Abstract
Adult
skeletal
muscle
stem
cells
(MuSCs)
are
essential
for
homeostasis
and
regeneration.
During
aging,
the
number
of
MuSCs
their
regenerative
capacity
gradually
decline
but
underlying
mechanisms
remain
elusive.
Here,
we
identify
Sugt1
(suppressor
G2
allele
SKP1
homolog),
which
is
a
chaperone
kinetochore
function
during
mitosis
regeneration
by
regulating
MuSC
proliferation.
expression
level
low
in
quiescent
highly
induced
when
become
activated
expand
as
proliferating
myoblasts.
Inducible
inactivation
causes
impaired
upon
acute
injury
impairing
Furthermore,
loss
leads
to
cell
cycle
arrest
G2/M
phase
cellular
senescence.
Moreover,
long-term
results
precocious
aging
inhibiting
proliferation
promoting
Mechanistically,
cytosolic
E3
ubiquitin-ligase,
Trim21
protein
interacting
partner
myoblast
cells.
We
further
demonstrate
that
promotes
ubiquitination
p21
via
Trim21;
accumulation
inhibit
progression
stimulates
Collectively,
our
findings
uncover
an
regulator
aging.
Biomedicines,
Год журнала:
2024,
Номер
12(9), С. 1948 - 1948
Опубликована: Авг. 26, 2024
The
aging
of
the
world
population
is
closely
associated
with
an
increased
prevalence
musculoskeletal
disorders,
such
as
osteoporosis,
sarcopenia,
and
osteoarthritis,
due
to
common
genetic,
endocrine,
mechanical
risk
factors.
These
conditions
are
characterized
by
degeneration
bone,
muscle,
cartilage
tissue,
resulting
in
fractures
reduced
mobility.
Importantly,
a
crucial
role
pathophysiology
these
diseases
has
been
proposed
for
cellular
senescence,
state
irreversible
cell
cycle
arrest
induced
factors
DNA
damage,
telomere
shortening,
mitochondrial
dysfunction.
In
addition,
senescent
cells
secrete
pro-inflammatory
molecules,
called
senescence-associated
secretory
phenotype
(SASP),
which
can
alter
tissue
homeostasis
promote
disease
progression.
Undoubtedly,
targeting
their
profiles
could
development
integrated
strategies,
including
regular
exercise
balanced
diet
or
use
senolytics
senomorphs,
improve
quality
life
population.
Therefore,
our
review
aimed
highlight
senescence
age-related
diseases,
summarizing
main
underlying
mechanisms
potential
anti-senescence
strategies
treatment
osteoarthritis.
Frontiers in Endocrinology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 4, 2024
Chronic
or
non-healing
wounds,
such
as
diabetic
foot
ulcers
(DFUs),
venous
leg
(VLUs),
pressure
(PUs)
and
wounds
in
the
elderly
etc.,
impose
significant
biological,
social,
financial
burdens
on
patients
their
families.
Despite
ongoing
efforts,
effective
treatments
for
these
remain
elusive,
costing
United
States
over
US$25
billion
annually.
The
wound
healing
process
is
notably
slower
elderly,
partly
due
to
cellular
senescence,
which
plays
a
complex
role
repair.
High
glucose
levels,
reactive
oxygen
species,
persistent
inflammation
are
key
factors
that
induce
contributing
chronic
failure.
This
suggests
senescence
may
not
only
drive
age-related
phenotypes
pathology
but
also
be
mediator
of
decreased
capacity
trauma
review
analyzes
four
aspects:
characteristics
senescence;
cytotoxic
stressors
related
signaling
pathways;
relationship
between
typical
wounds;
current
future
treatment
strategies.
In
theory,
anti-aging
therapy
influence
healing.
However,
underlying
molecular
mechanism
well
understood.
summarizes
contribute
better
understanding
mechanisms
Oxidative Medicine and Cellular Longevity,
Год журнала:
2022,
Номер
2022, С. 1 - 17
Опубликована: Ноя. 24, 2022
Sarcopenia,
featured
by
the
progressive
loss
of
skeletal
muscle
function
and
mass,
is
associated
with
impaired
stem
cells
(MuSCs)
caused
increasing
oxidative
stress
in
senescent
tissue
during
aging.
Intact
MuSCs
maintains
regenerative
potential
as
well
homeostasis
tissues
Ginsenoside
Rb1,
a
natural
compound
from
ginseng,
exhibited
effects
antioxidation
against
apoptosis.
However,
its
restoring
MuSC
aging
improving
age-related
sarcopenia
remained
unknown.
In
this
study,
we
investigated
role
Rb1
inhibiting
apoptosis
reducing
levels.
We
found
that
inhibited
accumulation
reactive
oxygen
species
(ROS)
protected
to
attenuate
H2O2-induced
cytotoxicity.
also
blocked
stress-induced
activation
caspase-3/9,
which
antagonized
decrease
mitochondrial
content
increase
abnormalities
via
promoting
protein
expression
genes
involved
biogenesis.
Mechanistically,
it
was
proven
exerted
antioxidant
avoided
myoblasts
targeting
core
regulator
nuclear
factor-kappa
B
(NF-κB)
signal
pathway.
Therefore,
these
findings
suggest
may
have
beneficial
prevention
treatment
exhaustion-related
diseases
like
sarcopenia.
Abstract
Adult
skeletal
muscle
stem
cells
(MuSCs)
are
essential
for
homeostasis
and
regeneration.
During
aging,
the
number
of
MuSCs
their
regenerative
capacity
gradually
decline
but
underlying
mechanisms
remain
elusive.
Here,
we
identify
Sugt1
(suppressor
G2
allele
SKP1
homolog),
which
is
a
chaperone
kinetochore
function
during
mitosis
regeneration
by
regulating
MuSC
proliferation.
expression
level
low
in
quiescent
highly
induced
when
become
activated
expand
as
proliferating
myoblasts.
Inducible
inactivation
causes
impaired
upon
acute
injury
impairing
Furthermore,
loss
leads
to
cell
cycle
arrest
G2/M
phase
cellular
senescence.
Moreover,
long-term
results
precocious
aging
inhibiting
proliferation
promoting
Mechanistically,
cytosolic
E3
ubiquitin-ligase,
Trim21
protein
interacting
partner
myoblast
cells.
We
further
demonstrate
that
promotes
ubiquitination
p21
via
Trim21;
accumulation
inhibit
progression
stimulates
Collectively,
our
findings
uncover
an
regulator
aging.
