Partner: Alex Zhavoronkov

Johns Hopkins University (US)

Recent publications
1.Aliper A.M., Csoka A.B., Buzdin A., Jetka T., Roumiantsev S., Moskalev A., Zhavoronkov A., Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells, Aging-US, ISSN: 1945-4589, Vol.7, No.1, pp.26-37, 2015
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.

Keywords:

Progeria, HGPS, Lamin, LMNA, aging, aging pathway, pathway activation, pathway drift, geroscope, geroprotectors, senescence

Affiliations:
Aliper A.M.-Johns Hopkins University (US)
Csoka A.B.-Howard University (US)
Buzdin A.-Johns Hopkins University (US)
Jetka T.-IPPT PAN
Roumiantsev S.-Johns Hopkins University (US)
Moskalev A.-Johns Hopkins University (US)
Zhavoronkov A.-Johns Hopkins University (US)