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Exercise training initiated in late middle age attenuates cardiac fibrosis and advanced glycation end-product accumulation in senescent rats
journal contribution
posted on 2014-02-01, 00:00 authored by K J Wright, M M Thomas, Andrew BetikAndrew Betik, D Belke, R T HeppleWhile it has long been postulated that exercise training attenuates the age-related decline in heart function normally associated with increased fibrosis and collagen cross-linking, the potential benefits associated with exercise training initiated later in life are currently unclear. To address this question, Fischer 344 × Brown Norway F1 rats underwent treadmill-based exercise training starting in late middle age and continued into senescence (35 mo) and were compared with age-matched sedentary rats. Hearts were examined for fibrosis and advanced glycation end-products in the subendocardial layer of left ventricular cross-sections. Genes for collagen synthesis and degradation were assessed by polymerase chain reaction, and matrix metalloproteinase (MMP) activity was assessed by EnzChek® Gelatinase/Collagenase Assay Kit. Exercise training of late middle-aged rats attenuated fibrosis and collagen cross-linking, while also reducing age-related mortality between late middle age and senescence. This training was also associated with an attenuated advanced glycation end-product (AGE) accumulation with aging, suggesting a decrease in collagen cross-linking. Conversely, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression, TIMP and MMP1 protein expression, and MMP activity increased with age but were not significantly impacted by exercise training. While our results demonstrate that exercise training in late middle age attenuates age-related mortality and cardiac fibrosis and is accompanied by attenuated AGE accumulation indicative of less collagen cross-linking, the mechanisms explaining this attenuated replacement fibrosis did not appear to involve altered TIMP1 expression, or MMP protein and activity.
History
Journal
Experimental gerontologyVolume
50Pagination
9 - 18Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0531-5565eISSN
1873-6815Language
engPublication classification
C Journal article; C1.1 Refereed article in a scholarly journalCopyright notice
2013, Elsevier Inc.Usage metrics
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No categories selectedKeywords
�AGEANOVAAdvanced glycation end-productsAgingDXAECMETEndurance exerciseF344BNF1FibrosisFischer 344 Brown Norway F1 hybrid ratGAPDHHeartLVMMPMatrix metalloproteinasesRT-PCRTIMPTTBSTris-buffered saline (+0.5% Tween)WGAadvanced glycation end-productanalysis of variancedual energy X-ray absorptiometryexercise trainingextracellular matrixglyceraldehyde 3-phosphate dehydrogenaseleft ventriclematrix metalloproteinasepercent body fatreverse transcription polymerase chain reactiontissue inhibitor of matrix metalloproteinasewheat germ agglutininAnimalsCollagenGlycation End Products, AdvancedMyocardiumPhysical Conditioning, AnimalRatsRats, Inbred BNRats, Inbred F344Survival AnalysisTissue Inhibitor of Metalloproteinase-1Science & TechnologyLife Sciences & BiomedicineGeriatrics & GerontologyCOLLAGEN CROSS-LINKINGMUSCLE AEROBIC FUNCTIONHEART-FAILUREDIASTOLIC DYSFUNCTIONSKELETAL-MUSCLEMYOCARDIAL COLLAGENLEFT-VENTRICLEBROWN-NORWAYFISCHER-344INCREASES
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