Page 98 - 79_04

Alexia
Gómez
&
col.

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;
ß-­-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.

614