PMID- 15044709
OWN - NLM
STAT- MEDLINE
DCOM- 20040519
LR  - 20231105
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 15
DP  - 2004 Apr 13
TI  - Temporal linkage between the phenotypic and genomic responses to caloric 
      restriction.
PG  - 5524-9
AB  - Caloric restriction (CR), the consumption of fewer calories while avoiding 
      malnutrition, decelerates the rate of aging and the development of age-related 
      diseases. CR has been viewed as less effective in older animals and as acting 
      incrementally to slow or prevent age-related changes in gene expression. Here we 
      demonstrate that CR initiated in 19-month-old mice begins within 2 months to 
      increase the mean time to death by 42% and increase mean and maximum lifespans by 
      4.7 (P = 0.000017) and 6.0 months (P = 0.000056), respectively. The rate of 
      age-associated mortality was decreased 3.1-fold. Between the first and second 
      breakpoints in the CR survival curve (between 21 and 31 months of age), tumors as 
      a cause of death decreased from 80% to 67% (P = 0.012). Genome-wide microarray 
      analysis of hepatic RNA from old control mice switched to CR for 2, 4, and 8 
      weeks showed a rapid and progressive shift toward the gene expression profile 
      produced by long-term CR. This shift took place in the time frame required to 
      induce the health and longevity effects of CR. Shifting from long-term CR to a 
      control diet, which returns animals to the control rate of aging, reversed 90% of 
      the gene expression effects of long-term CR within 8 weeks. These results suggest 
      a cause-and-effect relationship between the rate of aging and the CR-associated 
      gene expression biomarkers. Therefore, therapeutics mimicking the gene-expression 
      biomarkers of CR may reproduce its physiological effects.
FAU - Dhahbi, Joseph M
AU  - Dhahbi JM
AD  - BioMarker Pharmaceuticals, Incorporated, 900 East Hamilton Avenue, Campbell, CA 
      95008, USA.
FAU - Kim, Hyon-Jeen
AU  - Kim HJ
FAU - Mote, Patricia L
AU  - Mote PL
FAU - Beaver, Robert J
AU  - Beaver RJ
FAU - Spindler, Stephen R
AU  - Spindler SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040325
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - *Caloric Restriction
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Genotype
MH  - Longevity/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phenotype
MH  - Survival Analysis
MH  - Time Factors
PMC - PMC397416
EDAT- 2004/03/27 05:00
MHDA- 2004/05/20 05:00
PMCR- 2004/10/13
CRDT- 2004/03/27 05:00
PHST- 2004/03/27 05:00 [pubmed]
PHST- 2004/05/20 05:00 [medline]
PHST- 2004/03/27 05:00 [entrez]
PHST- 2004/10/13 00:00 [pmc-release]
AID - 0305300101 [pii]
AID - 1015524 [pii]
AID - 10.1073/pnas.0305300101 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5524-9. doi: 
      10.1073/pnas.0305300101. Epub 2004 Mar 25.