Abstract
Cellular
senescence
is
a
key
contributor
to
aging
and
aging-related
diseases,
but
its
metabolic
profiles
are
not
well
understood.
Here,
we
performed
systematic
analysis
of
the
features
four
types
cellular
(replication,
irradiation,
reactive
oxygen
species
[ROS],
oncogene)
in
12
cell
lines
using
genome-wide
modeling
meta-analysis.
We
discovered
that
replicative
ROS-induced
share
common
signature,
marked
by
decreased
lipid
metabolism
downregulated
mevalonate
pathway,
while
irradiation
oncogene-induced
exhibit
more
heterogeneity
divergence.
Our
knockout
simulations
showed
enhancing
administrating
for
instance,
could
reverse
alterations
associated
with
human
tissue
aging,
suggesting
potential
anti-aging
or
lifespan-extending
effect.
Indeed,
experiment
Caenorhabditis
elegans
significantly
increased
lifespan.
study
provides
new
insight
into
landscape
identifies
targets
interventions.
The Journal of Cardiovascular Aging,
Год журнала:
2025,
Номер
5(1)
Опубликована: Янв. 22, 2025
With
the
increase
in
life
expectancy
globally,
challenge
of
dealing
with
aging
becomes
more
prominent.
Aging
is
a
risk
factor
for
several
diseases,
including
cardiovascular
disease.
Mitochondria,
which
have
long
been
studied
relation
to
aging,
play
crucial
role
maintaining
cellular
homeostasis.
However,
there
limitation
interorganellar
communication
as
organisms
age.
The
unfolded
protein
response
mitochondria
(UPRmt)
activated
during
stress
maintain
mitochondrial
homeostasis
and
prevent
accumulation
damaged
mitochondria.
This
involves
signaling
from
nucleus,
leading
transcriptional
changes.
In
context
heart,
this
review
explores
terms
function
morphology.
It
also
discusses
impact
UPRmt
on
cardiac
diseases
such
heart
failure,
acute
myocardial
infarction,
dilated
cardiomyopathy.
highlights
potential
mitochondria-endoplasmic
reticulum
contact
sites
(MERCs)
modulating
aging.
Finally,
it
provides
an
update
molecules
that
induce
activity,
potentially
benefiting
Biology,
Год журнала:
2022,
Номер
11(12), С. 1768 - 1768
Опубликована: Дек. 6, 2022
Despite
progress
in
biomedical
technologies,
cardiovascular
disease
remains
the
main
cause
of
mortality.
This
is
at
least
part
because
current
clinical
interventions
do
not
adequately
take
into
account
aging
as
a
driver
and
are
hence
aimed
suboptimal
targets.
To
achieve
progress,
consideration
needs
to
be
given
role
cell
pathogenesis.
We
propose
model
unifying
fundamental
processes
underlying
most
age-associated
pathologies.
According
this
model,
aging,
leading
senescence,
responsible
for
tissue
changes
age-related
disease.
process,
occurring
due
telomerase
inactivation
telomere
attrition,
affects
all
components
system,
including
cardiomyocytes,
vascular
endothelial
cells,
smooth
muscle
cardiac
fibroblasts,
immune
cells.
The
unified
offers
insights
relationship
between
upstream
risk
factors
downstream
outcomes
explains
why
either
these
have
limited
success.
Potential
therapeutic
approaches
considered
based
on
model.
Because
activity
can
prevent
reverse
gene
therapy
discussed
promising
intervention.
Telomerase
similar
systems
expected
transformational
medicine.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3581 - 3581
Опубликована: Март 22, 2024
Cardiovascular
diseases
are
a
leading
cause
of
morbidity
and
mortality
world-wide.
While
many
factors
like
smoking,
hypertension,
diabetes,
dyslipidaemia,
sedentary
lifestyle,
genetic
can
predispose
to
cardiovascular
diseases,
the
natural
process
aging
is
by
itself
major
determinant
risk.
Cardiac
marked
conglomerate
cellular
molecular
changes,
exacerbated
age-driven
decline
in
cardiac
regeneration
capacity.
Although
phenotypes
well
characterised,
underlying
mechanisms
far
less
explored.
Recent
advances
unequivocally
link
dysregulation
critical
signalling
pathways
fibroblasts,
which
compromises
role
these
cells
maintaining
structural
functional
integrity
myocardium.
Clearly,
identification
fibroblast-specific
that
regulate
fibroblast
function
senescent
myocardium
immense
importance.
In
this
regard,
recent
studies
show
Discoidin
domain
receptor
2
(DDR2),
collagen-activated
tyrosine
kinase
predominantly
located
has
an
obligate
fibrosis.
Incisive
on
basis
dysregulated
heart
would
pave
way
for
effective
strategies
mitigate
rapidly
growing
elderly
population.
Abstract
Cellular
senescence
is
a
key
contributor
to
aging
and
aging-related
diseases,
but
its
metabolic
profiles
are
not
well
understood.
Here,
we
performed
systematic
analysis
of
the
features
four
types
cellular
(replication,
irradiation,
reactive
oxygen
species
[ROS],
oncogene)
in
12
cell
lines
using
genome-wide
modeling
meta-analysis.
We
discovered
that
replicative
ROS-induced
share
common
signature,
marked
by
decreased
lipid
metabolism
downregulated
mevalonate
pathway,
while
irradiation
oncogene-induced
exhibit
more
heterogeneity
divergence.
Our
knockout
simulations
showed
enhancing
administrating
for
instance,
could
reverse
alterations
associated
with
human
tissue
aging,
suggesting
potential
anti-aging
or
lifespan-extending
effect.
Indeed,
experiment
Caenorhabditis
elegans
significantly
increased
lifespan.
study
provides
new
insight
into
landscape
identifies
targets
interventions.
