mRNA level of alpha-2-macroglobulin as an aging biomarker of human fibroblasts in culture.

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 (alpha(2)M) 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 alpha(2)M showed a positive linear-correlation with cumulative PDL. Additional assays revealed that the levels of alpha(2)M increased in irreversible growth arrest induced by sublethal H(2)O(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 alpha(2)M can be used as a biomarker of aging in cultured fibroblasts. mRNA level of alpha(2)M showed significant difference between newborn and old human leucocytes, which suggest that the mRNA level of alpha(2)M may be used as a biomarker of aging in vivo.