Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
52(6), P. 2865 - 2885
Published: March 12, 2024
Abstract
A
comprehensive
understanding
of
molecular
changes
during
brain
aging
is
essential
to
mitigate
cognitive
decline
and
delay
neurodegenerative
diseases.
The
interpretation
mRNA
alterations
influenced
by
the
health
age
animal
cohorts
studied.
Here,
we
carefully
consider
these
factors
provide
an
in-depth
investigation
splicing
dynamics
in
mouse
brain,
combining
short-
long-read
sequencing
technologies
with
extensive
bioinformatic
analyses.
Our
findings
encompass
a
spectrum
age-related
changes,
including
differences
isoform
usage,
decreased
module
showing
increased
expression
neuronal
genes.
Notably,
our
results
indicate
reduced
abundance
isoforms
leading
nonsense-mediated
RNA
decay
suggest
regulatory
role
for
RNA-binding
proteins,
indicating
that
their
regulation
may
be
altered
reshaping
aged
transcriptome.
Collectively,
study
highlights
importance
studying
events
aging.
Molecular Metabolism,
Journal Year:
2023,
Volume and Issue:
74, P. 101755 - 101755
Published: June 16, 2023
Recently,
the
hallmarks
of
aging
were
updated
to
include
dysbiosis,
disabled
macroautophagy,
and
chronic
inflammation.
In
particular,
low-grade
inflammation
during
aging,
without
overt
infection,
is
defined
as
"inflammaging,"
which
associated
with
increased
morbidity
mortality
in
population.
Emerging
evidence
suggests
a
bidirectional
cyclical
relationship
between
development
age-related
conditions,
such
cardiovascular
diseases,
neurodegeneration,
cancer,
frailty.
How
crosstalk
other
underlies
biological
mechanisms
disease
thus
particular
interest
current
geroscience
research.
Neurobiology of Disease,
Journal Year:
2024,
Volume and Issue:
196, P. 106505 - 106505
Published: April 19, 2024
Alzheimer's
and
Parkinson's
diseases
are
two
of
the
most
frequent
neurological
diseases.
The
clinical
features
AD
memory
decline
cognitive
dysfunction,
while
PD
mainly
manifests
as
motor
dysfunction
such
limb
tremors,
muscle
rigidity
abnormalities,
slow
gait.
Abnormalities
in
cholesterol,
sphingolipid,
glycerophospholipid
metabolism
have
been
demonstrated
to
directly
exacerbate
progression
by
stimulating
Aβ
deposition
tau
protein
tangles.
Indirectly,
abnormal
lipids
can
increase
burden
on
brain
vasculature,
induce
insulin
resistance,
affect
structure
neuronal
cell
membranes.
Abnormal
lipid
leads
through
inducing
accumulation
α-syn,
mitochondria
endoplasmic
reticulum,
ferroptosis.
Great
progress
has
made
targeting
abnormalities
for
treatment
recent
years,
like
metformin,
insulin,
peroxisome
proliferator-activated
receptors
(PPARs)
agonists,
monoclonal
antibodies
apolipoprotein
E
(ApoE).
This
review
comprehensively
summarizes
involvement
dysregulated
pathogenesis
PD,
application
Lipid
Monitoring,
emerging
regulatory
drug
targets.
A
better
understanding
lipidological
bases
may
pave
way
developing
effective
prevention
methods
neurodegenerative
disorders.
Journal of Ovarian Research,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: May 31, 2024
Abstract
In
women
who
are
getting
older,
the
quantity
and
quality
of
their
follicles
or
oocytes
decline.
This
is
characterized
by
decreased
ovarian
reserve
function
(DOR),
fewer
remaining
oocytes,
lower
oocytes.
As
more
choose
to
delay
childbirth,
decline
in
fertility
associated
with
age
has
become
a
significant
concern
for
modern
women.
The
oocyte
key
indicator
aging.
Many
studies
suggest
that
age-related
changes
energy
metabolism
may
impact
quality.
Changes
affect
adenosine
5'-triphosphate
(ATP)
production,
but
how
related
products
proteins
influence
remains
largely
unknown.
review
focuses
on
aging
its
potential
quality,
as
well
therapeutic
strategies
partially
metabolism.
research
aims
enhance
our
understanding
metabolism,
identification
biomarkers
treatment
methods.
Journal of Translational Medicine,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Jan. 6, 2025
The
activation
of
macrophages
or
microglia
in
patients'
whole
body
local
eyes
play
significant
roles
diabetic
retinopathy
(DR).
Mitochondrial
function
regulates
the
inflammatory
polarization
macrophages.
Therefore,
common
mechanism
mitochondrial
related
genes
(MRGs)
and
macrophage
polarisation
(MPRGs)
DR
is
explored
our
study
to
illustrate
pathophysiology
DR.
In
this
study,
using
transcriptome
data,
differentially
expressed
(DEGs)
were
firstly
analysed
for
GSE221521,
while
module
MPRGs
obtained
by
weighted
gene
co-expression
network
analysis
(WGCNA),
intersections
DEGs
with
MRGs
taken,
taken.
After
that,
correlation
analyses
performed
obtain
candidate
genes.
Key
Mendelian
randomisation
(MR)
analysis,
then
biomarkers
machine
learning
combined
receiver
operating
characteristic
(ROC)
expression
validation
between
control
cohorts
GSE221521
GSE160306
biomarkers.
Finally,
subjected
immune
infiltration
set
enrichment
(GSEA),
gene–gene
interaction
(GGI)
analysis.
A
number
784
taken
intersect
1136
782
MPRGs,
respectively,
after
which
89
as
MR
yielded
13
key
clear
causal
links
trends
PTAR1
SLC25A34
consistent
notable
cohort
GSE160306.
So
used
Immune
showed
that
activated
NK
cell
Monocyte
notably
different
cohorts,
strongest
positive
correlations
cell.
Both
enriched
lysosome
insulin
signaling
pathway.
GGI
associated
prenyltransferase
activity
prenylation
function.
This
identified
two
(PTAR1
SLC25A34)
explore
pathogenesis
provide
reference
targets
drug
development.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
175, P. 116689 - 116689
Published: May 3, 2024
Ischemic
heart
disease
invariably
leads
to
devastating
damage
human
health.
Nicotinamide
ribose
(NR),
as
one
of
the
precursors
NAD+
synthesis,
has
been
discovered
exert
a
protective
role
in
various
neurological
and
cardiovascular
disorders.
Our
findings
demonstrated
that
pretreatment
with
200
mg/kg
NR
for
3
h
significantly
reduced
myocardial
infarct
area,
decreased
levels
CK-MB
LDH
serum,
improved
cardiac
function
rats
during
ischemia-reperfusion
(I/R)
injury.
Meanwhile,
0.5
mM
also
effectively
increased
viability
release
H9c2
cells
OGD/R.
We
had
provided
evidence
could
decrease
mitochondrial
reactive
oxygen
species
(mtROS)
production
MDA
content,
enhance
SOD
activity,
thereby
mitigating
inhibiting
apoptosis
I/R
Further
investigations
revealed
content
upregulated
SIRT3
protein
expression
myocardium.
Through
using
small
interfering
RNA
deacetylase
activity
inhibitor
3-TYP,
we
confirmed
cardioprotective
effect
on
cardiomyocytes
was
largely
dependent
inhibition
oxidative
stress
via
SIRT3-SOD2
axis.
Overall,
our
study
suggested
exogenous
supplementation
mitigated
inhibited
injury
by
reducing
SIRT3-SOD2-mtROS
pathway.
Molecular Therapy,
Journal Year:
2024,
Volume and Issue:
32(6), P. 1760 - 1778
Published: April 24, 2024
Glaucoma
is
characterized
by
the
progressive
degeneration
of
retinal
ganglion
cells
(RGCs)
and
their
axons,
its
risk
increases
with
aging.
Yet
comprehensive
insights
into
complex
mechanisms
are
largely
unknown.
Here,
we
found
that
anti-aging
molecule
Sirt6
was
highly
expressed
in
RGCs.
Deleting
globally
or
specifically
RGCs
led
to
RGC
loss
optic
nerve
during
aging,
despite
normal
intraocular
pressure
(IOP),
resembling
a
phenotype
normal-tension
glaucoma.
These
detrimental
effects
were
potentially
mediated
accelerated
senescence
through
Caveolin-1
upregulation
induction
mitochondrial
dysfunction.
In
mouse
models
high-tension
glaucoma,
level
decreased
after
IOP
elevation.
Genetic
overexpression
significantly
attenuated
high
tension-induced
whereas
partial
RGC-specific
deletion
loss.
Importantly,
therapeutically
targeting
pharmacological
activator
AAV2-mediated
gene
delivery
ameliorated
IOP-induced
degeneration.
Together,
our
studies
reveal
critical
role
preventing
aging
setting
stage
for
further
exploration
activation
as
potential
therapy
Medicinal Research Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 31, 2024
Abstract
The
sirtuin
family
comprises
seven
NAD
+
‐dependent
enzymes
which
catalyze
protein
lysine
deacylation
and
mono
ADP‐ribosylation.
Sirtuins
act
as
central
regulators
of
genomic
stability
gene
expression
control
key
processes,
including
energetic
metabolism,
cell
cycle,
differentiation,
apoptosis,
aging.
As
a
result,
all
sirtuins
play
critical
roles
in
cellular
homeostasis
organism
wellness,
their
dysregulation
has
been
linked
to
metabolic,
cardiovascular,
neurological
diseases.
Furthermore,
have
shown
dichotomous
cancer,
acting
context‐dependent
tumor
suppressors
or
promoters.
Given
role
different
attracted
increasing
research
interest
aimed
at
developing
both
activators
inhibitors.
Indeed,
modulation
may
therapeutic
effects
many
age‐related
diseases,
diabetes,
cardiovascular
neurodegenerative
disorders,
cancer.
Moreover,
isoform
selective
modulators
increase
our
knowledge
biology
aid
develop
better
therapies.
Through
this
review,
we
provide
insights
into
pharmacology
illustrate
enzymatic
activities
biological
functions.
outline
the
most
relevant
terms
modes
action,
structure–activity
relationships,
pharmacological
effects,
clinical
applications.
Biological Trace Element Research,
Journal Year:
2024,
Volume and Issue:
202(12), P. 5395 - 5412
Published: Feb. 28, 2024
The
formation
of
the
central
nervous
system
is
a
meticulously
planned
and
intricate
process.
Any
modification
to
this
process
has
potential
disrupt
structure
operation
brain,
which
could
result
in
deficiencies
neurological
growth.
When
neurotoxic
substances
are
present
during
early
stages
development,
they
can
be
exceptionally
dangerous.
Prenatally,
immature
brain
extremely
vulnerable
therefore
at
high
risk
pregnant
women
associated
with
occupational
exposures.
Lead,
fluoride,
aluminum,
cadmium
examples
possibly
toxic
trace
elements
that
have
been
identified
as
an
environmental
concern
aetiology
number
neurodegenerative
illnesses.
SIRT1,
member
sirtuin
family
received
most
attention
for
its
neuroprotective
properties.
SIRT1
intriguing
therapeutic
target
since
it
demonstrates
important
functions
increase
neurogenesis
cellular
lifespan
by
modulating
multiple
pathways.
It
promotes
axonal
extension,
neurite
growth,
dendritic
branching
development
neurons.
Additionally,
contributes
neurogenesis,
synaptic
plasticity,
memory
neuroprotection.
This
review
summarizes
possible
role
signalling
pathway
potentially
-induced
neurodevelopmental
toxicity,
highlighting
some
molecular
pathways
such
mitochondrial
biogenesis,
CREB/BDNF
PGC-1α/NRF1/TFAM.