Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 10, 2025
Abstract
In
the
context
of
global
ageing,
prevalence
neurodegenerative
diseases
and
dementia,
such
as
Alzheimer’s
disease
(AD),
is
increasing.
However,
current
symptomatic
disease-modifying
therapies
have
achieved
limited
benefits
for
in
clinical
settings.
Halting
progress
neurodegeneration
cognitive
decline
or
even
improving
impaired
cognition
function
are
clinically
meaningful
goals
treatments
diseases.
Ageing
primary
risk
factor
their
associated
comorbidities,
vascular
pathologies,
elderly
individuals.
Thus,
we
aim
to
elucidate
role
ageing
from
perspective
a
complex
system,
which
brain
core
peripheral
organs
tissues
form
holistic
network
support
functions.
During
progressive
deterioration
structure
entire
body
hampers
its
active
adaptive
responses
various
stimuli,
thereby
rendering
individuals
more
vulnerable
Consequently,
propose
that
prevention
treatment
should
be
grounded
antiageing
rejuvenation
means
complemented
by
interventions
targeting
disease-specific
pathogenic
events.
This
integrated
approach
promising
strategy
effectively
prevent,
pause
slow
down
progression
Science,
Год журнала:
2022,
Номер
376(6598), С. 1192 - 1202
Опубликована: Май 5, 2022
Caloric
restriction
(CR)
prolongs
life
span,
yet
the
mechanisms
by
which
it
does
so
remain
poorly
understood.
Under
CR,
mice
self-impose
chronic
cycles
of
2-hour
feeding
and
22-hour
fasting,
raising
question
if
is
calories,
or
time
day
that
cause
this
increased
span.
We
show
here
30%
CR
was
sufficient
to
extend
span
10%;
however,
a
daily
fasting
interval
circadian
alignment
acted
together
35%
in
male
C57BL/6J
mice.
These
effects
were
independent
body
weight.
Aging
induced
widespread
increases
gene
expression
associated
with
inflammation
decreases
genes
encoding
components
metabolic
pathways
liver
from
ad
libitum-fed
at
night
ameliorated
these
aging-related
changes.
Our
results
interventions
promote
longevity
provide
perspective
further
explore
aging.
Cell,
Год журнала:
2022,
Номер
185(9), С. 1455 - 1470
Опубликована: Апрель 1, 2022
Diet
as
a
whole,
encompassing
food
composition,
calorie
intake,
and
the
length
frequency
of
fasting
periods,
affects
time
span
in
which
health
functional
capacity
are
maintained.
Here,
we
analyze
aging
nutrition
studies
simple
organisms,
rodents,
monkeys,
humans
to
link
longevity
conserved
growth
metabolic
pathways
outline
their
role
age-related
disease.
We
focus
on
feasible
nutritional
strategies
shown
delay
and/or
prevent
diseases
through
epidemiological,
model
organism,
clinical,
centenarian
underline
need
avoid
malnourishment
frailty.
These
findings
integrated
define
diet
based
multi-pillar
approach
adjusted
for
age
status
optimize
lifespan
healthspan
humans.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Июль 23, 2022
Nutriments
have
been
deemed
to
impact
all
physiopathologic
processes.
Recent
evidences
in
molecular
medicine
and
clinical
trials
demonstrated
that
adequate
nutrition
treatments
are
the
golden
criterion
for
extending
healthspan
delaying
ageing
various
species
such
as
yeast,
drosophila,
rodent,
primate
human.
It
emerges
develop
precision-nutrition
therapeutics
slow
age-related
biological
processes
treat
diverse
diseases.
However,
nutritive
advantages
frequently
diversify
among
individuals
well
organs
tissues,
which
brings
challenges
this
field.
In
review,
we
summarize
different
forms
of
dietary
interventions
extensively
prescribed
improvement
disease
treatment
pre-clinical
or
clinical.
We
discuss
nutrient-mediated
mechanisms
including
metabolic
regulators,
metabolism
pathways,
epigenetic
circadian
clocks.
Comparably,
describe
diet-responsive
effectors
by
influence
endocrinic,
immunological,
microbial
neural
states
responsible
improving
health
preventing
multiple
diseases
humans.
Furthermore,
expatiate
patterns
dietotheroapies,
fasting,
calorie-restricted
diet,
ketogenic
high-fibre
plants-based
protein
restriction
diet
with
specific
reduction
amino
acids
microelements,
potentially
affecting
morbid
states.
Altogether,
emphasize
profound
nutritional
therapy,
highlight
crosstalk
explored
critical
factors
individualized
therapeutic
approaches
predictors.
Cell Reports,
Год журнала:
2023,
Номер
42(1), С. 111982 - 111982
Опубликована: Янв. 1, 2023
Cellular
circadian
clocks
direct
a
daily
transcriptional
program
that
supports
homeostasis
and
resilience.
Emerging
evidence
has
demonstrated
age-associated
changes
in
functions.
To
define
age-dependent
at
the
systems
level,
we
profile
transcriptome
hypothalamus,
lung,
heart,
kidney,
skeletal
muscle,
adrenal
gland
three
age
groups.
We
find
tissue-specific
clock
output
changes.
Aging
reduces
number
of
rhythmically
expressed
genes
(REGs),
indicative
weakened
control.
REGs
are
enriched
for
hallmarks
aging,
adding
another
dimension
to
our
understanding
aging.
Analyzing
differential
gene
expression
within
tissue
four
different
times
day
identifies
distinct
clusters
differentially
(DEGs).
Increased
variability
across
is
common
feature
aged
tissues.
This
analysis
extends
landscape
aging
highlights
impact
on
function
temporal
expression.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Март 14, 2023
Abstract
The
ageing
process
is
a
systemic
decline
from
cellular
dysfunction
to
organ
degeneration,
with
more
predisposition
deteriorated
disorders.
Rejuvenation
refers
giving
aged
cells
or
organisms
youthful
characteristics
through
various
techniques,
such
as
reprogramming
and
epigenetic
regulation.
great
leaps
in
rejuvenation
prove
that
not
one-way
street,
many
rejuvenative
interventions
have
emerged
delay
even
reverse
the
process.
Defining
mechanism
by
which
roadblocks
signaling
inputs
influence
complex
programs
essential
for
understanding
developing
strategies.
Here,
we
discuss
intrinsic
extrinsic
factors
counteract
cell
rejuvenation,
targeted
core
mechanisms
involved
this
Then,
critically
summarize
latest
advances
state-of-art
strategies
of
rejuvenation.
Various
methods
also
provide
insights
treating
specific
ageing-related
diseases,
including
reprogramming,
removal
senescence
(SCs)
suppression
senescence-associated
secretory
phenotype
(SASP),
metabolic
manipulation,
stem
cells-associated
therapy,
dietary
restriction,
immune
heterochronic
transplantation,
etc.
potential
applications
therapy
extend
cancer
treatment.
Finally,
analyze
detail
therapeutic
opportunities
challenges
technology.
Deciphering
will
further
into
anti-ageing
disease
treatment
clinical
settings.
Cell Metabolism,
Год журнала:
2023,
Номер
35(1), С. 150 - 165.e4
Опубликована: Янв. 1, 2023
Time-restricted
feeding
(TRF)
is
an
emerging
behavioral
nutrition
intervention
that
involves
a
daily
cycle
of
and
fasting.
In
both
animals
humans,
TRF
has
pleiotropic
health
benefits
arise
from
multiple
organ
systems,
yet
the
molecular
basis
TRF-mediated
not
well
understood.
Here,
we
subjected
mice
to
isocaloric
ad
libitum
(ALF)
or
western
diet
examined
gene
expression
changes
in
samples
taken
22
organs
brain
regions
collected
every
2
h
over
24-h
period.
We
discovered
profoundly
impacts
expression.
Nearly
80%
all
genes
show
differential
rhythmicity
under
at
least
one
tissue.
Functional
annotation
these
revealed
tissue-
pathway-specific
TRF.
These
findings
resources
provide
critical
foundation
for
future
mechanistic
studies
will
help
guide
human
time-restricted
eating
(TRE)
interventions
treat
various
disease
conditions
with
without
pharmacotherapies.
Nature Cell Biology,
Год журнала:
2024,
Номер
26(9), С. 1571 - 1584
Опубликована: Авг. 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.
Cell Metabolism,
Год журнала:
2024,
Номер
36(6), С. 1371 - 1393.e7
Опубликована: Май 7, 2024
The
role
and
molecular
mechanisms
of
intermittent
fasting
(IF)
in
non-alcoholic
steatohepatitis
(NASH)
its
transition
to
hepatocellular
carcinoma
(HCC)
are
unknown.
Here,
we
identified
that
an
IF
5:2
regimen
prevents
NASH
development
as
well
ameliorates
established
fibrosis
without
affecting
total
calorie
intake.
Furthermore,
the
blunted
NASH-HCC
when
applied
therapeutically.
timing,
length,
number
cycles
type
diet
were
critical
parameters
determining
benefits
fasting.
Combined
proteome,
transcriptome,
metabolome
analyses
peroxisome-proliferator-activated
receptor
alpha
(PPARα)
glucocorticoid-signaling-induced
PCK1
act
co-operatively
hepatic
executors
response.
In
line
with
this,
PPARα
targets
reduced
human
NASH.
Notably,
only
initiated
during
active
phase
mice
robustly
induced
glucocorticoid
signaling
free-fatty-acid-induced
signaling.
However,
hepatocyte-specific
deletion
partially
abrogated
contrast,
combined
knockdown
Ppara
Pck1
vivo
abolished
beneficial
outcomes
against
inflammation
fibrosis.
Moreover,
overexpression
alone
or
together
lowered
triglycerides
steatosis.
Our
data
support
notion
is
a
promising
intervention
subsequent
liver
cancer.