Am J Gerontol Geriatr | Volume 1, Issue 1 | Research Article | Open Access

ANRIL in Chromosome 9p21 may be Contributing to Human Aging and Modulates Gene Expression in Vascular Endothelial Cells

Ada Congrains¹, Kei Kamide^1,2*, Ryousuke Oguro¹, Chikako Nakama¹, Yuki Imaizumi¹, Tatsuo Kawai¹, Hiroshi Kusunoki¹, Hiroko Yamamoto¹, Miyuki Onishi-Takeya¹, Yasushi Takeya¹, Mai Kabayama², Koichi Yamamoto¹, Ken Sugimoto¹, Kazunori Ikebe³, Yasuyuki Gondo⁴ and Hiromi Rakugi¹

¹Department of Geriatric Medicine and Nephrology, Osaka University, Japan
²Division of Health Sciences, Osaka University Graduate School of Medicine, Japan
³Department of Prosthodontics and Oral Rehabilitation, Osaka University Graduate School of Dentistry, Japan
⁴Department of Clinical Thanatology and Geriatric Behavioral Science, Osaka University Graduate School of
Human Sciences, Japan

^*Correspondance to: Kei Kamide 

Fulltext PDF

Abstract

(CVD) and a hot-spot for multiple disease-associated polymorphisms. The locus encodes for a long non-coding RNA, ANRIL. The disease-associated variants in the region have been correlated with ANRIL expression, suggesting ANRIL mediates these associations. Since most of diseases associated with the locus are common diseases of aging, we sought to investigate the relation between ANRIL expression and age. We measured ANRIL expression by RT-PCR in three groups: 70 years-old, 80 years-old and 90 years-old subjects. ANRIL expression increased dramatically between 70 to 80 years-old. In addition, we profiled the regulatory effects of ANRIL knock-down in endothelial cells. The artificial depletion of ANRIL caused the down-regulation of an upstream regulator of senescence, IL1A, and other inflammatory genes. Conversely, it produced the up-regulation of the transcription factor KLF2, which has athero-protective properties. Our results suggest ANRIL has a pro-atherogenic effect by inducing inflammatory and senescencerelated molecules in endothelial cells. Aggravated senescence and inflammation are characteristic of aging and might be mediated by the age-related changes in ANRIL expression. ANRIL is a promising target for future therapies for many aging-related diseases.

Keywords:

Aging; Atherosclerosis; ANRIL; Senescence; Endothelial dysfunction; Chromosome 9p21; Cardiovascular diseases

Citation:

Congrains A, Kamide K, Oguro R, Nakama C, Imaizumi Y, Kawai T, et al. ANRIL in Chromosome 9p21 may be Contributing to Human Aging and Modulates Gene Expression in Vascular Endothelial Cells. Am J Gerentol Geriatr. 2018; 1(1): 1002.