PMID- 8657188
OWN - NLM
STAT- MEDLINE
DCOM- 19960726
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 350
IP  - 1
DP  - 1996 Feb 19
TI  - The beneficial effects of dietary restriction: reduced oxidative damage and 
      enhanced apoptosis.
PG  - 25-34
AB  - There is compelling evidence for the central role of oxidative damage in the 
      aging process and for the participation of reactive oxygen species in tumor 
      initiation and promotion. Caloric restriction (CR) or energy restriction retards 
      age-associated increases in mitochondrial free-radical production and reduces the 
      accumulation of oxidatively damaged cell components. CR has also been shown to 
      slow down age-related declines in various repair capabilities, including some 
      types of DNA repair. It is proposed that inhibitors of mitochondrial electron 
      transport and/or uncouplers of oxidative phosphorylation (rotenone, amytal, 
      amiodarone, valinomycin, etc.), when used at extremely low doses, could mimic the 
      effects of CR in model systems. The objective is to lower mitochondrial 
      free-radical production by decreasing the fraction of electron carriers in the 
      reduced state. In addition to a variety of other effects, CR has been shown to 
      increase the rate of apoptosis, particularly in preneoplastic cells, and in 
      general, to promote elevated levels of free glucocorticoids (GCs). GCs are known 
      to induce tissue-specific apoptosis and to upregulate gap-junction-mediated 
      intercellular communication (GJIC). Tumor promoters like phorbol esters have the 
      opposite effect, in that they inhibit both the process of apoptosis and GJIC. The 
      enzyme poly (ADP-ribose) polymerase (PARP) is thought to play a central role in 
      apoptosis, in a manner that has been highly conserved in evolution. There is good 
      evidence that the apoptosis-associated Ca/Mg-dependent DNA endonuclease is 
      maintained in a latent form by being poly (ADP-ribosylated). Apoptosis would 
      require the removal of this polymer from the endonuclease, and, most likely, its 
      removal from topoisomerase II and histone H1 as well. The role of poly 
      (ADP-ribose) in apoptosis, carcinogenesis, and aging could be studied by the use 
      of modulators of PARP activity (3-aminobenzamide, 3-nitrosobenzamide, 1% ethanol, 
      etc.), inhibitors of poly ADP-ribose) glycohydrolase activity (ethacridine, 43 
      degrees C, etc.), and inhibitors of the PARP-specific protease (interleukin-1 
      beta converting enzyme (ICE)-like protease). Also, it would be of interest to 
      determine if CR can decrease the half-life of poly (ADP-ribose), upregulate GJIC, 
      and modulate the activities of PARP, the glycohydrolase, and the PARP-specific 
      protease, factors potentially important in these processes.
FAU - Wachsman, J T
AU  - Wachsman JT
AD  - Environmental Toxicology Program, National Institute of Environmental Health 
      Sciences, Research Triangle Park, NC 27709, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Hormones)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
MH  - Aging
MH  - Animals
MH  - *Apoptosis
MH  - *Energy Intake
MH  - Hormones/metabolism
MH  - Humans
MH  - Mitochondria/metabolism
MH  - Neoplasms/prevention & control
MH  - *Oxidative Stress
MH  - Poly(ADP-ribose) Polymerases/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
RF  - 75
EDAT- 1996/02/19 00:00
MHDA- 1996/02/19 00:01
CRDT- 1996/02/19 00:00
PHST- 1996/02/19 00:00 [pubmed]
PHST- 1996/02/19 00:01 [medline]
PHST- 1996/02/19 00:00 [entrez]
AID - 0027-5107(95)00087-9 [pii]
AID - 10.1016/0027-5107(95)00087-9 [doi]
PST - ppublish
SO  - Mutat Res. 1996 Feb 19;350(1):25-34. doi: 10.1016/0027-5107(95)00087-9.