Alexia Gómez & col.
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ralentización del envejecimiento del corazón y el hueso de ratones AC5KO y un
incremento de su longevidad media y máxima (1). Decidimos mimetizar este
modelo en ratas Wistar utilizando atenolol en el agua de bebida para comprobar si
un descenso de estrés oxidativo podría estar implicado. El tratamiento no modificó
la tasa de generación de radicales y el daño oxidativo al ADN del corazón, pero si
redujo el índice de peroxidizabilidad y la lipoxidación proteica de las membranas
mitocondriales, probablemente debido a cambios en las actividades elongasas y
desaturasas.
Palabras clave:
Estrés oxidativo; β-‐bloqueante; Daño lipídico.
1. INTRODUCTION
The mitochondrial free radical theory of aging is currently supported by
both experimental and comparative studies. From these comparative studies, there
are two main factors that can contribute to explain the lower aging rate of long-‐
lived species: a low generation rate of mitochondrial reactive oxygen species
(mitROS) (2,3) and a low membrane fatty acid unsaturation degree (4,5).
Experimental manipulations like dietary or caloric restriction (CR), protein
restriction and methionine restriction (metR) increase longevity in different kind
of animals mainly decreasing the mitROS generation rate (6-‐9), whereas these
manipulations show minor effects on the fatty acid unsaturation degree in most of
these cases (10).
However, modulation of lipid biosynthesis contributes to stress resistance
and longevity in C. elegans mutants, by reduction in lipid peroxidation substrates
and shortening fatty-‐acid chain length to maintain membrane fluidity (11). The
relationship between membrane fatty acid composition and longevity has been
observed in all the animal models studied, including mammals, birds, rodents,
honeybees and humans (12,13). A lower total number of double bounds of
membrane fatty acids makes these molecules more resistant to lipid peroxidation.
Highly unsaturated fatty acids like arachidonic acid (20:4n-‐6) and specially
docosahexaenoic acid (22:6n-‐3) exhibit the highest sensitivity to ROS induced
oxidative damage, their sensitivity increases as a function of the number of double
bonds per fatty acid molecule (14,15) and long-‐lived animal species strongly avoid
their presence in their tissue cellular membranes through tight homeostatic
species-‐specific regulation. (5,13,16)
Different mammalian models of extended lifespan by gene-‐mutation have
been recently described (17,18). Most of them are related to insulin/IGF-‐1-‐like
signaling pathways (19), but there are others like ribosomal S6 protein kinase 1
(S6K1) (20) and AC5KO (1) that can also increase medium and maximum
longevity.
