Page 96 - 79_02

A.
Gómez
et
col.

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
SKM
mitochondria
(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.

266