Linked Life Data

21297001

Source:http://linkedlifedata.com/resource/pubmed/id/21297001

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2011-4-22
pubmed:abstractText
Telomerase reverse transcriptase (TERT) contributes to the prevention of aging by a largely unknown mechanism that is unrelated to telomere lengthening. The current study used ataxia-telangiectasia mutated (ATM) and TERT doubly deficient mice to evaluate the contributions of 2 aging-regulating molecules, TERT and ATM, to the aging process. ATM and TERT doubly deficient mice demonstrated increased progression of aging and had shorter lifespans than ATM-null mice, while TERT alone was insufficient to affect lifespan. ATM-TERT doubly null mice show in vivo senescence, especially in hematopoietic tissues, that was dependent on p16(INK4a) and p19(ARF), but not on p21. As their HSCs show decreased stem cell activities, accelerated aging seen in these mice has been attributed to impaired stem cell function. TERT-deficient HSCs are characterized by reactive oxygen species (ROS) fragility, which has been suggested to cause stem cell impairment during aging, and apoptotic HSCs are markedly increased in these mice. p38MAPK activation was indicated to be partially involved in ROS-induced apoptosis in TERT-null HSCs, and BCL-2 is suggested to provide a part of the protective mechanisms of HSCs by TERT. The current study demonstrates that TERT mitigates aging by protecting HSCs under stressful conditions through telomere length-independent mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4169-80
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:21297001-Aging, pubmed-meshheading:21297001-Animals, pubmed-meshheading:21297001-Apoptosis, pubmed-meshheading:21297001-Cell Aging, pubmed-meshheading:21297001-Cell Cycle Proteins, pubmed-meshheading:21297001-DNA-Binding Proteins, pubmed-meshheading:21297001-Gene Deletion, pubmed-meshheading:21297001-Hematopoietic Stem Cells, pubmed-meshheading:21297001-Mice, pubmed-meshheading:21297001-Mice, Inbred C57BL, pubmed-meshheading:21297001-Protein-Serine-Threonine Kinases, pubmed-meshheading:21297001-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:21297001-Reactive Oxygen Species, pubmed-meshheading:21297001-Telomerase, pubmed-meshheading:21297001-Telomere, pubmed-meshheading:21297001-Tumor Suppressor Proteins, pubmed-meshheading:21297001-p38 Mitogen-Activated Protein Kinases
pubmed:year
2011
pubmed:articleTitle
Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism.
pubmed:affiliation
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't