Antioxidants Help
Prevent Age-Related
Loss of Energy

Donald J. Reed, Ph.D.
Distinguished Professor of Biochemistry
Director, Environmental Health Sciences Center
Interim Director, Linus Pauling Institute

Photo of Donald J. Reed, Ph.D.    

We are now entering the age of mitochondrial medicine. Over 30 years ago, the first patient to have been recognized as suffering from mitochondrial disease experienced enormous perspiration, thinness, and loss of strength and energy, despite extremely high caloric intake. Over 100 types of mitochondrial diseases are now clinically defined. These diseases can be devastating because the major part of our energy is generated by a process that occurs constantly in hundreds of mitochondria within each of our cells. With age, the production of energy becomes less efficient, leading to age-related diseases that affect the functions of eyes and all types of muscles, including the heart. The best known age-related disease, type II diabetes, has an incidence several times higher in patients with certain mitochondrial diseases. Loss of energy production associated with aging also increases the generation of the oxygen free radicals, superoxide and hydroxyl, as well as hydrogen peroxide, a powerful oxidant. These oxygen derived products are capable of damaging essential cellular constituents including lipids, proteins, and DNA, especially DNA associated with the mitochondria.

Although each of our cells has only one copy of DNA in the nucleus, every mitochondrion has many copies of mitochondrial DNA, which is a small circular molecule that encodes for thirteen essential proteins required to perform the task of energy conservation in the form of adenosine triphosphate (ATP) synthesis. Mitochondrial genes are maternally inherited, as mitochondria from the sperm cell do not enter the fertilized egg. In contrast to the very small number of genes in mitochondrial DNA, nuclear DNA contains approximately 100,000 genes that encode for nearly that many proteins. Both nuclear and mitochondrial DNA require protection to prevent damage by free radicals. Antioxidants, including vitamins C and E and glutathione, a sulfur-containing small peptide, each contribute to protection against free radicals by converting the radicals to harmless products.

Photomicrograph of part of a cell, with the stained mitochondria appearing as dark spots. Part of the rounded nucleas is visible at the top.
I have devoted most of my career to understanding the types of protection provided by antioxidants, especially related to preserving mitochondrial energy production. We have observed that mitochondria require antioxidant protection to prevent transition to a degraded state in which ATP production isimpaired. ATP carries chemical energy in cells; when its energy is transferred, ATP loses a molecule of phosphate and becomes adenosine diphosphate (ADP), which can be converted to ATP again by the re-addition of a phosphate molecule. In diseased mitochondria, however, energy is not put to useful work but released instead as heat. Examples of adverse heat production in biological systems are inflammation associated with arthritis and fever stimulated by infection. ATP is importantly involved in providing the energy for muscle contraction, such as the pumping of blood by the heart and the functions of the eyes and inner ear.

Maintenance of mitochondria requires not only adequate antioxidants but alsro precise regulation of intracellular calcium levels. We have studied the regulation of intracellular calcium and the effects of the loss of calcium regulation on mitochondrial functions. While we do not know much about this process in either normal or diseased cells, there is strong evidence for a physiological role for mitochondrial permeability transition, which is the opening of small pores in the walls of mitochondria. Calcium and other mitochondrial constituents can be released from the mitochondria through these pores, allowing mitochondrial de-energization and the loss of ability to form ATP. Our present and planned studies will develop a better understanding of the age-related loss of energy and strength and suggest novel preventive techniques.

Last updated May, 1997

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