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.

Selenium Status of the Australian Population: Effect of Age, Gender and Cardiovascular Disease

“…There were no significant differences detected for plasma Se or GSH-Px between males and females, however there was a trend for males to have lower levels of Se, especially in the 81 years and over age group. It is plausible that lowered Se levels in males may be associated with the higher morbidity and mortality generally reported in elderly males [22].…”

Decrease in NADPH-Cytochrome P450 Reductase Activity of the Human Heart, Liver and Lungs in the Presence of Alpha-Lipoic Acid

“…Therefore, some SH reagents may cause the reversible inactivation of the CPR. One of them might be a strong antioxidant -␣ -lipoic acid, a well-known essential cofactor for the metabolism of ␣ -keto acid used as a therapeutic agent in liver, heart and neurological diseases [9,[22][23][24] . Moreover, it was reported that the substance interferes with SH-containing enzymes, e.g.…”

Aging hearts and vessels: Masters of adaptation and survival

“…The possibility of identifying factors that modify cardiovascular changes [2,[9][10][11], including lifestyle factors, is reinforced by the substantial variability among older persons in the degree to which these cardiovascular changes that accompany aging occur. Treatments targeting structural factors have begun.…”

“…Senescent cardiac myocytes are characterized by altered metabolic, ionic, and electrical properties due partly to increased myocyte size, altered membrane composition, reduced capacity to maintain ion homeostasis, reduced Ca 2+ tolerance, increased reactive O 2 species levels in response to a variety of stressors, and reduced adaptive capacity to invoke bischemic preconditioning-likeQ intracellular signal transduction for post-stress survival [5][6][7][8][9].…”