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 meth od. We isolated five cDNA clones expressed preferentially in the senes cent cells. These five cDNA clones fell into two groups by cross-hybri dization. Sequence analysis revealed that these cDNA clones were homol ogous to the human mitochondrial genes for cytochrome b (cytb) and NAD H dehydrogenase subunit 4/4L (ND4/4L). Northern blot analysis demonstr ated that the expression of these two mitochondrial genes were elevate d in senescent cells compared to young cells. However, the expression of the mitochondrial cytochrome oxidase I gene was similar between you ng and senescent cells, implying that the preferential expression of t he mitochondrial genes in the senescent cells was selective for cytb a nd ND4/4L genes. The results suggest that expressions of mitochondrial cytb and ND4/4L genes are regulated by a senescence-dependent mechani sm. (C) 1995 Academic Press, Inc.