p66 ShcA and ageing: Modulation by longevity-promoting agent aurintricarboxylic acid

Orli Sagi, Marina Wolfson, Natalie Utko, Khachik Muradian, Vadim Fraifeld

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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: p66 ShcA-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 p66 Shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313]. There is evidence to implicate p66 ShcA in age-related degenerative pathology, including atherosclerosis, sarcopenia, and Alzheimer's disease. We hypothesized that a low level expression of p66 ShcA could be associated with longevity. Also, we suggested that the level of p66 ShcA 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 p66 ShcA decreases with advanced age. Thirty-six-month-old mice have the lowest, whereas newborns have the highest p66 ShcA levels; (ii) ATA significantly decreases the p66 ShcA 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 p66 ShcA as one of the lifespan determinants in mammals; p66 ShcA therefore represents a potential target for pharmacological longevity-promoting intervention.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
JournalMechanisms of Ageing and Development
Volume126
Issue number2
DOIs
StatePublished - 1 Feb 2005
Externally publishedYes

Keywords

  • Aurintricarboxylic acid
  • C57BL/6 mice
  • Drosophila
  • Metabolic rate
  • Shc proteins
  • Survival

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