The Journal of Cardiovascular Aging,
Год журнала:
2024,
Номер
4(4)
Опубликована: Ноя. 19, 2024
Cardiovascular
diseases
(CVDs)
and
cancer
are
the
two
leading
causes
of
global
mortality.
Cancer
treatments,
including
radiotherapy
chemotherapy,
can
have
severe
cardiotoxic
side
effects,
raising
concerns
for
patients
increasing
financial
burden
on
healthcare
systems.
Recent
studies
shown
a
link
between
therapy-induced
cardiotoxicity
cardiac
senescence.
Specifically,
systemic
therapies
known
to
induce
senescence,
which
may
directly
result
in
dysfunction
or
enhance
vulnerability
heart
other
stressors.
Besides
anthracyclines,
newer,
more
targeted
such
as
tyrosine
kinase
inhibitors
(TKIs)
also
been
Cellular
senescence
is
triggered
by
DNA
damage,
oncogene
activation,
reactive
oxygen
nitrogen
species,
stressors,
secretion
proinflammatory
factors,
increased
oxidative
stress,
disruption
normal
cellular
functions.
Understanding
molecular
mechanisms
induced
therapy
essential
attenuating
even
preventing
clinically
overt
using
senotherapies
senolytics
senomorphics.
In
this
review,
that
associated
with
CVDs
described
an
emphasis
potential
role
disease
progression.
addition,
particularly
doxorubicin
(DOX),
radiotherapy,
TKIs
lead
highlighted.
Finally,
recent
novel
treating
discussed
focus
targeting
following
treatment.
The
field
remains
its
early
stages,
further
research
required
clarify
how
treatments
contribute
cardiotoxicity.
At
same
time,
identifying
be
safely
combined
drugs
protecting
health
patients.
Abstract
Cellular
senescence
and
the
senescence‐associated
secretory
phenotype
(SASP)
contribute
to
age‐related
arterial
dysfunction,
in
part,
by
promoting
oxidative
stress
inflammation,
which
reduce
bioavailability
of
vasodilatory
molecule
nitric
oxide
(NO).
In
present
study,
we
assessed
efficacy
fisetin,
a
natural
compound,
as
senolytic
vascular
cell
SASP
factors
improve
function
old
mice.
We
found
that
fisetin
decreased
cellular
human
endothelial
culture.
mice,
SASP‐related
inflammation
were
lower
1
week
after
final
dose
oral
intermittent
(1
on—2
weeks
off—1
on
dosing)
supplementation.
Old
fisetin‐supplemented
mice
had
higher
function.
Leveraging
p16‐3MR
transgenic
model
allowing
genetic
clearance
p16
INK4A
‐positive
senescent
cells,
ex
vivo
removal
cells
from
arteries
isolated
vehicle‐
but
not
fisetin‐treated
increased
endothelium‐dependent
dilation,
demonstrating
improved
through
senolysis.
Enhanced
with
was
mediated
NO
reduced
cellular‐
mitochondrial‐related
stress.
Arterial
stiffness
Ex
senolysis
aorta
rings
did
further
mechanical
wall
due
Lower
accompanied
favorable
remodeling.
The
findings
this
study
identify
promising
therapy
for
clinical
translation
target
excess
treat
dysfunction.
Mechanisms of Ageing and Development,
Год журнала:
2024,
Номер
222, С. 111995 - 111995
Опубликована: Окт. 9, 2024
Fisetin,
a
flavonoid
naturally
occurring
in
plants,
fruits,
and
vegetables,
has
recently
gained
attention
for
its
potential
role
as
senotherapeutic
agent
the
treatment
of
age-related
chronic
diseases.
Senotherapeutics
target
senescent
cells,
which
accumulate
with
age
disease,
both
circulating
immune
cell
populations
solid
organs
tissues.
Senescent
cells
contribute
to
development
many
diseases,
primarily
by
eliciting
systemic
inflammation
through
their
senescence-associated
secretory
phenotype.
Here,
we
explore
whether
fisetin
can
eliminate
thereby
alleviate
examining
current
evidence
from
vitro
studies
animal
models
that
investigate
fisetin's
impact
on
well
phase
I/II
trials
various
patient
populations.
We
discuss
application
humans,
including
challenges
future
directions.
Our
review
available
data
suggests
targeting
offers
promising
strategy
managing
multiple
potentially
transforming
healthcare
older
multimorbid
patients.
However,
further
are
needed
establish
safety,
pharmacokinetics,
efficacy
senotherapeutic,
identify
relevant
reliable
outcome
measures
human
trials,
optimize
dosing,
better
understand
possible
limitations
agent.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(12), С. 6793 - 6793
Опубликована: Июнь 20, 2024
Aging
is
a
complex
and
time-dependent
decline
in
physiological
function
that
affects
most
organisms,
leading
to
increased
risk
of
age-related
diseases.
Investigating
the
molecular
underpinnings
aging
crucial
identify
geroprotectors,
precisely
quantify
biological
age,
propose
healthy
longevity
approaches.
This
review
explores
pathways
are
currently
being
investigated
as
intervention
targets
biomarkers
spanning
molecular,
cellular,
systemic
dimensions.
Interventions
target
these
hallmarks
may
ameliorate
process,
with
some
progressing
clinical
trials.
Biomarkers
used
estimate
aging-associated
disease.
Utilizing
biomarkers,
clocks
can
be
constructed
predict
state
abnormal
aging,
diseases,
mortality.
Biological
age
estimation
therefore
provide
basis
for
fine-grained
stratification
by
predicting
all-cause
mortality
well
ahead
onset
specific
thus
offering
window
intervention.
Yet,
despite
technological
advancements,
challenges
persist
due
individual
variability
dynamic
nature
biomarkers.
Addressing
this
requires
longitudinal
studies
robust
biomarker
identification.
Overall,
utilizing
discover
new
drug
develop
opens
frontiers
medicine.
Prospects
involve
multi-omics
integration,
machine
learning,
personalized
approaches
targeted
interventions,
promising
healthier
population.
Antioxidants,
Год журнала:
2023,
Номер
13(1), С. 24 - 24
Опубликована: Дек. 21, 2023
Fisetin
(FIS),
a
senolytic
flavonoid,
mitigates
age-related
neuroprotective
changes.
An
amorphous
FIS
dispersion
with
co-carrier
was
prepared
using
supercritical
fluid
extraction
carbon
dioxide
(scCO2).
Characterisation,
including
powder
X-ray
diffraction
and
Fourier-transform
infrared
spectroscopy,
confirmed
amorphization
assessed
intermolecular
interactions.
The
exhibited
enhanced
solubility,
dissolution
profiles,
bioavailability
compared
to
the
crystalline
form.
In
vitro,
demonstrated
antioxidant
activity
(the
ABTS,
CUPRAC,
DDPH,
FRAP
assays)
effects
by
inhibiting
acetylcholinesterase
butyrylcholinesterase.
modulated
gut
microbiota,
reducing
potentially
pathogenic
gram-negative
bacteria
without
affecting
probiotic
microflora.
These
improvements
in
activities,
microbiome
modulation
suggest
potential
for
optimising
delivery
systems
leverage
its
health-promoting
properties
while
addressing
oral
functionality
limitations.
Frontiers in Veterinary Science,
Год журнала:
2024,
Номер
11
Опубликована: Май 15, 2024
Cellular
senescence,
a
condition
where
cells
undergo
arrest
and
can
assume
an
inflammatory
phenotype,
has
been
associated
with
initiation
perpetuation
of
inflammation
driving
multiple
disease
processes
in
rodent
models
humans.
Senescent
secrete
cytokines,
proteins,
matrix
metalloproteinases,
termed
the
senescence
secretory
phenotype
(SASP),
which
accelerates
aging
processes.
In
preclinical
models,
drug
interventions
"senotherapeutics"
selectively
clear
senescent
represent
promising
strategy
to
prevent
or
treat
age-related
conditions
humans
veterinary
species.
this
review,
we
summarize
current
available
literature
describing
