Efstathios S. Gonos, Researcher A' Niki Chondrogianni, Researcher B'
Giannis Ninios, Post-doctoral Scientist
Kostas Voutetakis, Research Officer
Maria Lefaki, Ph.D. student
Marianna Kapetanou, Ph.D. student
Mirela Sakellari, Ph.D. student
Nadia Georgila, Research Scientist
Vasia Delitsikou, Research Scientist
Nicol Papaeugeniou, Research Scientist
Konstantina Fillipopoulou, Graduate student
Ippoliti Karvouni, Administrative Officer
The “Molecular and Cellular Aging” team focuses on the genetic and environmental factors that are linked to human aging 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 aging 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 aging 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-aging products. The team also 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 aging process as well as to identify gene variants that are linked to longevity. Current studies focus on the combine use of personalized diagnostic protocols with treatment employing novel anti-aging products.
Cellular Aeging through
European Union Grants (2005-):
“Nutritional Zinc, oxidative stress and immunosenescence: biochemical, genetic and lifestyle implications for healthy ageing”. FOOD/FP-6/STREP
“Genetics of healthy ageing”. LSH/FP-6/IP
“Coordination and Consolidation of European Biogerontology: en route towards formation of a European College of Biogerontology”. LSH/FP-6/CA
“Functional analysis of evolutionary conserved mechanisms of ageing based on advanced proteome analysis”. LSH/FP-6/IP
“European study to establish biomarkers of human ageing”. LSH/FP-7/CP
“New dietary strategies addressing the specific needs of the elderly population for healthy ageing in Europe”. KBBE/FP-7/CP
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 & «Johnson & Johnson Inc» USA
Selected Publications (2005-; IF> 5):
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.
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. FreeRad. Biol. Med. 38, 436-449.
M. Lourda, I.P. Trougakos and E.S. Gonos (2007) Development of resistance to chemotherapeutic drugs in human osteosarcoma cell lines largely depends on up-regulation of Clusterin/Apolipoprotein J. Int. J. Cancer120, 611-622.
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. AgingCell7, 717-32 (coverpage).
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. ClinicalCancerRes. 15, 48-59 (coverpage).
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.
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.
B. Catalgol, I. Ziaja, N. Breusing, T. Jung, A. Höhn, 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.
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. 285, 8171-8184.
C. Sisoula, V. Trachana, C. Patterson and E.S. Gonos (2011). CHIP-dependent p53 regulation occurs specifically during cellular senescence. Free Rad. Biol. Med. 50, 157-165.
D. Jurk, C. Wang, S. Miwa, M. Maddick, V. Korolchuk, A. Tsolou, E.S. Gonos, C. Thrasivoulou, M. Saffrey, K. Cameron and T. von Zglinicki (2012) Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell11, 996-1004.
M. Beekman, H. Blanché, M. Perola, A. Hervonen, V. Bezrukov, E. Sikora, F. Flachsbart, L. Christiansen, A.J. De Craen, T.B. Kirkwood, I.M. Rea, M. Poulain, J.M. Robine, S. Valensin, M.A. Stazi, G. Passarino, L. Deiana, E.S. Gonos, L. Paternoster, T.I. Sørensen, Q. Tan, Q. Helmer, E.B. Van den Akker, J. Deelen, F. Martella, H.J. Cordell, K.L. Ayers, J.W. Vaupel, O. Törnwall, T.E. Johnson, S. Schreiber, M. Lathrop, A. Skytthe, R.G. Westendorp, K. Christensen, J. Gampe, A. Nebel, J.J. Houwing-Duistermaat, E.P. Slagboom and C. Franceschi C (2013) Genome-wide linkage analysis for human longevity: Genetics of Healthy Ageing Study. Aging Cell12, 184-193.
L. Da Silva, M. Godejohann, F.J. Martin, S. Collino, A. Bürkle, M. Moreno-Villanueva, J. Bernhardt, O. Toussaint, B. Grubeck-Loebenstein, E.S. Gonos, E. Sikora, T. Grune, N. Breusing, C. Franceschi, A. Hervonen, M. Spraul and S. Moco (2013) High-Resolution Quantitative Metabolome Analysis of Urine by Automated Flow Injection NMR. Anal. Chem. 85, 5801-5809.
N. Chondrogianni, I. Petropoulos, S. Grimm, K. Georgila, B. Catalgol, B. Friguet, T. Grune and E.S. Gonos (2013) Protein damage, repair and proteolysis. Mol. AspectsMed., in press.
N. Raule, F. Sevini, S. Li, A. Barbieri, F. Tallaro, L. Lomartire, D. Vianello, A. Montesanto, J. Moilanen, V. Bezrukov, H. Blanche, A. Hervonen, K. Christensen, L. Deiana, E.S. Gonos, T.B.L. Kirkwood, P. Kristensen, A. Leon, P.G. Pelicci, M. Poulain, I.M. Rea, J. Remacle, J.M. Robine, S. Schreiber, E. Sikora, P.E. Slagboom, L. Spazzafumo, M.A. Stazi, O. Toussaint, J.W. Vaupel , G. Rose, K. Majamaa, M. Perola, T.E. Johnson, L. Bolund, H. Yang, G. Passarino and C. Franceschi (2013) The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific. AgingCell, in press.