Research Paper Volume 7, Issue 1 pp 26—37
Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells
- 1 Insilico Medicine, Inc., Johns Hopkins University, ETC, B301, MD 21218, USA
- 2 Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- 3 Vision Genomics LLC, Washington, DC 20011, USA
- 4 Epigenetics Laboratory, Dept. of Anatomy, Howard University, Washington DC 20059, USA
- 5 Pathway Pharmaceuticals, Limited, 56 Gloucester Rd, Wan Chai, Hong Kong
- 6 Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-106 Warsaw, Poland
- 7 Pirogov Russian National Research Medical University, Moscow, 117997, Russia
- 8 Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141700, Russia
- 9 The Biogerontology Research Foundation, BGRF, London W1J 5NE, UK
- 10 George Mason University, Fairfax, VA 22030, USA
Received: August 13, 2014 Accepted: January 7, 2015 Published: January 9, 2015
https://doi.org/10.18632/aging.100717How to Cite
Abstract
For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.