Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(8)
Опубликована: Апрель 16, 2023
Osteocytes
are
specialized
bone
cells
that
orchestrate
skeletal
remodeling.
Senescent
osteocytes
characterized
by
an
activation
of
cyclin-dependent
kinase
inhibitor
p16Ink4a
and
have
been
implicated
in
the
pathogenesis
several
loss
disorders.
In
this
issue
JCI,
Farr
et
al.
now
shown
systemic
removal
senescent
(termed
senolysis)
prevented
age-related
at
spine
femur
mitigated
marrow
adiposity
through
a
robust
effect
on
osteoblasts
osteoclasts,
whereas
cell-specific
senolysis
alone
was
only
partially
effective.
Surprisingly,
transplantation
fibroblasts
into
peritoneum
young
mice
caused
host
osteocyte
senescence
associated
with
loss.
This
refined
concept
effects
remote
may
help
to
develop
improved
senolytic
strategies
against
multisystem
aging
beyond.
Cell,
Год журнала:
2024,
Номер
187(16), С. 4150 - 4175
Опубликована: Авг. 1, 2024
Cellular
senescence
is
a
cell
fate
triggered
in
response
to
stress
and
characterized
by
stable
cell-cycle
arrest
hypersecretory
state.
It
has
diverse
biological
roles,
ranging
from
tissue
repair
chronic
disease.
The
development
of
new
tools
study
vivo
paved
the
way
for
uncovering
its
physiological
pathological
roles
testing
senescent
cells
as
therapeutic
target.
However,
lack
specific
broadly
applicable
markers
makes
it
difficult
identify
characterize
tissues
living
organisms.
To
address
this,
we
provide
practical
guidelines
called
"minimum
information
cellular
experimentation
vivo"
(MICSE).
presents
an
overview
rodent
tissues,
transgenic
models,
non-mammalian
systems,
human
tumors
their
use
identification
specification
cells.
These
uniform,
state-of-the-art,
accessible
toolset
improve
our
understanding
vivo.
Nature Aging,
Год журнала:
2024,
Номер
4(11), С. 1562 - 1581
Опубликована: Сен. 12, 2024
The
accumulation
and
systemic
propagation
of
senescent
cells
contributes
to
physiological
aging
age-related
pathology.
However,
which
cell
types
are
most
susceptible
the
aged
milieu
could
be
responsible
for
senescence
has
remained
unclear.
Here
we
found
that
physiologically
bone
marrow
monocytes/macrophages
(BMMs)
propagate
multiple
tissues,
through
extracellular
vesicles
(EVs),
drive
age-associated
dysfunction
in
mice.
We
identified
peroxisome
proliferator-activated
receptor
α
(PPARα)
as
a
target
microRNAs
within
BMM-EVs
regulates
downstream
effects
on
dysfunction.
Demonstrating
therapeutic
potential,
report
treatment
with
PPARα
agonist
fenofibrate
effectively
restores
tissue
homeostasis
Suggesting
conservation
humans,
cohort
study
7,986
participants,
use
is
associated
reduced
risk
chronic
disease
higher
life
expectancy.
Together,
our
findings
establish
BMMs
can
distant
tissues
cause
dysfunction,
they
provide
supportive
evidence
extend
healthy
lifespan.
The Journal of Cardiovascular Aging,
Год журнала:
2024,
Номер
4(2)
Опубликована: Июнь 3, 2024
Cellular
senescence
in
cardiomyocytes,
characterized
by
cell
cycle
arrest,
resistance
to
apoptosis,
and
the
senescence-associated
secretory
phenotype,
occurs
during
aging
response
various
stresses,
such
as
hypoxia/reoxygenation,
ischemia/reperfusion,
myocardial
infarction
(MI),
pressure
overload,
doxorubicin
treatment,
angiotensin
II,
diabetes,
thoracic
irradiation.
Senescence
heart
has
both
beneficial
detrimental
effects.
Premature
of
myofibroblasts
salutary
effects
MI
overload.
On
other
hand,
persistent
activation
cardiomyocytes
precipitates
cardiac
dysfunction
adverse
remodeling
through
paracrine
mechanisms
MI,
aging,
doxorubicin-induced
cardiomyopathy.
Given
roles
many
conditions,
specific
removal
senescent
cells,
i.e.,
senolysis,
is
great
interest.
Senolysis
can
be
achieved
using
senolytic
drugs
(such
Navitoclax,
Dasatinib,
Quercetin),
pharmacogenetic
approaches
(including
INK-ATTAC
AP20187,
p16-3MR
Ganciclovir,
p16
ablation,
p16-LOX-ATTAC
Cre),
immunogenetic
interventions
(CAR
T
cells
or
vaccination).
In
order
enhance
specificity
decrease
off-target
approaches,
investigation
into
which
develop
and/or
maintain
state
needed.
Cellular
senescence
is
an
aging
mechanism
characterized
by
cell
cycle
arrest
and
a
senescence-associated
secretory
phenotype
(SASP).
Preclinical
studies
demonstrate
that
senolytic
drugs,
which
target
survival
pathways
in
senescent
cells,
can
counteract
age-associated
conditions
span
several
organs.
The
comparative
efficacy
of
distinct
drugs
for
modifying
biomarkers
vivo
has
not
been
demonstrated.
Here,
we
established
aging-
senescence-related
plasma
proteins
tissue
transcripts
changed
old
versus
young
female
male
mice.
We
investigated
responsivity
to
acute
treatment
with
venetoclax,
navitoclax,
fisetin
or
luteolin
transgenic
clearance
aged
p16-InkAttac
discovered
age-dependent
changes
proteins,
including
IL-23R,
CCL5
CA13,
were
reversed
senotherapeutics,
corresponded
expression
differences
tissues,
particularly
the
kidney.
In
from
humans
across
lifespan,
IL-23R
increased
age.
Our
results
reveal
circulating
factors
as
candidate
mediators
interorgan
signal
transduction
translationally
impactful
systemic
burden.
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(12)
Опубликована: Май 16, 2024
Cells
expressing
features
of
senescence,
including
upregulation
p21
and
p16,
appear
transiently
following
tissue
injury,
yet
the
properties
these
cells
or
how
they
contrast
with
age-induced
senescent
remains
unclear.
Here,
we
used
skeletal
injury
as
a
model
identified
rapid
appearance
fracture
p21+
senescence
markers,
mainly
osteochondroprogenitors
(OCHs)
neutrophils.
Targeted
genetic
clearance
suppressed
senescence-associated
signatures
within
callus
accelerated
healing.
By
contrast,
cell
did
not
alter
bone
loss
due
to
aging;
conversely,
p16+
clearance,
known
alleviate
aging,
affect
Following
fracture,
neutrophils
were
enriched
in
signaling
pathways
induce
paracrine
stromal
while
OCHs
highly
secretory
phenotype
factors
impair
formation.
Further
analysis
revealed
an
injury-specific
stem
cell-like
OCH
subset
that
was
inflammatory,
similar
inflammatory
mesenchymal
population
(fibro-adipogenic
progenitors)
evident
muscle
injury.
Thus,
intercommunicating
senescent-like
progenitor
key
regulators
repair
potentially
across
tissues.
Moreover,
our
findings
established
contextual
roles
vs
senescent/senescent-like
may
be
leveraged
for
therapeutic
opportunities.
