title: Response of the senescent heart to stress: clinical therapeutic strategies and quest for mitochondrial predictors of biological age.
abstract: The aging heart has an impaired response to many kinds of stress. In clinical practice, there is a need for senescence-specific therapies to protect against stress and for biochemical markers of senescence to identify those patients most in need of therapy. In isolated rat hearts, in human tissues, and in a clinical trial, we have shown previously that coenzyme Q(10) has the ability to protect the heart against stress especially in senescence. We recently have devised a regimen of therapy to protect the senescent heart against stress, combining metabolic therapy (coenzyme Q(10), alpha lipoic acid, magnesium orotate, and omega 3 polyunsaturated fatty acids) with physical exercise and mental stress reduction. The preliminary results of this program are promising. In an endeavor to predict the likely response of individual senescent hearts to stress, we correlated the tissue load of mitochondrial DNA deletions and total cellular mitochondrial DNA copy number in human cardiac tissue with recovery of the same tissue from ischemia/reperfusion stress. We found that these mitochondrial markers actually were less predictive of impaired response to stress than age alone. We conclude that the aging heart has a diminished capacity to recover from stress that is not readily predictable by cardiac content of intact mitochondrial DNA and that this recovery can be improved by metabolic therapy combined with physical exercise and mental stress reduction.
authors.affiliation: Cardiac Surgical Research Unit, Alfred Hospital and Baker Heart Research Institute (Wynn Domain), Melbourne, Prahran Victoria 3181, Australia. f.rosenfeldt@alfred.org.au
authors.forename: Franklin
authors.initials: F
authors.lastname: Rosenfeldt
authors.forename: Francis
authors.initials: F
authors.lastname: Miller
authors.forename: Phillip
authors.initials: P
authors.lastname: Nagley
authors.forename: Anthony
authors.initials: A
authors.lastname: Hadj
authors.forename: Silvana
authors.initials: S
authors.lastname: Marasco
authors.forename: Deahne
authors.initials: D
authors.lastname: Quick
authors.forename: Freya
authors.initials: F
authors.lastname: Sheeran
authors.forename: Michelle
authors.initials: M
authors.lastname: Wowk
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
mesh_terms: D000375:Aging; D002986:Clinical Trials as Topic; D003067:Coenzymes; D004272:DNA, Mitochondrial / Q000378:metabolism; D015444:Exercise; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D008954:Models, Biological; D015999:Multivariate Analysis; D009206:Myocardium / Q000473:pathology*; D009963:Orotic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011795:Surveys and Questionnaires; D008063:Thioctic Acid / Q000494:pharmacology; D013903:Thoracic Surgery; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D003067:Coenzymes; D004272:DNA, Mitochondrial; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014451:Ubiquinone; D009963:Orotic Acid; D008063:Thioctic Acid; C024989:coenzyme Q10; C104468:magnesium orotate