Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 1, 2024
Abstract
Aging
of
the
brain
vasculature
plays
a
key
role
in
development
neurovascular
and
neurodegenerative
diseases,
thereby
contributing
to
cognitive
impairment.
Among
other
factors,
DNA
damage
strongly
promotes
cellular
aging,
however,
genomic
instability
endothelial
cells
(EC)
its
potential
effect
on
homeostasis
is
still
largely
unclear.
We
here
investigated
how
aging
impacts
blood-brain
barrier
(BBB)
function
by
using
excision
repair
cross
complementation
group
1
(ERCC1)-deficient
human
ECs
an
EC-specific
Ercc1
knock
out
(EC-KO)
mouse
model.
In
vitro,
ERCC1-deficient
displayed
increased
senescence-associated
secretory
phenotype
(SASP)
expression,
reduced
BBB
integrity
higher
sprouting
capacities
due
underlying
dysregulation
Dll4-Notch
pathway.
In
line,
EC-KO
mice
showed
more
P21+
cells,
augmented
expression
angiogenic
markers
concomitant
increase
number
pericytes.
Moreover,
leakage
enhanced
cell
adhesion
molecule
accompanied
peripheral
immune
infiltration
into
brain.
These
findings
were
confined
white
matter,
suggesting
regional
susceptibility.
Collectively,
our
results
underline
as
driver
impaired
function,
migration
brain,
observed
during
process.
Biogerontology,
Journal Year:
2025,
Volume and Issue:
26(1)
Published: Jan. 8, 2025
Abstract
Extracellular
vesicles
(EVs)
are
implicated
in
inter-organ
communication,
which
becomes
particularly
relevant
during
aging
and
exercise.
DNA
methylation-based
clocks
reflect
lifestyle
environmental
factors,
while
regular
exercise
is
known
to
induce
adaptive
responses,
including
epigenetic
adaptations.
Twenty
individuals
with
High-fitness
(aged
57.7
±
9.8
years)
twenty
Medium–Low-fitness
57.5
9.7
subjects
provided
blood
samples.
EVs
were
isolated
from
the
samples
using
a
size
exclusion
chromatography
(SEC)-based
method,
their
protein
content
was
analyzed
by
mass
spectrometry
(MS).
Acceleration
of
biological
age
estimator
DNAmFitAge
(AgeAccelFit)
associated
cargo
EVs,
whereas
PhenoAge
GrimAge
acceleration
did
not
show
significant
relationship.
This
finding
suggests
that
aging-modulating
role
may
involve
communication
via
EVs.
Set
Enrichment
Analysis
performed
identify
enriched
Gene
Ontology
(GO)
terms
for
sets
proteins
either
correlated
AgeAccelFit
or
detected
exclusively
high
levels
aerobic
fitness.
The
further
influences
inflammation,
immune
system,
cellular
repair,
adhesion,
metabolism
coagulation.
Our
findings
help
understand
preventive
exercise,
could
be
mediated
part
Alzheimer s & Dementia,
Journal Year:
2024,
Volume and Issue:
20(5), P. 3587 - 3605
Published: March 27, 2024
Despite
numerous
studies
in
the
field
of
dementia
and
Alzheimer's
disease
(AD),
a
comprehensive
understanding
this
devastating
remains
elusive.
Bulk
transcriptomics
have
provided
insights
into
underlying
genetic
factors
at
high
level.
Subsequent
technological
advancements
focused
on
single-cell
omics,
encompassing
techniques
such
as
RNA
sequencing
epigenomics,
enabling
capture
transcripts
chromatin
states
single
cell
or
nucleus
resolution.
Furthermore,
emergence
spatial
omics
has
allowed
study
gene
responses
vicinity
amyloid
beta
plaques
across
various
brain
regions.
With
vast
amount
data
generated,
utilizing
regulatory
networks
to
comprehensively
become
essential.
This
review
delves
some
employed
AD,
explores
discoveries
made
using
these
techniques,
provides
future
field.
Cell Death and Disease,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Jan. 3, 2025
Abstract
Aging
of
the
brain
vasculature
plays
a
key
role
in
development
neurovascular
and
neurodegenerative
diseases,
thereby
contributing
to
cognitive
impairment.
Among
other
factors,
DNA
damage
strongly
promotes
cellular
aging,
however,
genomic
instability
endothelial
cells
(EC)
its
potential
effect
on
homeostasis
is
still
largely
unclear.
We
here
investigated
how
aging
impacts
blood-brain
barrier
(BBB)
function
by
using
excision
repair
cross
complementation
group
1
(ERCC1)-deficient
human
ECs
an
EC-specific
Ercc1
knock
out
(EC-KO)
mouse
model.
In
vitro,
ERCC1-deficient
displayed
increased
senescence-associated
secretory
phenotype
expression,
reduced
BBB
integrity,
higher
sprouting
capacities
due
underlying
dysregulation
Dll4-Notch
pathway.
line,
EC-KO
mice
showed
more
P21
+
cells,
augmented
expression
angiogenic
markers,
concomitant
increase
number
pericytes.
Moreover,
leakage
enhanced
cell
adhesion
molecule
accompanied
peripheral
immune
infiltration
into
brain.
These
findings
were
confined
white
matter,
suggesting
regional
susceptibility.
Collectively,
our
results
underline
as
driver
impaired
function,
sprouting,
migration
brain,
observed
during
process.
GeroScience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 20, 2025
Abstract
Chemotherapy-induced
cognitive
impairment
(CICI),
commonly
referred
to
as
“chemobrain,”
is
a
frequent
and
debilitating
side
effect
experienced
by
cancer
survivors
treated
with
paclitaxel
(PTX).
Preclinical
models
have
shown
that
PTX
promotes
cerebromicrovascular
endothelial
cell
senescence,
leading
chronic
blood–brain
barrier
(BBB)
disruption
neuroinflammation.
Conversely,
the
elimination
of
senescent
cells
through
senolytic
therapies
has
been
restore
BBB
integrity,
reduce
neuroinflammation,
alleviate
PTX-induced
impairment.
In
this
study,
we
tested
hypothesis
senescence
alters
gene
expression
patterns
associated
integrity.
To
investigate
this,
analyzed
scRNA-seq
dataset
from
brains
mice
clinically
relevant
regimen
alongside
vehicle-treated
control
mice.
We
identified
capillary
their
distinct
transcriptomic
profiles
matched
these
known
markers
cellular
senescence.
Our
analysis
confirmed
induces
in
revealed
significant
transcriptional
alterations
linked
impaired
function.
cells,
set
enrichment
(GSEA)
highlighted
downregulated
pathways
junction
assembly
upregulated
involved
extracellular
matrix
remodeling
inflammatory
signaling,
including
Vitronectin
(VTN)
Pleiotrophin
(PTN)
pathways.
Additionally,
cell–cell
communication
reduced
Junctional
Adhesion
Molecule
(JAM)
further
implicating
disruption.
These
findings
highlight
driver
dysfunction
changes
altered
intercellular
signaling.
The
VTN
PTN
state
indicates
shift
toward
vascular
inflammation,
exacerbating
microvascular
fragility
Supported
prior
experimental
findings,
study
suggests
targeting
its
downstream
effects
could
mitigate
impairments.
results
advance
our
understanding
CICI
pathogenesis
provide
foundation
for
developing
therapeutic
strategies
aimed
at
preserving
Neurology,
Journal Year:
2024,
Volume and Issue:
103(11)
Published: Nov. 14, 2024
Age
is
an
important
risk
factor
of
stroke,
cognitive
decline,
and
dementia.
Senescent
endothelial
cells
(ECs)
accumulate
with
advancing
age
through
exposure
to
cellular
stress,
such
as
that
exerted
by
hypertension
diabetes.
These
senescent
ECs
have
altered
characteristics,
tight
junction
proteins,
use
a
more
indiscriminate
transcellular
transport
system,
increased
inflammation,
immune
cell
interactions.
are
the
main
component
blood-brain
barrier
(BBB),
separating
brain
from
systemic
circulation.
As
in
BBB,
their
functioning
results
disruption
barrier.
They
inadequate
barrier-forming
properties,
disrupted
extracellular
matrix,
transcytosis,
resulting
overly
permeable
This
BBB
can
effects
stroke
impairment,
presented
this
review.
Besides
increasing
permeability
also
impair
angiogenesis
vascular
remodeling,
which
ischemic
may
increase
hemorrhagic
transformation
worsen
outcomes.
contribute
microvascular
dysfunction,
cerebral
perfusion
autoregulation.
impairment
along
permeability.
With
aging
population,
there
growing
interest
targeting
senescence.
Several
ongoing
trials
been
evaluating
whether
senolytics
slow
aging,
improve
health,
reduce
decline.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(7), P. 3866 - 3866
Published: March 30, 2024
For
much
of
human
evolution,
the
average
lifespan
was
<40
years,
due
in
part
to
disease,
infant
mortality,
predators,
food
insecurity,
and,
for
females,
complications
childbirth.
Thus,
many
females
did
not
reach
age
menopause
(45–50
years
age)
and
it
is
mainly
past
several
hundred
that
has
been
extended
>75
primarily
public
health
advances,
medical
interventions,
antibiotics,
nutrition.
Therefore,
underlying
biological
mechanisms
responsible
disease
risk
following
must
have
evolved
during
complex
processes
leading
Homo
sapiens
serve
functions
pre-menopausal
state.
Furthermore,
as
a
primary
function
survival
species
effective
reproduction,
likely
most
advantages
having
such
post-menopausal
risks
relate
reproduction
ability
address
environmental
stresses.
This
opinion/perspective
will
be
discussed
context
how
could
enhance
with
improved
offspring,
perhaps
why
are
preserved.
Not
all
exhibit
this
set
diseases,
those
who
do
develop
diseases
conditions.
The
state
operate
unified
complex,
but
independent
variables,
potential
some
overlap.
there
would
heterogeneity
if
factors
essential
reproductive
also
concept
sets
reversible
epigenetic
changes
associated
puberty,
pregnancy,
lactation
offered
explain
observations
regarding
distribution
conditions
their
roles
reproduction.
While
involvement
an
system
dynamic
“modification-demodification-remodification”
paradigm
contributing
hypothesis
at
point,
validation
lead
better
understanding
commonalities
may
future
interventions
control
after
menopause.
