Document Detail

p66ShcA and ageing: modulation by longevity-promoting agent aurintricarboxylic acid.
MedLine Citation:
PMID:  15621204     Owner:  NLM     Status:  MEDLINE    
Many mutations that extend the lifespan of the lower organisms such as C. elegans and Drosophila, are associated with signaling or apoptotic pathways. Recently, such a possibility was shown in mammals: p66ShcA-deficient mice were more resistant to oxidative stress and lived longer than the wild-type animals [Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Randolfi, P.P., Lanfrancone, L., Pelicci, P.G., 1999. The p66Shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313]. There is evidence to implicate p66ShcA in age-related degenerative pathology, including atherosclerosis, sarcopenia, and Alzheimer's disease. We hypothesized that a low level expression of p66ShcA could be associated with longevity. Also, we suggested that the level of p66ShcA could be modulated by a putative longevity-promoting agent aurintricarboxylic acid [aurintricarboxylic acid (ATA); Fraifeld, V., Wolfson, M., Sagi, O., Seidman, R., Asraf, H., Utko, N., Muradian, K., 2002. Effects of anti-apoptotic agent aurintricarboxylic acid on longevity and longevity-associated processes. Biogerontology 3, 48]. We have found that: (i) the level of p66ShcA decreases with advanced age. Thirty-six-month-old mice have the lowest, whereas newborns have the highest p66ShcA levels; (ii) ATA significantly decreases the p66ShcA level in mouse lungs. In addition, the lifespan-prolongation effect of ATA in a Drosophila model was further validated. The results support the suggested role for the p66ShcA as one of the lifespan determinants in mammals; p66ShcA therefore represents a potential target for pharmacological longevity-promoting intervention.
Orli Sagi; Marina Wolfson; Natalie Utko; Khachik Muradian; Vadim Fraifeld
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mechanisms of ageing and development     Volume:  126     ISSN:  0047-6374     ISO Abbreviation:  Mech. Ageing Dev.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2004-12-28     Completed Date:  2005-06-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0347227     Medline TA:  Mech Ageing Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  249-54     Citation Subset:  IM    
Department of Microbiology and Immunology, Faculty of Health Sciences, Center for Multidisciplinary Research in Aging, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
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MeSH Terms
Adaptor Proteins, Signal Transducing / genetics,  metabolism,  physiology*
Aurintricarboxylic Acid / pharmacology*
Blotting, Western
Carbon Dioxide / metabolism
Drosophila melanogaster
Longevity / drug effects*
Lung / metabolism
Mice, Inbred C57BL
Models, Biological
Nitrogen / metabolism
Oxidative Stress
Protein Isoforms
Shc Signaling Adaptor Proteins
Time Factors
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Protein Isoforms; 0/Shc Signaling Adaptor Proteins; 0/Shc1 protein, mouse; 124-38-9/Carbon Dioxide; 4431-00-9/Aurintricarboxylic Acid; 7727-37-9/Nitrogen

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