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n-‐6 and n-‐3 desaturases were also significantly lower in the atenolol treated
animals. This fact can explain the fatty acid unsaturation decrease in the atenolol
group. Desaturation pathways would make available in situ the n-‐6 and n-‐3 fatty
acids to phospholipid acyltransferases in order to remodel the phospholipid acyl
groups. The fact that acyltransferase/n-‐6 desaturase activity ratio is about 10:1 in
tissues (56) reinforces the idea that regulation of desaturases can be the main
limiting factor responsible for the observed fatty acid unsaturation-‐longevity
relationship (40), as well as for the fatty acid changes observed in the present
study. On the other hand, in this study we found a decrease in the following
elongase activities in the atenolol group: ELOVL 1/3, which catalyzes the formation
of saturated fatty acids containing as many as 26-‐carbons; ELOVL 5 (n-‐6), that
catalyzes the initial and rate-‐limiting desaturation of C18:2n-‐6 and C18:3n-‐3 for
the production of longer-‐chain PUFAs; and ELOVL 2/5 (n-‐6) and (n-‐3) which are
involved in PUFA elongation from C20:3n-‐6 and C20:4n-‐3. The lower elongase
activities in atenolol treated animals may be responsible for the decrease in the
acyl chain length in this group.
An intact respiratory chain is needed to get the maximum capacity available
for mitochondrial energy production. Besides, studies in rodents show that the
amount of respiratory complexes in the respiratory chain can change in
experimental modifications that extend life-‐span. Therefore, we measured the
amounts of the four respiratory complexes in our study. There were no differences
in the amount of any of the complexes except in the NDUFA9 complex I subunit,
which was lower in the atenolol group. In previous studies of methionine
restriction (57) and caloric restriction (58) it has been observed that the amount
of complex I was decreased. It is well known that both complex I and complex III
produce ROS in isolated mitochondria (23,59). However, the difference in ROS
production between species with different longevities and between caloric
restricted and
ad libitum
-‐fed animals seems to come exclusively from complex I
(23). Then, the slight decrease observed in the complex I amount in our study can
be responsible for the non-‐significant trend to decrease mitochondrial ROS
production with complex I linked substrates (glutamate/malate), and probably the
adaptive response of the MnSOD content. This decrease would not be as
remarkable as in the case of caloric or methionine restriction, in which the time of
treatment was longer (7 weeks) in contrast to the 15 days of atenolol treatment
implemented here.
AIF is a mitochondrial flavoprotein involved in the assembly/manteinance
of complex I, and besides its role in apoptosis, it is also required for mitochondrial
oxidative phosphorylation (22). Similarly to what was previously reported in
atenolol treated mice (38), in the present investigation AIF did not change after
atenolol treatment, suggesting that the decrease in apoptosis that was observed in
