ABSTRACT
Inactivation
of
telomerase
(TERT)
in
adipocyte
progenitor
cells
(APC)
expedites
telomere
attrition,
and
the
onset
diabetes
mice
fed
high‐fat
diet
(HFD),
which
promotes
APC
over‐proliferation
replicative
senescence.
Here,
we
show
that
time‐restricted
feeding
or
caloric
restriction
postnatal
development
subsequently
subjected
to
HFD
prevents
attrition
but
not
glucose
intolerance.
This
metabolic
effect
dietary
intervention
was
observed
for
with
TERT
KO
endothelial
myeloid
cells.
To
characterize
telomere‐independent
effects
lineage,
analyzed
knockout
mature
adipocytes
(AD‐TERT‐KO),
do
proliferate
avoid
attrition.
Analysis
from
AD‐TERT‐KO
indicated
reliance
on
glycolysis
decreased
mitochondrial
oxidative
metabolism.
We
have
reduced
cold
tolerance
metabolism
abnormality
indicating
a
defect
adaptive
thermogenesis,
characteristic
aging.
Conversely,
ectopic
expression
brown
adipocytes‐induced
oxidation
thermogenic
gene
expression.
conclude
plays
an
important
non‐canonical
function
mitochondria
adipocytes.
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Фев. 21, 2025
Normal
aging
alters
brain
functions
and
phenotypes.
However,
it
is
not
well
understood
how
astrocytes
are
impacted
by
aging,
nor
they
contribute
to
neuronal
dysfunction
disease
risk
as
organisms
age.
Here,
we
examine
the
transcriptional,
cell
biology,
functional
differences
in
across
normal
aging.
Astrocytes
at
baseline
heterogenous,
responsive
their
environments,
critical
regulators
of
microenvironments
function.
With
increasing
age,
adopt
different
immune-related
senescence-associated
states,
which
relate
organelle
loss
homeostasis
maintenance,
both
autonomously
non-cell
autonomously.
These
perturbed
states
increasingly
associated
with
age-related
onset
neurodegeneration,
suggesting
that
astrocyte
a
compelling
target
for
future
manipulation
prevention
disease.
As
we
age,
our
immune
system’s
ability
to
effectively
respond
pathogens
declines,
a
phenomenon
known
as
immunosenescence.
This
age-related
deterioration
affects
both
innate
and
adaptive
immunity,
compromising
function
leading
chronic
inflammation
that
accelerates
aging.
Immunosenescence
is
characterized
by
alterations
in
cell
populations
impaired
functionality,
resulting
increased
susceptibility
infections,
diminished
vaccine
efficacy,
higher
prevalence
of
diseases.
Chronic
low-grade
further
exacerbates
these
issues,
contributing
decline
overall
health
resilience.
review
delves
into
the
characteristics
immunosenescence
examines
various
intrinsic
extrinsic
factors
aging
how
hallmarks
fates
can
play
crucial
role
this
process.
Additionally,
it
discusses
impact
sex,
social
determinants,
gut
microbiota
on
aging,
illustrating
complex
interplay
altering
function.
Furthermore,
concept
resilience
explored,
focusing
metrics
for
assessing
identifying
strategies
enhance
These
include
lifestyle
interventions
such
diet,
regular
physical
activity,
stress
management,
use
gerotherapeutics
other
approaches.
Understanding
mitigating
effects
are
developing
support
robust
responses
aged
individuals.
The
ovary
is
the
first
organ
to
age
in
human
body,
affecting
both
fertility
and
overall
health.
However,
biological
mechanisms
underlying
ovarian
aging
remain
poorly
understood.
Here
we
present
a
comprehensive
single-nuclei
multi-omics
atlas
of
four
young
(ages
23–29
years)
reproductively
aged
49–54
ovaries.
Our
analyses
reveal
coordinated
changes
transcriptomes
chromatin
accessibilities
across
cell
types
during
aging,
notably
mTOR
signaling
being
prominent
ovary-specific
pathway.
Cell-type-specific
regulatory
networks
enhanced
activity
transcription
factor
CEBPD
ovary.
Integration
our
data
with
genetic
variants
associated
at
natural
menopause
demonstrates
global
impact
functional
on
gene
types.
We
nominate
non-coding
variants,
their
target
genes
mechanisms.
This
provides
valuable
resource
for
understanding
cellular,
molecular
basis
aging.
cellular
are
incompletely
authors
provide
RNA
ATAC-seq
tissue
from
donors,
revealing
transcriptomic
epigenomic
highlighting
role
reproductive
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 6, 2025
Abstract
Cellular
senescence
of
brain
cell
types
has
become
an
increasingly
important
perspective
for
both
aging
and
neurodegeneration,
specifically
in
the
context
Parkinson’s
Disease
(PD).
The
characterization
classical
hallmarks
is
a
widely
debated
topic,
whereby
which
phenotype
being
investigated,
such
as
type,
inducing
stressor,
and/or
model
system,
extremely
aspect
to
consider
when
defining
senescent
cell.
Here,
we
describe
type-specific
profile
through
investigation
various
canonical
markers
five
human
midbrain
lines
using
chronic
5-Bromodeoxyuridine
(BrdU)
treatment
DNA
damage-induced
senescence.
We
used
principal
component
analysis
(PCA)
subsequent
regulatory
network
inference
define
unique
common
profiles
well
revealed
senescence-associated
transcriptional
regulators
(SATRs).
Functional
one
identified
regulators,
transcription
factor
AP4
(TFAP4),
further
highlights
type-specificity
expression
hallmarks.
Our
data
indicates
that
SATRs
modulate
induced
key
play
role
PD.
Journal of Neuroendocrinology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
Abstract
Pituitary
tumors
are
characterized
by
slow
proliferation
rates
and
a
high
prevalence
within
the
population.
The
pathogenesis
of
these
remains
incompletely
understood,
although
accumulating
evidence
suggests
that
activation
cellular
senescence
program,
triggered
various
stressors
functioning
as
brake
on
proliferation,
may
contribute
to
their
typically
benign
nature.
Multiple
mediators
response
implicated
in
this
process.
Interleukin‐6
(IL‐6),
proinflammatory
cytokine,
plays
dual
role
pituitary
tumor
biology.
It
is
involved
both
physiological
growth
senescence‐associated
secretory
phenotype
(SASP),
where
it
mediates
paracrine‐proliferative
signals.
In
addition
its
functions,
IL‐6
has
been
regulation
through
non‐secretory
mechanisms.
Other
factors,
such
hormone
(GH),
tumor‐transforming
gene
(PTTG),
interactions
microenvironment,
including
immune
cell
dynamics,
also
observed
tumors.
This
review
examines
latest
concerning
tumors,
with
particular
focus
contribution
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 2364 - 2364
Опубликована: Март 6, 2025
In
recent
years,
evidence
of
the
existence
cellular
senescence
in
central
nervous
system
has
accumulated.
ischemic
stroke,
been
suggested
as
an
unidentified
pathophysiological
mechanism,
prompting
research
into
neuroprotective
potential
senolytic
drugs.
This
study
aims
to
provide
spatio-temporal
brain
following
stroke
and
elucidate
involved
pathways
cell
types.
We
focused
on
most
established
markers
senescence:
cycle
arrest
(p16,
p21);
lysosomal
activity
(senescence-associated
β-galactosidase
[SA-β-gal]);
senescence-associated
secretory
phenotype
([SASP];
Interleukin-6
[IL-6],
Interleukin-1β
[IL-1β],
Tumor
necrosis
factor
[TNF]);
DNA/nuclear
damage
(Checkpoint
kinase
1
[Chk1],
Checkpoint
2
[Chk2],
Lamin
B1
[LB1]).
Male
Wistar
rats
underwent
60
min
transient
middle
cerebral
artery
occlusion,
followed
by
24
h
3,
7,
14
days
recovery.
Our
results
show
significant
increases
p16
expression,
particularly
neurons
microglia/macrophages;
SA-β-gal
accumulation
infarcted
tissue;
SASP
early
after
reperfusion;
changes
Chk1,
Chk2,
LB1
at
days.
Overall,
our
findings
lend
support
microglia/macrophages.
However,
there
is
still
room
gain
further
insight
role
pathophysiology
implementation
successful
therapy.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 7, 2025
The
capacity
to
regenerate
myelin
in
the
central
nervous
system
diminishes
with
age.
This
decline
is
particularly
evident
multiple
sclerosis
(MS),
a
chronic
demyelinating
disease.
Whether
cellular
senescence,
hallmark
of
aging,
contributes
remyelination
impairment
remains
unknown.
Here,
we
show
that
senescent
cells
accumulate
within
demyelinated
lesions
after
injury,
and
treatments
senolytics
enhances
young
middle-aged
mice
but
not
aged
mice.
In
mice,
observe
upregulation
senescence-associated
transcripts,
primarily
microglia
macrophages,
demyelination,
followed
by
reduction
during
remyelination.
However,
factors
persist
lesions,
correlating
inefficient
Proteomic
analysis
secretory
phenotype
(SASP)
reveals
elevated
levels
CCL11/Eotaxin-1
which
found
inhibit
oligodendrocyte
maturation.
These
results
suggest
therapeutic
targeting
SASP
components,
such
as
CCL11,
may
improve
aging
MS.
impact
on
authors
treatment
following
demyelination
young,
these
effects
are
mediated
including
CCL11.
