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It is known that the low DBI observed in long-‐lived species is due to changes
in the type of unsaturated fatty acids in the membrane composition. There is a
systematic 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 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 (16). Among these
,
the fatty acid contributing most to decrease the
global fatty acid unsaturation degree in long-‐lived animals is 22:6n-‐3. With the
purpose of checking if similar changes occur in our model, we measured the full
fatty acid composition of heart mitochondria membranes. We found that atenolol
treatment in the Wistar rat heart leads to variations in several fatty acids, but
among them, the most important, quantitatively, was the decrease in the highly
unsaturated 22:6n-‐3, which was responsible to a great extent for the decrease in
the PI. This fatty acid is present in tissue cellular membranes at lower levels in
long-‐lived than in short-‐lived animals, including the long-‐lived naked mole-‐rats
(47) and it also decreases after atenolol treatment in C57BL/6 mice (38). In the
present study, moreover, we found other atenolol-‐induced decreases in fatty acids
which were involved in the decrease of fatty acid unsaturation (lower PI):
decreases in 20:4n-‐6, 22:4n-‐6, 22:5n-‐6, 22:5n-‐3 and 22:6n-‐3
,
whereas 18:2n-‐6
increased. It is also interesting that in the senescence-‐accelerated mouse (SAM)
strain, the SAM-‐prone mice had greater levels of the highly polyunsaturated
peroxidation-‐prone fatty acids 22:6 n-‐3 and 20:4n-‐6 and lower levels of the less
peroxidation-‐prone 18:2n-‐6 PUFA in their membranes, and consequently they had
a greater PI than the SAM-‐resistant mice (48,49). SAM-‐prone mice also showed
greater degree of lipid peroxides in their tissues than SAM-‐resistant mice (50).
What are the consequences of this decrease in PI? A low PI (sensitivity to
peroxidation) and DBI (double bound index) confer higher resistance of
membranes to lipid peroxidation and lower lipoxidation-‐dependent damage to
macromolecules. Previous studies have shown that the heart of long-‐lived animals
has lower levels of MDAL, a specific marker of lipoxidation-‐dependent damage to
proteins, compared to short-‐lived species (26). In the present study the fatty acid
unsaturation decrease (lower PI) after atenolol treatment correlated with a
remarkable decrease in MDAL (49% lower in the atenolol group). Lipid
peroxidation generates products like MDAL or hydroxynonenal, but it also
produces secondary free radicals. The decreased fatty acid unsaturation degree in
the atenolol group could thus be responsible for a lower lipid-‐derived secondary
free radical formation, decreased specific lipoxidation markers like MDAL and
damage to other macromolecules (51).
On the other hand, there were no changes in the protein oxidation markers
measured (GSA and AASA), but in contrast, protein glycoxidation
,
quantified as the
