PMID- 26414604
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20181202
IS  - 1557-8577 (Electronic)
IS  - 1549-1684 (Linking)
VI  - 18
IP  - 5
DP  - 2015 Oct
TI  - Telomerase Reverse Transcriptase and Peroxisome Proliferator-Activated Receptor gamma 
      Co-Activator-1alpha Cooperate to Protect Cells from DNA Damage and Mitochondrial 
      Dysfunction in Vascular Senescence.
PG  - 479-83
LID - 10.1089/rej.2015.1780 [doi]
AB  - Reduced telomere length with increasing age in dividing cells has been implicated 
      in contributing to the pathologies of human aging, which include cardiovascular 
      and metabolic disorders, through induction of cellular senescence. Telomere 
      shortening results from the absence of telomerase, an enzyme required to maintain 
      telomere length. Telomerase reverse transcriptase (TERT), the protein subunit of 
      telomerase, is expressed only transiently in a subset of adult somatic cells, 
      which include stem cells and smooth muscle cells. A recent report from Xiong and 
      colleagues demonstrates a pivotal role for the transcription co-factor peroxisome 
      proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) in maintaining TERT 
      expression and preventing vascular senescence and atherosclerosis in mice. 
      Ablation of PGC-1alpha reduced TERT expression and increased DNA damage and reactive 
      oxygen species (ROS), resulting in shortened telomeres and vascular senescence. 
      In the ApoE(-/-) mouse model of atherosclerosis, forced expression of PGC-1alpha 
      increased expression of TERT, extended telomeres, and reversed genomic DNA 
      damage, vascular senescence, and the development of atherosclerotic plaques. 
      Alpha lipoic acid (ALA) stimulated expression of PGC-1alpha and TERT and reversed DNA 
      damage, vascular senescence, and atherosclerosis, similarly to ectopic expression 
      of PGC-1alpha. ALA stimulated cyclic adenosine monophosphate (cAMP) signaling, which 
      in turn activated the cAMP response element-binding protein (CREB), a co-factor 
      for PGC-1alpha expression. The possibility that ALA might induce TERT to extend 
      telomeres in human cells suggests that ALA may be useful in treating 
      atherosclerosis and other aging-related diseases. However, further investigation 
      is needed to identify whether ALA induces TERT in human cells, which cell types 
      are susceptible, and whether such changes have clinical significance.
FAU - Mendelsohn, Andrew R
AU  - Mendelsohn AR
AD  - Panorama Research Institute and Regenerative Sciences Institute , Sunnyvale, 
      California.
FAU - Larrick, James W
AU  - Larrick JW
AD  - Panorama Research Institute and Regenerative Sciences Institute , Sunnyvale, 
      California.
LA  - eng
PT  - Comment
PT  - Journal Article
PL  - United States
TA  - Rejuvenation Res
JT  - Rejuvenation research
JID - 101213381
RN  - 0 (Transcription Factors)
SB  - IM
CON - Cell Rep. 2015 Sep 1;12(9):1391-9. PMID: 26299964
MH  - Animals
MH  - Atherosclerosis/*genetics
MH  - Blood Vessels/*growth & development
MH  - *DNA Damage
MH  - *Telomere Shortening
MH  - Transcription Factors/*genetics
EDAT- 2015/09/29 06:00
MHDA- 2016/06/21 06:00
CRDT- 2015/09/29 06:00
PHST- 2015/09/29 06:00 [entrez]
PHST- 2015/09/29 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
AID - 10.1089/rej.2015.1780 [doi]
PST - ppublish
SO  - Rejuvenation Res. 2015 Oct;18(5):479-83. doi: 10.1089/rej.2015.1780.