Mitochondrial Physiology in Health and Disease: Changes with Aging.

Abstract SCI-1

The incidence and cost of the age-related metabolic and degenerative diseases is rising in the face of ever increasing investment. Therefore, something must be missing in our current hypotheses about these diseases. Until now, the prevailing paradigms in Western medicine have been the anatomical paradigm of disease which posits that tissue-specific symptoms are due to tissue-specific structural defects and the Mendelian paradigm of genetics which posits that if a disease is inherited according to the Laws of Mendel it is genetic and if not it is environmental. The epigenome is invoked to explain the environmental modulation of the nuclear gene expression. However, life requires both structure and energy and the over 1500 mitochondrial energy genes are dispersed across the chromosomes plus the maternally inherited mitochondrial DNA. Moreover, the cells and tissues most affected by aging and the age-related disease are those most reliant on mitochondrial energy and the mitochondrial lies at the interface between environmental calories and human physiology, diabetes and obesity. The epigenome and the signal transduction pathways are regulated by protein phosphorylation by ATP, acetylation via acetyl-CoA, and methylation by S-adenosylmethionine, all driven by mitochondrial high energy substrates modulated by available calories. Furthermore, mitochondrial redox chemistry regulates reactive oxygen production and thiol/disulfide chemistry and these also regulate cellular signaling and function. Therefore, bioenergetics and mitochondrial genetics are the missing factors which have inhibited our capacity of address the biology and genetics of the age-related metabolic and degenerative diseases, cancer and aging.