SIRT1, IGFBP-3 and CAV1 Promoter DNA Methylation in Aging

Abstract

The human genome is a fragile and highly conserved structure that accumulates a wide range of damaging alterations with age. Long-term alterations in the transcriptional potential of a cell are heritable and these changes are called epigenetics. The most studied alteration is the DNA methylation, which can regulate gene expression, often blocking gene transcription. The relationship between epigenetics and aging was proposed many years ago, and a decrease in the genomic global DNA methylation with age was largely observed. In this study we describe the methylation status of SIRT1, IGFBP-3 and CAV1 in a young and an older group of healthy individuals by methylation-specific PCR. SIRT1and IGFBP-3 promoter methylation frequency was significantly higher in the older than in the young adult group. Moreover, when combining promoter methylation status of several genes we observed that the total number of methylated promoters more than 85% of older individuals presented 4 promoters against only 46% of young adults. These findings may suggest that with increasing age there is an epigenetic switching to gene repression. The understanding of age-related genes methylation status can lead to a better comprehension of the role of epigenetic variation in the aging process.