Head: Dr. Efstathios S. Gonos

Research group

Efstathios S. Gonos, Director of Research
Niki Chondrogianni, Senior Research Scientist
George Vallianatos, Research Scientist
Constantina Georgala, Research Scientist
Varvara Trachana, Research Scientist
Avgi Tsolou, Research Scientist
Kostas Voutetakis, Research Officer
Ippoliti Karvouni, Administrative Officer
Areti Silligardaki, Nurse

Research objectives

The Programme of ''Molecular and Cellular Ageing'' focuses on the genetic and environmental factors that are linked to human ageing and longevity. By using functional genomics and systems biology approaches several genes have been cloned which associate with cellular senescence and longevity. Detailed studies on one of the isolated genes have revealed that ApoJ/Clusterin is directly implicated in cell survival signals by inhibiting apoptosis. In parallel the general biochemical mechanisms that relate to ageing are also studied, for example, the telomeres shortening and the function of the proteasome. Emphasis is given to the molecular understanding of the impaired function of the proteasome during ageing as well as to the development of ''proteasome activated'' primary human cells that, importantly, exhibit a considerable delay of senescence. Based on these data, transgenic models have been established and natural compounds have been identified that display proteasome activation properties. These natural products have been used in novel, patent protected, anti-ageing products. Finally the laboratory possesses a collection of samples (biobanks) of donors of different ages, including healthy centenarians and long-lived siblings. These samples are employed to study the effects of various environmental factors to the ageing process as well as to identify gene variants that are linked to longevity.

Young Cells	Aged Cells	Cellular Aeging through Proteosomic Inhibition

Current Awarded European Union Grants:

1. ''Genetics of healthy ageing''. Program: LSH/FP-6/IP (2004-2010).
2. ''Coordination and Consolidation of European Biogerontology: en route towards formation of a European College of Biogerontology''. Program: LSH/FP-6/CA (2005-2010).
3. ''Functional analysis of evolutionary conserved mechanisms of ageing based on advanced proteome analysis''. Program: LSH/FP-6/IP (2006-2011). Deputy Coordinator.
4. ''European study to establish biomarkers of human ageing''. Program: LSH/FP-7/CP (2008-2013).

Patents:

1. B. Jansen, M. Gleave, I.P. Trougakos, E.S. Gonos, M. Signaevsky and E. Beraldi (2003) RNAi probes targeting cancer related proteins (03792075.8-2406-CA0301277).
2. E.S. Gonos, I. Chinou and N. Chondrogianni (2009) Anti-ageing properties of quercetin, 18α-glycyrrhetinic acid and hederagenin and their derivatives (09006147.4-2108). Relative product: ''Quercetin and Oak'' (a series of anti-ageing and anti-wrinkles products) by Korres Natural Products

Selected Publications (2003-; IF> 5):

1. N. Chondrogianni, F.L.L. Stratford, I.P. Trougakos, B. Friguet, A.J. Rivett and E.S. Gonos (2003) Central role of the proteasome in senescence and survival of human fibroblasts: induction of a senescence-like phenotype upon its inhibition and resistance to stress upon its activation. J. Biol. Chem. 278, 28026-28037.
2. I.P. Trougakos, A. So, B. Jansen, M.E. Gleave and E.S. Gonos (2004) Silencing expression of the Clusterin/Apolipoprotein J gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability and cell sensitization to genotoxic and oxidative stress. Cancer Res. 64, 1834-1842.
3. I.P. Trougakos, M. Lourda, G. Agiostratidou, D. Kletsas and E.S. Gonos (2005) Differential effects of clusterin/Apolipoprotein J on cellular growth and survival. Free Rad. Biol. Med. 38, 436-449.
4. N. Chondrogianni, C. Tzavelas, A.J. Pemberton, I.P. Nezis, A.J. Rivett and E.S. Gonos (2005) Overexpression of proteasome β5 subunit increases amount of assembled proteasome and confers ameliorated response to oxidative stress and higher survival rates. J. Biol. Chem. 280, 11840-11850.
5. M Katsiki, N. Chondrogianni, I. Chinou, A.J. Rivett and E.S. Gonos (2007) The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers lifespan extension of human embryonic fibroblasts. Rejuvenation Res. 10, 157-172.
6. E. Mocchegiani M. Malavolta, R. Giacconi, C. Cipriano, L. Costarelli, E. Muti, S. Tesei, C. Giuli, R. Papa, F. Marcellini, E. Mariani, L. Rink, G. Herbein, T. Fulop, D. Monti, J. Jajte, G. Dedoussis, E.S. Gonos, A. Buerkle, B. Friguet, P. Mecocci, M. Colasanti, C. Soti, D. Mazzatti, M. Blasco, R. Aspinall and G. Pawelec (2008) Zinc, metallothioneins and longevity: effect of zinc supplementation on antioxidant response. Rejuvenation Res. 11, 419-23.
7. N. Chondrogianni, I.P. Trougakos, D. Kletsas, Q.M. Chen and E.S. Gonos (2008) Partial proteasome inhibition in human fibroblasts triggers accelerated M1 senescence or M2 crisis depending on the p53 and RB status. Aging Cell 7, 717-32 (cover page).
8. I.P. Trougakos, M. Lourda, M.H. Antonelou, D. Kletsas, V.G. Gorgoulis, I. Papassideri, Y. Zou, L.H. Margaritis, D.A. Boothman and E.S. Gonos (2009) Intracellular Clusterin inhibits mitochondrial apoptosis by suppressing p53-activating stress signals and stabilizing the cytosolic Ku70-Bax protein complex. Clinical Cancer Res. 15, 48-59 (cover page).
9. I.P. Trougakos, J.Y. Djeu, E.S. Gonos and D.A. Boothman (2009) Advances and challenges in basic and translational research on Clusterin. Cancer Res. 69, 403-406.
10. E. Balantinou, I.P. Trougakos, N. Chondrogianni, L.H. Margaritis and E.S. Gonos (2009) Transcriptional and post-translational regulation of clusterin by the two main cellular proteolytic pathways. Free Rad. Biol. Med. 46, 1267-1274.
11. B. Catalgol, I. Ziaja, N. Breusing, T. Jung, A. Hohn, B. Alpertunga, P. Schroeder, N. Chondrogianni, E.S. Gonos, I. Petropoulos, B. Friguet, L.O. Klotz, J. Krutmann and T. Grune (2009) The proteasome is an integral part of solar ultraviolet A radio-induced gene expression. J. Biol. Chem. 284, 30076-30086.
12. S. Kapeta, N. Chondrogianni and E.S. Gonos (2010) Nuclear erythroid factor 2 (Nrf2) mediated proteasome activation delays senescence in human fibroblasts. J. Biol. Chem., in press