Alzheimer s Research & Therapy,
Journal Year:
2024,
Volume and Issue:
16(1)
Published: Oct. 23, 2024
Blood-derived
mitochondrial
DNA
copy
number
(mtDNA-CN)
is
a
proxy
measurement
of
function
in
the
peripheral
and
central
systems.
Abnormal
mtDNA-CN
not
only
indicates
impaired
mtDNA
replication
transcription
machinery
but
also
dysregulated
biological
processes
such
as
energy
lipid
metabolism.
However,
relationship
between
Alzheimer
disease
(AD)
unclear.
We
performed
two-sample
Mendelian
randomization
(MR)
using
publicly
available
summary
statistics
from
GWAS
for
AD
to
investigate
causal
AD.
estimated
whole-genome
sequence
data
blood
brain
samples
13,799
individuals
Alzheimer's
Disease
Sequencing
Project.
Linear
Cox
proportional
hazards
models
adjusting
age,
sex,
study
phase
were
used
assess
association
with
The
biomarkers
serum
metabolites
was
evaluated
Neuroimaging
Initiative
linear
regression.
conducted
mediation
analysis
test
natural
indirect
effects
change
on
risk
through
significantly
associated
metabolites.
MR
suggested
decreased
blood-derived
increased
(OR
=
0.68;
P
0.013).
Survival
showed
that
higher
conversion
mild
cognitive
impairment
(HR
0.80;
0.002).
identified
significant
associations
FDG-PET
(β
0.103;
0.022),
amyloid-PET
0.117;
0.034),
CSF
amyloid-β
(Aβ)
42/40
(β=-0.124;
0.017),
t-Tau
0.128;
0.015),
p-Tau
0.140;
0.008),
plasma
NFL
0.004)
females.
Several
species,
amino
acids,
biogenic
amines
mtDNA-CN.
Causal
analyses
about
third
effect
mediated
by
(P
0.009),
this
more
females
<
0.005).
Our
measured
predictive
including
particularly
Further,
we
illustrate
possibly
increases
dysregulation
metabolism
inflammation.
Trends in Cell Biology,
Journal Year:
2023,
Volume and Issue:
33(9), P. 788 - 802
Published: March 5, 2023
Autophagy
is
an
intracellular
degradation
pathway
that
recycles
subcellular
components
to
maintain
metabolic
homeostasis.
NAD
essential
metabolite
participates
in
energy
metabolism
and
serves
as
a
substrate
for
series
of
NAD+-consuming
enzymes
(NADases),
including
PARPs
SIRTs.
Declining
levels
autophagic
activity
represent
features
cellular
ageing,
consequently
enhancing
either
significantly
extends
health/lifespan
animals
normalises
cells.
Mechanistically,
it
has
been
shown
NADases
can
directly
regulate
autophagy
mitochondrial
quality
control.
Conversely,
preserve
by
modulating
stress.
In
this
review
we
highlight
the
mechanisms
underlying
bidirectional
relationship
between
autophagy,
potential
therapeutic
targets
provides
combatting
age-related
disease
promoting
longevity.
Nature Cell Biology,
Journal Year:
2024,
Volume and Issue:
26(9), P. 1571 - 1584
Published: Aug. 8, 2024
Abstract
Caloric
restriction
and
intermittent
fasting
prolong
the
lifespan
healthspan
of
model
organisms
improve
human
health.
The
natural
polyamine
spermidine
has
been
similarly
linked
to
autophagy
enhancement,
geroprotection
reduced
incidence
cardiovascular
neurodegenerative
diseases
across
species
borders.
Here,
we
asked
whether
cellular
physiological
consequences
caloric
depend
on
metabolism.
We
report
that
levels
increased
upon
distinct
regimens
or
in
yeast,
flies,
mice
volunteers.
Genetic
pharmacological
blockade
endogenous
synthesis
fasting-induced
nematodes
cells.
Furthermore,
perturbing
pathway
vivo
abrogated
lifespan-
healthspan-extending
effects,
as
well
cardioprotective
anti-arthritic
fasting.
Mechanistically,
mediated
these
effects
via
induction
hypusination
translation
regulator
eIF5A.
In
summary,
polyamine–hypusination
axis
emerges
a
phylogenetically
conserved
metabolic
control
hub
for
fasting-mediated
enhancement
longevity.
Frontiers in Molecular Biosciences,
Journal Year:
2025,
Volume and Issue:
11
Published: Jan. 28, 2025
Aging
and
cancer
are
intricately
linked
through
shared
molecular
processes
that
influence
both
the
onset
of
malignancy
progression
age-related
decline.
As
organisms
age,
cellular
stress,
genomic
instability,
an
accumulation
senescent
cells
create
a
pro-inflammatory
environment
conducive
to
development.
Autophagy,
process
responsible
for
degrading
recycling
damaged
components,
plays
pivotal
role
in
this
relationship.
While
autophagy
acts
as
tumor-suppressive
mechanism
by
preventing
organelles
proteins,
often
exploit
it
survive
under
conditions
metabolic
stress
treatment
resistance.
The
interplay
between
aging,
cancer,
reveals
key
insights
into
tumorigenesis,
senescence,
proteostasis
dysfunction.
This
review
explores
connections
these
processes,
emphasizing
potential
autophagy-targeted
therapies
strategies
could
be
further
explored
aging
treatment.
Understanding
dual
roles
suppressing
promoting
offers
promising
avenues
therapeutic
interventions
aimed
at
improving
outcomes
elderly
patients
while
addressing
deterioration.
The Annual Review of Pharmacology and Toxicology,
Journal Year:
2023,
Volume and Issue:
64(1), P. 339 - 357
Published: Aug. 16, 2023
Rapid
removal
of
apoptotic
cells
by
phagocytes,
a
process
known
as
efferocytosis,
is
key
for
the
maintenance
tissue
homeostasis,
resolution
inflammation,
and
repair.
However,
impaired
efferocytosis
can
result
in
accumulation
cells,
subsequently
triggering
sterile
inflammation
through
release
endogenous
factors
such
DNA
nuclear
proteins
from
membrane
permeabilized
dying
cells.
Here,
we
review
molecular
basis
three
phases
that
is,
detection,
uptake,
degradation
materials
phagocytes.
We
also
discuss
how
defects
due
to
alteration
phagocytes
contribute
low-grade
chronic
occurs
during
aging,
described
inflammaging.
Lastly,
explore
opportunities
targeting
harnessing
efferocytic
machinery
limit
aging-associated
inflammatory
diseases.
Seminars in Cancer Biology,
Journal Year:
2024,
Volume and Issue:
99, P. 24 - 44
Published: Feb. 1, 2024
Autophagy,
a
self-degradative
process
vital
for
cellular
homeostasis,
plays
significant
role
in
adipose
tissue
metabolism
and
tumorigenesis.
This
review
aims
to
elucidate
the
complex
interplay
between
autophagy,
obesity,
cancer
development,
with
specific
emphasis
on
how
obesity-driven
changes
affect
regulation
of
autophagy
subsequent
implications
risk.
The
burgeoning
epidemic
obesity
underscores
relevance
this
research,
particularly
given
established
links
various
cancers.
Our
exploration
delves
into
hormonal
influence,
notably
INS
(insulin)
LEP
(leptin),
interactions.
Further,
we
draw
attention
latest
findings
molecular
factors
linking
cancer,
including
changes,
altered
metabolism,
secretory
autophagy.
We
posit
that
targeting
modulation
may
offer
potent
therapeutic
approach
obesity-associated
pointing
promising
advancements
nanocarrier-based
targeted
therapies
modulation.
However,
also
recognize
challenges
inherent
these
approaches,
concerning
their
precision,
control,
dual
roles
can
play
cancer.
Future
research
directions
include
identifying
novel
biomarkers,
refining
therapies,
harmonizing
approaches
precision
medicine
principles,
thereby
contributing
more
personalized,
effective
treatment
paradigm
obesity-mediated
Neurobiology of Disease,
Journal Year:
2024,
Volume and Issue:
201, P. 106655 - 106655
Published: Aug. 30, 2024
This
study
aims
to
identify
distinct
microbial
and
functional
biomarkers
characteristic
of
body-first
or
brain-first
subtypes
Parkinson's
disease
(PD).
could
illuminate
the
unique
pathogenic
mechanisms
within
these
subtypes.