Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-3-5
pubmed:abstractText
To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of cellular senescence, cell death, telomerase activity, telomere integrity, and cell regeneration were measured in myocytes of aging wild-type mice (WT). These parameters were similarly studied in insulin-like growth factor-1 (IGF-1) transgenic mice (TG) because IGF-1 promotes cell growth and survival and may delay cellular aging. Importantly, the consequences of aging on cardiac stem cell (CSC) growth and senescence were evaluated. Gene products implicated in growth arrest and senescence, such as p27Kip1, p53, p16INK4a, and p19ARF, were detected in myocytes of young WT mice, and their expression increased with age. IGF-1 attenuated the levels of these proteins at all ages. Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation. Reduction in nuclear phospho-Akt and telomerase resulted in telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs increased with age in WT impairing the growth and turnover of cells in the heart. DNA damage and myocyte death exceeded cell formation in old WT, leading to a decreased number of myocytes and heart failure. This did not occur in TG in which CSC-mediated myocyte regeneration compensated for the extent of cell death preventing ventricular dysfunction. IGF-1 enhanced nuclear phospho-Akt and telomerase delaying cellular aging and death. The differential response of TG mice to chronological age may result from preservation of functional CSCs undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes conditions the development of an aging myopathy.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cdkn2a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclins, http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Telomerase, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p14ARF, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
514-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14726476-Humans, pubmed-meshheading:14726476-Animals, pubmed-meshheading:14726476-Mice, pubmed-meshheading:14726476-Phosphorylation, pubmed-meshheading:14726476-Male, pubmed-meshheading:14726476-Aging, pubmed-meshheading:14726476-Cell Division, pubmed-meshheading:14726476-Cell Differentiation, pubmed-meshheading:14726476-Cell Count, pubmed-meshheading:14726476-Biological Markers, pubmed-meshheading:14726476-Multipotent Stem Cells, pubmed-meshheading:14726476-Myocytes, Cardiac, pubmed-meshheading:14726476-Cell Aging, pubmed-meshheading:14726476-Protein Processing, Post-Translational, pubmed-meshheading:14726476-Apoptosis, pubmed-meshheading:14726476-Insulin-Like Growth Factor I, pubmed-meshheading:14726476-Protein-Serine-Threonine Kinases, pubmed-meshheading:14726476-Tumor Suppressor Protein p53, pubmed-meshheading:14726476-Recombinant Fusion Proteins, pubmed-meshheading:14726476-Cell Lineage, pubmed-meshheading:14726476-Tumor Suppressor Proteins, pubmed-meshheading:14726476-Cell Cycle Proteins, pubmed-meshheading:14726476-Mice, Transgenic, pubmed-meshheading:14726476-Proto-Oncogene Proteins, pubmed-meshheading:14726476-Cyclins, pubmed-meshheading:14726476-Proto-Oncogene Proteins c-akt, pubmed-meshheading:14726476-Telomere, pubmed-meshheading:14726476-Oxidative Stress, pubmed-meshheading:14726476-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:14726476-Cyclin-Dependent Kinase Inhibitor p16, pubmed-meshheading:14726476-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:14726476-Telomerase, pubmed-meshheading:14726476-Tumor Suppressor Protein p14ARF
More...