Abstract
Cellular senescence is a well-established model system for studying the molecular basis of aging. To identify a reliable biomarker for cellular age and further study the gene expression of aging, we profiled the gene expression difference between aged and young cultured human embryonic lung fibroblasts by high-density complementary deoxyribonucleic acid (cDNA) arrays. Among the differentially expressed genes, alpha-2-macroglobulin (α 2M) was selected for further study. Its gene expression level as a function of population doubling level (PDL) in cultured fibroblasts was determined by RT-PCR and northern hybridization. mRNA level of α 2M showed a positive linear-correlation with cumulative PDL. Additional assays revealed that the levels of α 2M increased in irreversible growth arrest induced by sublethal H 2O 2, but not in quiescent state of cultured fibroblasts induced by serum-deprivation, and remained stable in Hela cells. These results suggest that mRNA level of α 2M can be used as a biomarker of aging in cultured fibroblasts. mRNA level of α 2M showed significant difference between newborn and old human leucocytes, which suggest that the mRNA level of α 2M may be used as a biomarker of aging in vivo.
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