Cancer
continues
to
place
a
heavy
burden
on
healthcare
systems
around
the
world.
Although
cancer
survivorship
improve,
cardiotoxicity
leading
cardiomyopathy
and
heart
failure
as
consequence
of
therapy
is
rising,
yesterday's
survivors
are
fast
becoming
today's
patients.
mechanisms
driving
complex,
cellular
senescence
gaining
attention
major
contributor
chemotherapy-induced
and,
therefore,
may
also
represent
novel
therapeutic
target
prevent
this
disease.
Cellular
well-recognized
response
clinical
doses
chemotherapies,
including
anthracyclines,
defined
by
cell
cycle
exit,
phenotypic
alterations
which
include
mitochondrial
dysfunction,
expression
pro-senescent,
pro-fibrotic,
pro-inflammatory
senescence-associated
phenotype.
Senescence
has
an
established
involvement
in
promoting
myocardial
remodeling
during
aging,
studies
have
demonstrated
that
elimination
can
attenuate
pathophysiology
several
cardiovascular
diseases.
Most
recently,
pharmacology-mediated
senescence,
using
class
drugs
termed
senolytics,
been
dysfunction
preclinical
models
cardiotoxicity.
In
review,
we
will
discuss
evidence
anthracycline-induced
causes
long-term
anticancer
consider
how
senescent
phenotype
promote
examine
exciting
possibility
targeting
prove
strategy
or
even
reverse
cardiac
dysfunction.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(13), С. 10788 - 10788
Опубликована: Июнь 28, 2023
Cellular
senescence
is
a
complex
cell
state
that
can
occur
during
physiological
ageing
or
after
exposure
to
stress
signals,
regardless
of
age.
It
dynamic
process
continuously
evolves
in
context-dependent
manner.
Senescent
cells
interact
with
their
microenvironment
by
producing
heterogenous
and
plastic
secretome
referred
as
the
senescence-associated
secretory
phenotype
(SASP).
Hence,
understanding
cross-talk
between
SASP
be
challenging
due
complexity
signal
exchanges.
In
this
review,
we
first
aim
update
definition
its
associated
biomarkers
from
discovery
present
day.
We
detail
regulatory
mechanisms
involved
expression
at
multiple
levels
develop
how
orchestrate
modifications,
focusing
on
extracellular
matrix
neighboring
cells'
fate,
intercellular
communications.
hypotheses
these
microenvironmental
events
may
affect
changes
composition
return.
Finally,
discuss
various
existing
approaches
targeting
clarify
what
currently
known
about
biological
effects
modified
SASPs
cellular
environment.
Abstract
Aging
exhibits
several
hallmarks
in
common
with
cancer,
such
as
cellular
senescence,
dysbiosis,
inflammation,
genomic
instability,
and
epigenetic
changes.
In
recent
decades,
research
into
the
role
of
senescence
on
tumor
progression
has
received
widespread
attention.
While
how
limits
course
cancer
is
well
established,
also
been
found
to
promote
certain
malignant
phenotypes.
The
tumor‐promoting
effect
mainly
elicited
by
a
senescence‐associated
secretory
phenotype,
which
facilitates
interaction
senescent
cells
their
surroundings.
Targeting
therefore
offers
promising
technique
for
therapy.
Drugs
that
pharmacologically
restore
normal
function
or
eliminate
them
would
assist
reestablishing
homeostasis
cell
signaling.
Here,
we
describe
its
occurrence,
impact
biology.
A
“one‐two‐punch”
therapeutic
strategy
first
induced,
followed
use
senotherapeutics
eliminating
introduced.
advances
application
targeting
treatment
are
outlined,
an
emphasis
drug
categories,
strategies
screening,
design,
efficient
targeting.
This
work
will
foster
thorough
comprehension
encourage
additional
within
this
field.
Introduction:
Doxorubicin
(DOX),
a
chemotherapeutic
drug,
induces
senescence
and
increases
the
secretion
of
senescence-associated
secretory
phenotype
(SASP)
in
endothelial
cells
(ECs),
which
contributes
to
DOX-induced
inflammaging.
Metformin,
an
anti-diabetic
demonstrates
senomorphic
effects
on
different
models
senescence.
However,
metformin
have
not
been
reported
before.
Senescent
ECs
exhibit
hyper-inflammatory
response
lipopolysachharide
(LPS).
Therefore,
our
current
work,
we
identified
LPS-induced
hyper-inflammation
senescent
ECs.
Methods:
were
treated
with
DOX
±
for
24
h
followed
by
72
incubation
without
establish
Effects
markers
expression,
SA-β-gal
activity,
SASP
assessed.
To
delineate
molecular
mechanisms,
major
signaling
pathways
determined.
The
effect
LPS
was
determined
stimulating
both
non-senescent
additional
h.
Results:
Metformin
corrected
upregulation
decreased
factors
adhesion
molecules.
These
associated
significant
inhibition
JNK
NF-κB
pathway.
A
observed
compared
blunted
pro-inflammatory
factors.
Conclusion:
Our
study
that
mitigates
ameliorates
LPS.
findings
suggest
may
protect
against
vascular
aging
dysfunction
ameliorate
infection-induced
DOX-treated
cancer
survivors.
The Journal of Cardiovascular Aging,
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 1, 2023
Progressive
age-induced
deterioration
in
the
structure
and
function
of
cardiovascular
system
involves
cardiac
hypertrophy,
diastolic
dysfunction,
myocardial
fibrosis,
arterial
stiffness,
endothelial
dysfunction.
These
changes
are
driven
by
complex
processes
that
interconnected,
such
as
oxidative
stress,
mitochondrial
autophagy,
inflammation,
telomere
In
recent
years,
advances
research
aging,
including
wide
use
animal
models
elucidated
an
abundance
cell
signaling
pathways
involved
these
brought
into
sight
possible
interventions,
which
span
from
pharmacological
agents,
metformin,
sodium-glucose
cotransporter
2-inhibitors,
rapamycin,
dasatinib
quercetin,
to
lifestyle
changes.
Chondrocyte
senescence
and
reduced
lubrication
play
pivotal
roles
in
the
pathogenesis
of
age-related
osteoarthritis
(OA).
In
present
study,
highly
lubricated
drug-loaded
hydrogel
microspheres
are
designed
fabricated
through
radical
polymerization
sulfobetaine
(SB)-modified
hyaluronic
acid
methacrylate
using
microfluidic
technology.
The
copolymer
contains
a
large
number
SB
carboxyl
groups
that
can
provide
high
degree
hydration
form
electrostatic
loading
interactions
with
metformin
(Met@SBHA),
producing
drug
load
for
anti-chondrocyte
senescence.
Mechanical,
tribological,
release
analyses
demonstrated
enhanced
lubricative
properties
prolonged
dissemination
Met@SBHA
microspheres.
RNA
sequencing
(RNA-seq)
analysis,
network
pharmacology,
vitro
assays
revealed
extraordinary
capacity
to
combat
chondrocyte
Additionally,
inducible
nitric
oxide
synthase
(iNOS)
has
been
identified
as
promising
protein
modulated
by
Met
senescent
chondrocytes,
thereby
exerting
significant
influence
on
iNOS/ONOO-/P53
pathway.
Notably,
intra-articular
administration
aged
mice
ameliorated
cartilage
OA
pathogenesis.
Based
findings
this
emerges
an
innovative
strategy
tackling
serving
dual
function
enhancing
joint
mitigating
Journal of Translational Internal Medicine,
Год журнала:
2025,
Номер
13(1), С. 33 - 47
Опубликована: Фев. 1, 2025
Aging
and
age-related
diseases
are
major
drivers
of
multimorbidity
mortality
worldwide.
Cellular
senescence
is
a
hallmark
aging.
The
accumulation
senescent
cells
causally
associated
with
pathogenesis
various
age-associated
disorders.
Due
to
their
promise
for
alleviating
disorders
extending
healthspan,
therapeutic
strategies
targeting
(senotherapies)
as
means
combat
aging
have
received
much
attention
over
the
past
decade.
Among
conventionally
used
approaches,
one
usage
small-molecule
compounds
specifically
exhibit
cytotoxicity
toward
or
inhibit
deleterious
effects
senescence-associated
secretory
phenotype
(SASP).
Alternatively,
there
immunotherapies
directed
at
surface
antigens
upregulated
in
(seno-antigens),
including
chimeric
antigen
receptor
(CAR)
therapies
senolytic
vaccines.
This
review
gives
an
update
current
status
discovery
development
therapies,
translational
progress
from
preclinical
clinical
trials.
We
highlight
challenges
faced
by
senotherapeutic
context
heterogeneity,
aim
offering
novel
perspectives
future
anti-aging
interventions
aimed
enhancing
healthy
longevity.
