Linked Life Data

12175478

Source:http://linkedlifedata.com/resource/pubmed/id/12175478

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-8-14
pubmed:abstractText
As organisms age, an increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling positive cells has been observed in a variety of tissues and cell types. However, whether this represents the increase of apoptosis has not been validated on molecular level. In this study we examined the endogenous activity of caspases that are known to be responsible for the execution of caspase-dependent apoptosis as a function of age in rat liver, lung, and spleen. We demonstrate that the extent of apoptosis in rat liver increases late during the aging process (i.e. 23-27 month) as indicated by the activation of executioner caspases-3, -6, and -7. We also found that the activity of caspase-3, -6, and -7 increased drastically in rat lung and spleen at late stages of aging. Despite reports that the level of Fas mRNA increases with age in rat liver and that Fas system regulates liver homeostasis, we did not detect activation of caspase-8, a key mediator of Fas-induced apoptosis, in aged liver. We also observed increased activities of two caspases, caspase-2 and caspase-9, which are involved in mitochondrion-mediated apoptosis in livers isolated from old rats, and found that hepatocytes isolated from old animals (>23 month) are more sensitive to oxidative stress that targets the mitochondria compared to those isolated from young (6 month) animals. Lastly, we demonstrate that the level of cytochrome c is lower in liver from old animals, probably as a result of expeditious degradation following its release into cytosol. Collectively, our results demonstrate that aging is associated with an increase in the activity of multiple caspases, suggesting that the extent of apoptosis increases as organs age. In the case of rat liver, this increase in caspase activation is more likely associated with the mitochondrial (i.e. intrinsic) pathway rather than the Fas-mediated caspase-8 (extrinsic) pathway of apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0531-5565
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
777-89
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Age-associated increases in the activity of multiple caspases in Fisher 344 rat organs.
pubmed:affiliation
Department of Cellular and Structural Biology, Centre at San Antonio, The University of Texas Health Science, Mail Code 7762, San Antonio, TX 78229-3900, USA.
pubmed:publicationType
Journal Article