Page 22 - 71_04

GUSTAVO BARJA AN. R. ACAD. NAC. FARM.

ABSTRACT

Mitochondrial free radicals and longevity

Since the beginning of the XXth century many theories have been proposed to
explain aging. Nowadays, the mitochondrial free radical theory is strongly
supported by the available scientific evidence. In this article published studies on
the relationship between the maximum longevity of animals and their levels of
endogenous antioxidants and mitochondrial rates of oxygen radical generation are
reviewed. Most studies of antioxidant supplementation indicate that these
chemicals can increase mean but not maximum longevity. In addition, endogenous
antioxidant levels negatively correlate with maximum longevity. However, the rate
of production of oxygen radicals at mitochondria and the steady-state levels of
oxidative damage in mitochondrial DNA are lower in long-lived than in short-lived
animal species. Long-lived species also have lower levels of fatty acid unsaturation
in their cellular membranes. On the other hand, caloric restriction, the best know
manipulation that decreases the rate of aging, also lowers mitochondrial free
radical production and oxidative damage to mitochondrial DNA. This decrease
occurs at complex I. These results suggest that common mechanisms have been
used to increase longevity in caloric restriction and during the evolution of animal
species with different aging rates. These mechanisms include a decrease in the rate
of generation of free radicals at mitochondria.

Key words: Free radicals.—mitochondria.—aging.—longevity.—DNA.—fatty
acids.—caloric restriction.

INTRODUCCIÓN

Durante la respiración celular se producen continuamente espe-
cies reactivas derivadas del oxígeno como el radical superóxido, el
peróxido de hidrógeno o el radical hidroxilo (reactive oxygen spe-
cies, ROS). Estas substancias atacan continuamente a todos los tipos
de macromoléculas biológicas. Aunque la producción de ROS puede
aumentar mucho en varias situaciones patológicas, en el individuo
sano hay una producción celular baja pero continua de ROS. La
mayor parte de dicha producción procede de la cadena respiratoria
mitocondrial. La idea de que los radicales libres de origen mitocon-
drial son una de las principales causas del envejecimiento (1) tiene
cada vez más apoyos en la literatura científica (2, 3). Cualquier teo-
ría del envejecimiento debe ser capaz de explicar tres de sus carac-
terísticas principales: es progresivo, universal y endógeno. El ca-

784