Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Ноя. 23, 2023
Cellular
senescence
is
a
biological
aging
hallmark
that
plays
key
role
in
the
development
of
neurodegenerative
diseases.
Clinical
trials
are
currently
underway
to
evaluate
effectiveness
senotherapies
for
these
However,
impact
on
brain
and
cognitive
decline
absence
neurodegeneration
remains
uncertain.
Moreover,
patient
populations
like
cancer
survivors,
traumatic
injury
obese
individuals,
obstructive
sleep
apnea
patients,
chronic
kidney
disease
patients
can
suffer
age-related
changes
prematurely,
suggesting
they
may
accelerated
brain.
Understanding
neurocognitive
deficits
linked
conditions
crucial,
especially
considering
rapidly
evolving
field
senotherapeutics.
Such
treatments
could
help
alleviate
early
significantly
reducing
morbidity
healthcare
costs.
This
review
provides
translational
perspective
how
cellular
decline.
We
also
discuss
important
caveats
surrounding
mainstream
senolytics
senomorphics,
present
emerging
evidence
hyperbaric
oxygen
therapy
immune-directed
therapies
as
viable
modalities
senescent
cell
burden.
Haematologica,
Год журнала:
2023,
Номер
108(10), С. 2626 - 2638
Опубликована: Апрель 20, 2023
BCL-XL
and
BCL-2
are
key
anti-apoptotic
proteins
validated
cancer
targets.
753B
is
a
novel
BCL-XL/BCL-2
proteolysis
targeting
chimera
(PROTAC)
that
targets
both
to
the
von
Hippel-Lindau
(VHL)
E3
ligase,
leading
BCLX
L/BCL-2
ubiquitination
degradation
selectively
in
cells
expressing
VHL.
Because
platelets
lack
VHL
expression,
spares
on-target
platelet
toxicity
caused
by
first-generation
dual
inhibitor
navitoclax
(ABT-263).
Here,
we
report
pre-clinical
single-agent
activity
of
against
different
leukemia
subsets.
effectively
reduced
cell
viability
induced
dose-dependent
subset
hematopoietic
lines,
acute
myeloid
(AML)
primary
samples,
vivo
patient-derived
xenograft
AML
models.
We
further
demonstrated
senolytic
753B,
which
enhanced
efficacy
chemotherapy
chemotherapy-induced
cellular
senescence.
These
results
provide
rationale
for
utility
therapy,
suggest
could
produce
an
added
therapeutic
benefit
overcoming
senescence-induced
chemoresistance
when
combined
with
chemotherapy.
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.
AJP Heart and Circulatory Physiology,
Год журнала:
2023,
Номер
326(1), С. H123 - H137
Опубликована: Ноя. 3, 2023
Vascular
aging,
featuring
endothelial
dysfunction
and
large
elastic
artery
stiffening,
is
a
major
risk
factor
for
the
development
of
age-associated
cardiovascular
diseases
(CVDs).
aging
largely
mediated
by
an
excessive
production
reactive
oxygen
species
(ROS)
increased
inflammation
leading
to
reduced
bioavailability
vasodilatory
molecule
nitric
oxide
remodeling
arterial
wall.
Other
cellular
mechanisms
(i.e.,
mitochondrial
dysfunction,
impaired
stress
response,
deregulated
nutrient
sensing,
senescence),
termed
"hallmarks"
or
"pillars"
may
also
contribute
vascular
aging.
Gonadal
which
impacts
women
but
some
men,
modulates
process.
Regular
physical
activity,
including
both
aerobic
resistance
exercise,
first-line
strategy
reducing
CVD
with
Although
exercise
effective
intervention
counter
there
considerable
variation
in
response
training
Aerobic
improves
stiffening
middle-aged/older
men
enhances
function
oxidative
preserving
bioavailability;
however,
similar
improvements
are
not
consistently
observed
estrogen-deficient
postmenopausal
women.
Sex
differences
adaptations
be
related
gonadal
declines
estrogen
that
influence
cellular-molecular
mechanisms,
disconnecting
favorable
signaling
vasculature
induced
training.
The
present
review
will
summarize
current
state
knowledge
on
regular
underlying
involved,
moderating
role
biological
sex.
Ageing Research Reviews,
Год журнала:
2023,
Номер
89, С. 101985 - 101985
Опубликована: Июнь 15, 2023
Old
age
is
associated
with
a
greater
burden
of
disease,
including
neurodegenerative
disorders
such
as
Alzheimer's
disease
and
Parkinson's
well
other
chronic
diseases.
Coincidentally,
popular
lifestyle
interventions,
caloric
restriction,
intermittent
fasting,
regular
exercise,
in
addition
to
pharmacological
interventions
intended
protect
against
age-related
diseases,
induce
transcription
factor
EB
(TFEB)
autophagy.
In
this
review,
we
summarize
emerging
discoveries
that
point
TFEB
activity
affecting
the
hallmarks
aging,
inhibiting
DNA
damage
epigenetic
modifications,
inducing
autophagy
cell
clearance
promote
proteostasis,
regulating
mitochondrial
quality
control,
linking
nutrient-sensing
energy
metabolism,
pro-
anti-inflammatory
pathways,
senescence
promoting
regenerative
capacity.
Furthermore,
therapeutic
impact
activation
on
normal
aging
tissue-specific
development
assessed
contexts
neurodegeneration
neuroplasticity,
stem
differentiation,
immune
responses,
muscle
adaptation,
adipose
tissue
browning,
hepatic
functions,
bone
remodeling,
cancer.
Safe
effective
strategies
activating
hold
promise
strategy
for
multiple
age-associated
diseases
extending
lifespan.
Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Ноя. 23, 2023
Cellular
senescence
is
a
biological
aging
hallmark
that
plays
key
role
in
the
development
of
neurodegenerative
diseases.
Clinical
trials
are
currently
underway
to
evaluate
effectiveness
senotherapies
for
these
However,
impact
on
brain
and
cognitive
decline
absence
neurodegeneration
remains
uncertain.
Moreover,
patient
populations
like
cancer
survivors,
traumatic
injury
obese
individuals,
obstructive
sleep
apnea
patients,
chronic
kidney
disease
patients
can
suffer
age-related
changes
prematurely,
suggesting
they
may
accelerated
brain.
Understanding
neurocognitive
deficits
linked
conditions
crucial,
especially
considering
rapidly
evolving
field
senotherapeutics.
Such
treatments
could
help
alleviate
early
significantly
reducing
morbidity
healthcare
costs.
This
review
provides
translational
perspective
how
cellular
decline.
We
also
discuss
important
caveats
surrounding
mainstream
senolytics
senomorphics,
present
emerging
evidence
hyperbaric
oxygen
therapy
immune-directed
therapies
as
viable
modalities
senescent
cell
burden.
