Address for correspondence: Dr. Jaime Miquel, C. Marqués de Campo, 66 (Farmacia), 03700 Denia (Alicante), Spain. Voice: +34-96-5788495; fax: +34-96-5780641.
Ann. N.Y. Acad. Sci. 959: 508-516 (2002).
Harman's free radical theory of aging and our electron-microscopic
finding of an age-related mitochondrial degeneration in the
somatic tissues of the insect
Drosophila melanogaster as well
as in the fixed postmitotic Leydig and Sertoli cells of the
mouse testis led us to propose a mitochondrial theory of aging,
according to which metazoan senescence may be linked to oxygen
stress-injury to the genome and membranes of the mitochondria
of somatic differentiated cells. These concepts attract a great
deal of attention, since, according to recent work, the mitochondrial
damage caused by reactive oxygen species (ROS) and concomitant
decline in ATP synthesis seem to play a key role not only in
aging, but also in the fundamental cellular process of apoptosis.
Although diet supplementation with antioxidants has not been
able to increase consistently the species-characteristic maximum
life span, it results in significant extension of the mean life
span of laboratory animals. Moreover, diets containing high
levels of antioxidants such as vitamins C and E seem able to
reduce the risk of suffering age-related immune dysfunctions
and arteriosclerosis. Presently, the focus of age-related antioxidant
research is on compounds, such as deprenyl, coenzyme Q
10, alpha-lipoic
acid, and the glutathione-precursors thioproline and
N-acetylcysteine,
which may be able to neutralize the ROS at their sites of production
in the mitochondria. Diet supplementation with these antioxidants
may protect the mitochondria against respiration-linked oxygen
stress, with preservation of the genomic and structural integrity
of these energy-producing organelles and concomitant increase
in functional life span.
