Calorie restriction protects against age-related rat aorta sclerosis.
Many theories have been advanced to account for the ageing process, among which the free radical theory deserves much attention. Numerous studies have also shown an association between tissue fibrosis and oxidative stress. Of note, fibrosis may be considered a significant index of tissue ageing. Calorie restriction (CR) has been demonstrated to maintain many physiological processes in a youthful state until a very advanced age. However the anti-ageing mechanisms of CR are still not fully understood. We thus evaluated the effect of CR on oxidative damage and its relationship with fibrosis during ageing. We found a significant increase of both oxidative stress and fibrosis parameters in the aortae from aged vs. young rats. CR reversed both phenomena. CR also protected against the age-associated increase of Jun-N-terminal kinase and p-38 activities, involved in TGFbeta1 expression and signaling. On the contrary, extracellular regulated kinases did not show any age-related change. CR similarly reversed the age-related increase of AP-1 DNA binding activity and the AP-1-dependent increase of vimentin gene expression. In parallel, CR reversed the age-related morphological alterations of the aorta wall cell composition. These data further support the relationship between oxidative stress and fibrosis in different diseases and during ageing. The protection exerted by CR against fibrosclerosis might be due to a decrease of oxidative stress, with consequent decreased MAPK activity and down-regulation of AP-1 activation and of TGFbeta1 expression and signaling.
Castello
Laura
L
Department of Clinical and Biological Sciences, University of Turin, Italy.
Froio
Teresa
T
Cavallini
Gabriella
G
Biasi
Fiorella
F
Sapino
Anna
A
Leonarduzzi
Gabriella
G
Bergamini
Ettore
E
Poli
Giuseppe
G
Chiarpotto
Elena
E
D000199:Actins / Q000378:metabolism; D000375:Aging; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D031204:Caloric Restriction; D002467:Cell Nucleus / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003720:Densitometry; D015536:Down-Regulation; D005355:Fibrosis / Q000473:pathology; D005609:Free Radicals; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015227:Lipid Peroxidation; D020935:MAP Kinase Signaling System; D008297:Male; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D018384:Oxidative Stress; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012598:Sclerosis / Q000473:pathology* / Q000517:prevention & control*; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000199:Actins; D005609:Free Radicals; C508962:Tgfb1 protein, rat; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases