Age-dependent down-regulation of DNA polymerase δ1 in human lymphocytes.

ABSTRACT

Aging progress and degeneracy of functional activity are mainly attributed to the decreased DNA repair potential. DNA polymerase (pol) δ activity plays an essential role in genome stability by virtue of its crucial DNA replication and repair capacity. To order to clarify the role of DNA pol δ in aging progression, we firstly examined the expressions of its catalytic subunit named DNA pol δ1 in human lymphocytes at different age stages, respectively, and then observed the effect of diseases on DNA pol δ1 in vivo and of nutriture on its expressions in 2BS cells in vitro. Blood samples from the healthy subjects and patients with diabetes mellitus and coronary heart disease were collected, respectively, for analysis of transcription and protein expressions of DNA pol δ1 by RT-PCR and western blot. 2BS cells of PD30 and PD47 were incubated in both normal medium and other mediums of different nutritures for verifying the differential expressions of DNA pol δ1. Results showed that the mRNA expression of DNA pol δ1 decreased substantially with age and the protein levels were well consistent with gene levels. Furthermore, there were no significant differences in DNA pol δ1 expressions between the groups of healthy individuals and the age matched patients. In addition, DNA pol δ1 gene expression levels were not affected by nutritional status in vitro. Our findings collectively confirmed that the down-regulations of DNA pol δ1 are age-related and have little bearing on diseases and nutritures. DNA pol δ1 has great potential for a new biomarker of aging.