The universality of bioenergetic disease. Age-associated cellular bioenergetic degradation and amelioration therapy.

Abstract

During the present century there has been a dramatic change in life expectancy in advanced societies, now exceeding 80 years. As distinct from life expectancy, life potential is said to be at least 120 years, so that the continuing increase in knowledge has the potential for further major changes in the survival of humans conceivably in the near future. This presentation will be concerned with one aspect of the development of biomedical advances related in part to a concept of an "age-related universality of bioenergetic disease," and its potential amelioration and proposed impact on age-related disease and lifestyle. Aging is a complex biological process associated with a progressive decline in the physiological and biochemical performance of individual tissues and organs, leading to age-associated disease and senescence. Consideration of the progressive accumulation of mitochondrial DNA mutation with age and the tissue/cellular bioenergy decline associated with the aging process has led us to the proposal of a "universality of bioenergetic disease" and the potential for a redox therapy for the condition. This concept envisages that a tissue-bioenergetic decline will be intrinsic to various diseases of the aged and thereby contribute to their pathology, in particular, heart failure, degenerative brain disease, muscle and vascular diseases, as well as other syndromes. The information and concepts embodied in this proposal will be reviewed under the following headings: (1) mitochondrial DNA deletion mutation in some tissue is very extensive and shows mosaicism; (2) age-associated tissue/cellular bioenergy mosaic closely corresponds to the mtDNA profile; (3) cellular bioenergy as a function of mitochondrial bioenergy, glycolysis, and plasma membrane oxidoreductase; (4) redox therapy for the reenergization of cells, tissues, and whole organs. A redox therapy based on coenzyme Q10 has demonstrated profound alteration in heart function of old rats; no significant effect was observed with young rats.