Neurotherapeutics,
Journal Year:
2025,
Volume and Issue:
22(3), P. e00519 - e00519
Published: Jan. 6, 2025
Cellular
senescence
is
a
cell
state
triggered
by
programmed
physiological
processes
or
cellular
stress
responses.
Stress-induced
senescent
cells
often
acquire
pathogenic
traits,
including
toxic
secretome
and
resistance
to
apoptosis.
When
form
faster
than
they
are
cleared
the
immune
system,
accumulate
in
tissues
throughout
body
contribute
age-related
diseases,
neurodegeneration.
This
review
highlights
evidence
of
brain
their
role
Alzheimer's
disease
(AD),
leading
cause
dementia
older
adults.
We
also
discuss
progress
challenges
senotherapies,
pharmacological
strategies
clear
mitigate
effects,
which
hold
promise
as
interventions
for
AD
related
dementias
(ADRD).
Journal of Clinical Investigation,
Journal Year:
2022,
Volume and Issue:
132(10)
Published: May 15, 2022
Alzheimer's
disease
and
related
dementias
(ADRD)
are
among
the
top
contributors
to
disability
mortality
in
later
life.
As
with
many
chronic
conditions,
aging
is
single
most
influential
factor
development
of
ADRD.
Even
older
adults
who
remain
free
dementia
throughout
their
lives,
cognitive
decline
neurodegenerative
changes
appreciable
advancing
age,
suggesting
shared
pathophysiological
mechanisms.
In
this
Review,
we
provide
an
overview
cognition,
brain
morphology,
neuropathological
protein
accumulation
across
lifespan
humans,
complementary
mechanistic
evidence
from
animal
models.
Next,
highlight
selected
processes
that
differentially
regulated
disease,
including
aberrant
autophagy,
mitochondrial
dysfunction,
cellular
senescence,
epigenetic
changes,
cerebrovascular
inflammation,
lipid
dysregulation.
We
summarize
research
clinical
translational
studies
link
biological
underlying
ADRD
pathogenesis.
Targeting
fundamental
may
represent
a
yet
relatively
unexplored
avenue
attenuate
both
age-related
Collaboration
fields
geroscience
neuroscience,
coupled
new
models
more
closely
align
human
processes,
necessary
advance
novel
therapeutic
discovery
realm.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(8), P. 1628 - 1628
Published: Aug. 17, 2023
Alzheimer’s
disease
(AD)
is
a
brain
disorder
that
progressively
undermines
memory
and
thinking
skills
by
affecting
the
hippocampus
entorhinal
cortex.
The
main
histopathological
hallmarks
of
AD
are
presence
abnormal
protein
aggregates
(Aβ
tau),
synaptic
dysfunction,
aberrant
proteostasis,
cytoskeletal
abnormalities,
altered
energy
homeostasis,
DNA
RNA
defects,
inflammation,
neuronal
cell
death.
However,
oxidative
stress
or
damage
also
evident
commonly
overlooked
considered
consequence
advancement
dementia
symptoms.
control
onset
linked
to
activity
amyloid-β
peptide,
which
may
serve
as
both
antioxidant
pro-oxidant
molecules.
Furthermore,
correlated
with
proteins,
nucleic
acids,
lipids
in
vulnerable
populations,
ultimately
lead
death
through
different
molecular
mechanisms.
By
recognizing
an
integral
feature
AD,
alternative
therapeutic
preventive
interventions
developed
tested
potential
complementary
therapies
for
this
devastating
neurodegenerative
disease.
Communications Biology,
Journal Year:
2023,
Volume and Issue:
6(1)
Published: June 23, 2023
Cellular
senescence,
a
state
of
irreversible
cell-cycle
arrest
caused
by
variety
cellular
stresses,
is
critically
involved
in
age-related
tissue
dysfunction
various
organs.
However,
the
features
cells
central
nervous
system
that
undergo
senescence
and
their
role
neural
impairment
are
not
well
understood
as
yet.
Here,
through
comprehensive
investigations
utilising
single-cell
transcriptome
analysis
mouse
models,
we
show
microglia,
particularly
white
matter,
brain
spinal
cord
during
ageing
disease
models
involving
demyelination.
Microglial
predominantly
detected
disease-associated
which
appear
neurodegenerative
diseases.
We
also
find
commensal
bacteria
promote
accumulation
senescent
microglia
ageing.
Furthermore,
knockout
p16INK4a,
key
inducer,
ameliorates
neuroinflammatory
phenotype
damaged
cords
mice.
These
results
advance
our
understanding
open
up
possibilities
for
treatment
disorders.
Translational Neurodegeneration,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: Jan. 23, 2024
Abstract
Ageing
is
a
crucial
risk
factor
for
Alzheimer’s
disease
(AD)
and
characterised
by
systemic
changes
in
both
intracellular
extracellular
microenvironments
that
affect
the
entire
body
instead
of
single
organ.
Understanding
specific
mechanisms
underlying
role
ageing
development
can
facilitate
treatment
ageing-related
diseases,
such
as
AD.
Signs
brain
have
been
observed
AD
patients
animal
models.
Alleviating
pathological
caused
dramatically
ameliorate
amyloid
beta-
tau-induced
neuropathological
memory
impairments,
indicating
plays
pathophysiological
process
In
this
review,
we
summarize
impact
several
age-related
factors
on
propose
preventing
promising
strategy
improving
cognitive
health.
Archives of Toxicology,
Journal Year:
2024,
Volume and Issue:
98(8), P. 2393 - 2408
Published: May 15, 2024
Increasing
evidence
has
revealed
that
cellular
senescence
drives
NDs,
including
Alzheimer's
disease
(AD)
and
Parkinson's
disease.
Different
senescent
cell
populations
secrete
senescence-associated
secretory
phenotypes
(SASP),
matrix
metalloproteinase-3,
interleukin
(IL)-1α,
IL-6,
IL-8,
which
can
harm
adjacent
microglia.
Moreover,
these
cells
possess
high
expression
levels
of
hallmarks
(p16
p21)
elevated
β-galactosidase
activity
in
vitro
vivo
ND
models.
These
contribute
to
the
deposition
β-amyloid
tau-protein
tangles.
Selective
clearance
SASP
regulation
by
inhibiting
p38/mitogen-activated
protein
kinase
nuclear
factor
kappa
B
signaling
attenuate
load
prevent
tangle
deposition,
thereby
improving
cognitive
performance
AD
mouse
In
addition,
telomere
shortening,
a
biomarker,
is
associated
with
increased
risks.
Telomere
dysfunction
causes
senescence,
stimulating
tumor
necrosis
factor-α,
IL-1β
secretions.
The
forced
telomerase
activators
prevents
yielding
considerable
neuroprotective
effects.
This
review
elucidates
mechanism
pathogenesis,
suggesting
strategies
eliminate
or
restore
normal
phenotype
for
treating
such
diseases.
