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.
Increased
vulnerability
to
seizures
in
aging
has
been
well
documented
both
clinically
and
various
models
of
epilepsy.
Seizures
can
exacerbate
cognitive
decline
that
is
already
prominent
aging.
Senescent
cells
are
thought
contribute
impairment
clearing
senescent
with
senolytic
drugs
improves
function
animal
models.
It
remains
unclear
whether
render
the
aged
brain
vulnerable
seizures.
Here,
we
demonstrate
prophylactic
treatment
Dasatinib
Quercetin
(D&Q)
reduced
seizure
severity
mortality
C57BL/6J
mice.
We
subjected
D&Q
VEH-treated
mice
spatial
memory
testing
before
after
an
acute
insult,
Status
Epilepticus
[SE],
which
leads
epilepsy
development.
found
therapy
improved
injury,
however,
was
not
rescued
SE.
Senescence-related
proteins
p16
senescence-associated
β-galactosidase
were
D&Q-treated
Our
findings
indicate
increase
susceptibility
Thus,
prophylactically
targeting
may
prevent
age-related
vulnerability.
Mechanisms of Ageing and Development,
Год журнала:
2024,
Номер
221, С. 111976 - 111976
Опубликована: Авг. 5, 2024
Human
aging
is
linked
to
bone
loss,
resulting
in
fragility
and
an
increased
risk
of
fractures.
This
primarily
due
age-related
decline
the
function
bone-forming
osteoblastic
cells
accelerated
cellular
senescence
within
microenvironment.
Here,
we
provide
a
detailed
discussion
hypothesis
that
defective
formation
caused
by
skeletal
stem
cells,
as
they
are
main
source
forming
influence
composition
Furthermore,
this
review
discusses
potential
strategies
target
emerging
approach
treat
loss.
Abstract
Cellular
senescence
is
an
established
cause
of
cell
and
tissue
aging.
Senescent
cells
have
been
shown
to
increase
in
multiple
organs
during
aging,
including
the
skin.
Here
we
hypothesized
that
senescent
residing
skin
can
spread
distant
organs,
thereby
accelerating
systemic
aging
processes.
To
explore
this
hypothesis,
initially
observed
several
markers
mice.
Subsequently,
conducted
experiments
wherein
fibroblasts
were
transplanted
into
dermis
young
mice
assessed
various
age‐associated
parameters.
Our
findings
reveal
presence
dermal
layer
leads
increased
both
proximal
distal
host
tissues,
alongside
frailty,
impaired
musculoskeletal
function.
Additionally,
there
was
a
significant
decline
cognitive
function,
concomitant
with
expression
senescence‐associated
within
hippocampus
brain
area.
These
results
support
concept
accumulation
exert
remote
effects
on
other
brain,
potentially
explaining
links
between
disorders
diseases
and,
contributing
physical
associated
Endocrinology and Metabolism,
Год журнала:
2023,
Номер
38(3), С. 295 - 301
Опубликована: Июнь 14, 2023
Osteoporosis
and
type
2
diabetes
(T2D)
are
common
diseases
that
often
coexist.
While
both
of
these
associated
with
poor
bone
quality
increased
fracture
risk,
their
pathogenesis
risk
differs
is
multifactorial.
Mounting
evidence
now
indicates
key
fundamental
mechanisms
central
to
aging
energy
metabolism
exist.
Importantly,
represent
potentially
modifiable
therapeutic
targets
for
interventions
could
prevent
or
alleviate
multiple
complications
osteoporosis
T2D,
including
quality.
One
such
mechanism
has
gained
increasing
momentum
senescence,
which
a
cell
fate
contributes
chronic
diseases.
Accumulating
established
numerous
boneresident
types
become
susceptible
cellular
senescence
old
age.
Recent
work
also
demonstrates
T2D
causes
the
premature
accumulation
senescent
osteocytes
during
young
adulthood,
at
least
in
mice,
although
it
remains
be
seen
other
bone-resident
T2D.
Given
therapeutically
removing
cells
can
age-related
loss
T2D-induced
metabolic
dysfunction,
will
important
future
studies
rigorously
test
whether
eliminate
skeletal
dysfunction
context
as
does
aging.
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.
