Linked Life Data

14501182

Source:http://linkedlifedata.com/resource/pubmed/id/14501182

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-9-22
pubmed:abstractText
Genetics versus oxidative stress have been long-standing points of contention among theories seeking to explain the root of aging. Because aging is the highest risk factor for many diseases, it is to our advantage to better understand the biological mechanisms of this process. Caloric restriction has been the only reliable means of extending lifespan in mammalian models until recently. The discovery of mutant strains of mice with increased longevity could be a significant contributor to our understanding of the genetic and molecular basis of human aging. One genetic approach that increases the longevity of mice is the removal of the p66Shc gene, which encodes a protein belonging to a family of adaptors for signal transduction in mitogenic and apoptotic responses. Normally, p66Shc is tyrosine phosphorylated (activated) by various extracellular signals including EGF and insulin. However, serine phosphorylation of p66Shc can occur after oxidative stress either in association with or independently of tyrosine phosphorylation. p66Shc serine phosphorylation has been linked to inactivation of members of forkhead transcription factors, resulting in increased intracellular oxidant levels and increased sensitivity to apoptosis. Knocking out p66Shc allows moderately elevated activity of forkhead transcription factors and better-equipped antioxidant defenses at the cellular level. Recent reports have suggested that methylation of the p66Shc promoter has important implications in its expression regulation. This leads us to hypothesize that the methylation status of the p66Shc promoter may differ between individuals and therefore contribute to variations of longevity. We present evidence arguing that decreasing oxidative stress or increasing resistance to oxidative damage as a result of genetic variation or p66Shc knockout is likely contributing to individual differences in longevity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1389-5729
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-91
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Linking oxidative stress and genetics of aging with p66Shc signaling and forkhead transcription factors.
pubmed:affiliation
Interdisciplinary Graduate Program for Genetics and Genomics, University of Arizona, Tucson, AZ 85724, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't