridization. Sequence analysis revealed that these cDNA clones were homologous to the human mitochondrial genes for cytochrome b (cytb) and NADH dehydrogenase subunit 4/4L (ND4/4L). Northern blot analysis demonstrated that the expression of these two mitochondrial genes were elevated in senescent cells compared to young cells. However, the expression of the mitochondrial cytochrome oxidase I gene was similar between young and senescent cells, implying that the preferential expression of the mitochondrial genes in the senescent cells was selective for cytb and ND4/4L genes. The results suggest that expressions of mitochondrial cytb and ND4/4L genes are regulated by a senescence-dependent mechanism.