A role for p53 in mitochondrial stress response control of longevity in C. elegans

As in the case of aging, many degenerative disorders also result from progressive mitochondrial deterioration and cellular damage accumulation. Therefore, preventing damage accumulation may delay aging and help to prevent degenerative disorders, especially those associated with mitochondrial dysfunction. In the nematode Caenorhabditis elegans a mild mitochondrial dysfunction prolongs the lifespan. We previously proposed that, following a mild mitochondrial dysfunction, protective stress responses are activated in a hormetic-like fashion, and ultimately account for extended animal's lifespan. We recently showed that in C. elegans, lifespan extension induced by reduced expression of different mitochondrial proteins involved in electron transport chain functionality requires p53/cep-1. In this paper we find that reducing the expression of frataxin, the protein defective in patients with Friedreich's ataxia, triggers a complex stress response, and that the associated induction of the antioxidant glutathione-S-transferase is regulated by cep-1. Given the high percentage of homology between human and nematode genes and the conservation of fundamental intracellular pathways between the two species, identification of molecular mechanisms activated in response to frataxin suppression in C. elegans may suggest novel therapeutic approaches to prevent the accumulation of irreversible damage and the consequent appearance of symptoms in Friedreich's ataxia and possibly other human mitochondrial-associated diseases. The same pathways could be exploitable for delaying the aging process ascribed to mitochondrial degeneration.

Torgovnick, Alessandro
Schiavi, Alfonso
Testi, Roberto
Ventura, Natascia
Item Type: 
Journal Article
Publication Title: 
Experimental Gerontology
Journal Abbreviation: 
Exp. Gerontol.
Publication Date: 
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 20172019

Turabian/Chicago Citation

Alessandro Torgovnick, Alfonso Schiavi, Roberto Testi and Natascia Ventura. 2010-08. "A role for p53 in mitochondrial stress response control of longevity in C. elegans." Experimental Gerontology 45: 8-Jul: 550-557. 10.1016/j.exger.2010.02.007.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.exger.2010.02.007 | issn = 1873-6815 | volume = 45 | pages = 550-557 | last = Torgovnick | first = Alessandro | coauthors = Schiavi, Alfonso, Testi, Roberto, Ventura, Natascia | title = A role for p53 in mitochondrial stress response control of longevity in C. elegans | journal = Experimental Gerontology | date = 2010-08 | pmid = | pmc = }} </ref>