PMID- 24580844
OWN - NLM
STAT- MEDLINE
DCOM- 20140922
LR  - 20211021
IS  - 1752-0509 (Electronic)
IS  - 1752-0509 (Linking)
VI  - 8
DP  - 2014 Mar 1
TI  - Stress induced telomere shortening: longer life with less mutations?
PG  - 27
LID - 10.1186/1752-0509-8-27 [doi]
AB  - BACKGROUND: Mutations accumulate as a result of DNA damage and imperfect DNA 
      repair machinery. In higher eukaryotes the accumulation and spread of mutations 
      is limited in two primary ways: through p53-mediated programmed cell death and 
      cellular senescence mediated by telomeres. Telomeres shorten at every cell 
      division and cell stops dividing once the shortest telomere reaches a critical 
      length. It has been shown that the rate of telomere attrition is accelerated when 
      cells are exposed to DNA damaging agents. However the implications of this 
      mechanism are not fully understood. RESULTS: With the help of in silico model we 
      investigate the effect of genotoxic stress on telomere attrition and apoptosis in 
      a population of non-identical replicating cells. When comparing the populations 
      of cells with constant vs. stress-induced rate of telomere shortening we find 
      that stress induced telomere shortening (SITS) increases longevity while reducing 
      mutation rate. Interestingly, however, the effect takes place only when genotoxic 
      stresses (e.g. reactive oxygen species due to metabolic activity) are distributed 
      non-equally among cells. CONCLUSIONS: Our results for the first time show how 
      non-equal distribution of metabolic load (and associated genotoxic stresses) 
      combined with stress induced telomere shortening can delay aging and minimize 
      mutations.
FAU - Trusina, Ala
AU  - Trusina A
AD  - Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK 2100, 
      Copenhagen, Denmark. trusina@nbi.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140301
PL  - England
TA  - BMC Syst Biol
JT  - BMC systems biology
JID - 101301827
SB  - IM
MH  - *DNA Damage
MH  - Longevity/*genetics
MH  - *Models, Genetic
MH  - *Mutation Rate
MH  - Telomere Shortening/*genetics
PMC - PMC4015310
EDAT- 2014/03/04 06:00
MHDA- 2014/09/23 06:00
PMCR- 2014/03/01
CRDT- 2014/03/04 06:00
PHST- 2012/03/25 00:00 [received]
PHST- 2014/02/17 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - 1752-0509-8-27 [pii]
AID - 10.1186/1752-0509-8-27 [doi]
PST - epublish
SO  - BMC Syst Biol. 2014 Mar 1;8:27. doi: 10.1186/1752-0509-8-27.