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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

Alexander M. Aliper1,2, Antonei Benjamin Csoka3,4, Anton Buzdin1,5, Tomasz Jetka6, Sergey Roumiantsev1,7,8, Alexey Moskalev1,8,10, Alex Zhavoronkov1,2,8,9
  • 1Insilico Medicine, Inc., Johns Hopkins University, ETC, B301, MD 21218, USA
  • 2Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
  • 3Vision Genomics LLC, Washington, DC 20011, USA
  • 4Epigenetics Laboratory, Dept. of Anatomy, Howard University, Washington DC 20059, USA
  • 5Pathway Pharmaceuticals, Limited, 56 Gloucester Rd, Wan Chai, Hong Kong
  • 6Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-106 Warsaw, Poland
  • 7Pirogov Russian National Research Medical University, Moscow, 117997, Russia
  • 8Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141700, Russia
  • 9The Biogerontology Research Foundation, BGRF, London W1J 5NE, UK
  • 10George Mason University, Fairfax, VA 22030, USA
Received: August 13, 2014Accepted: January 7, 2015Published: January 9, 2015
https://doi.org/10.18632/aging.100717

Copyright: © 2015 Aliper et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.