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in long-‐lived compared to short-‐lived animal species (38). In the present study,
although the atenolol treatment did not decrease mtROSp, the oxidative damage to
mtDNA was significantly lower in heart mitochondria in the atenolol group and
tended to be lower (non significant trend) in SKM mitochondria. Rarely, but
sometimes, the changes in both parameters (mtROSp and mtDNA oxidative damage)
in longevity modifying experiments have been apparently dissociated (39). Maybe
the longest time of drug exposure of the present study can induce an increase in the
mitochondrial mtDNA repair systems, resulting in the decreased 8-‐oxodG levels
observed. There is a systematic negative relationship between tissue membrane fatty
acid unsaturation and longevity in all mammals studied to date (35, 40).
Extraordinarily long-‐lived animals like birds (41, 42), naked mole rats (43), the
echidna (44) and queen honey bees (35) also show a common trait: they also have a
low fatty acid unsaturation degree in their tissue cellular membranes. This makes
their membranes more resistant to lipid peroxidation, since the sensitivity of
membrane lipids to lipid peroxidation increases in an exponential way as a function
of the number of double bonds per fatty acid molecule (17). This also occurs in long-‐
lived wild-‐derived strains of mice when compared to genetically heterogeneous
laboratory mice (45). In our study, the atenolol treatment significantly decreased the
DBI in heart and SKM (11% and 22.35% respectively total decrease) and the PI also
in both tissues (16.76% and 30.66% respectively total decrease). These results are in
general agreement with our previous study in C57BL/6 mice heart, in which the
decrease was 40% for the PI and 30% for the DBI respectively, although this was
observed, at variance with the present investigation, in total heart tissue instead of in
heart and SKMmitochondria (2).
The longevity-‐related decrease in global FA unsaturation is due to a
redistribution between the type of PUFAs present from the highly unsaturated
docosahexaenoic (22:6n-‐3) and sometimes arachidonic (20:4n-‐6) acids in short-‐lived
animal species to the less unsaturated linoleic acid (18:2n-‐6) and, in some cases,
linolenic acid (18:3n-‐3) in the long-‐lived ones at mitochondrial and tissue levels (40).
Among these FAs
,
the one contributing most to the low global fatty acid unsaturation
of long-‐lived animals is 22:6n-‐3. This agrees strikingly well with our results, which
show an important decrease in the amount of docosahexahenoic acid (22:6n-‐3) in the
atenolol treated animals in mitochondria from both tissues. It is also interesting that
the fatty acid showing quantitatively more important increases in long lived
mammals in general is 18:2n-‐6, but in the bird case, important increases occurs
frequently for the monounsaturated oleic acid (18:1n-‐9) in long-‐lived species (46), a
FA with well known beneficial effects in many nutritional studies, and this FA also
increases in our case in the long-‐life atenolol-‐treated group.
