The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.
We evaluated the efficacy of three dietary interventions started at middle age (14 months) to retard the aging process in mice. These were supplemental alpha-lipoic acid (LA) or coenzyme Q(10) (CQ) and caloric restriction (CR, a positive control). LA and CQ had no impact on longevity or tumor patterns compared with control mice fed the same number of calories, whereas CR increased maximum life span by 13% (p <.0001) and reduced tumor incidence. To evaluate these interventions at the molecular level, we used microarrays to monitor the expression of 9977 genes in hearts from young (5 months) and old (30 months) mice. LA, CQ, and CR inhibited age-related alterations in the expression of genes involved in the extracellular matrix, cellular structure, and protein turnover. However, unlike CR, LA and CQ did not prevent age-related transcriptional alterations associated with energy metabolism. LA supplementation lowered the expression of genes encoding major histocompatibility complex components and of genes involved in protein turnover and folding. CQ increased expression of genes involved in oxidative phosphorylation and reduced expression of genes involved in the complement pathway and several aspects of protein function. Our observations suggest that supplementation with LA or CQ results in transcriptional alterations consistent with a state of reduced oxidative stress in the heart, but that these dietary interventions are not as effective as CR in inhibiting the aging process in the heart.
Lee
Cheol-Koo
CK
Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI 53706, USA.
Pugh
Thomas D
TD
Klopp
Roger G
RG
Edwards
Jode
J
Allison
David B
DB
Weindruch
Richard
R
Prolla
Tomas A
TA
D000465:Algorithms; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight; D031204:Caloric Restriction; D003067:Coenzymes; D003165:Complement System Proteins; D003600:Cytosol / Q000378:metabolism; D019587:Dietary Supplements; D005109:Extracellular Matrix / Q000378:metabolism; D005609:Free Radicals; D005786:Gene Expression Regulation; D008136:Longevity / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D008063:Thioctic Acid / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism*
D000975:Antioxidants; D003067:Coenzymes; D005609:Free Radicals; D009841:Oligonucleotides; D014451:Ubiquinone; D012313:RNA; D008063:Thioctic Acid; D003165:Complement System Proteins; C024989:coenzyme Q10; D010100:Oxygen