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.
Circulation Research,
Год журнала:
2020,
Номер
126(11), С. 1549 - 1564
Опубликована: Май 21, 2020
Obesity
is
becoming
an
epidemic
in
the
United
States
and
worldwide
increases
risk
for
many
diseases,
particularly
insulin
resistance,
type
2
diabetes
mellitus,
cardiovascular
disease.
The
mechanisms
linking
obesity
with
these
diseases
remain
incompletely
understood.
Over
past
to
3
decades,
it
has
been
recognized
that
obesity,
inflammation,
increased
accumulation
inflammatory
polarization
of
immune
cells,
takes
place
various
tissues,
including
adipose
tissue,
skeletal
muscle,
liver,
gut,
pancreatic
islet,
brain
may
contribute
obesity-linked
metabolic
dysfunctions,
leading
resistance
mellitus.
Therapies
targeting
inflammation
have
shed
light
on
certain
mellitus
atherosclerotic
disease,
but
be
tested
further
confirmed
clinical
trials.
This
review
focuses
tissue
its
potential
role
associated
obesity.
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.
Limited
experimental
evidence
bridges
nutrition
and
cancer
immunosurveillance.
Here,
we
show
that
ketogenic
diet
(KD)
-
or
its
principal
ketone
body,
3-hydroxybutyrate
(3HB),
most
specifically
in
intermittent
scheduling
induced
T
cell-dependent
tumor
growth
retardation
of
aggressive
models.
In
conditions
which
anti-PD-1
alone
combination
with
anti-CTLA-4
failed
to
reduce
mice
receiving
a
standard
diet,
KD,
oral
supplementation
3HB
reestablished
therapeutic
responses.
Supplementation
KD
sucrose
(which
breaks
ketogenesis,
abolishing
production)
pharmacological
antagonist
the
receptor
GPR109A
abolished
antitumor
effects.
Mechanistically,
prevented
immune
checkpoint
blockade-linked
upregulation
PD-L1
on
myeloid
cells,
while
favoring
expansion
CXCR3+
cells.
compositional
changes
gut
microbiota,
distinct
species
such
as
Eisenbergiella
massiliensis
commonly
emerging
humans
subjected
carbohydrate-low
interventions
highly
correlating
serum
concentrations
3HB.
Altogether,
these
results
demonstrate
induces
3HB-mediated
antineoplastic
effect
relies
cell-mediated
Summary
Nonalcoholic
fatty
liver
disease
(NAFLD)
is
a
major
cause
of
chronic
disease,
characterized
by
hepatic
fat
accumulation
and
possible
development
inflammation,
fibrosis,
cancer.
The
ketogenic
diet
(KD),
with
its
drastic
carbohydrate
reduction,
now
popular
weight
loss
intervention,
despite
safety
concerns
on
association
liver.
However,
KDs
were
also
reported
to
be
beneficial
pathology,
ketone
bodies
recently
proposed
as
effective
modulators
inflammation
fibrosis.
If
the
impact
NAFLD
established,
less
known
effect
macronutrient
distribution
such
outcome.
In
hypocaloric
regimen,
latter
seems
not
crucial,
whereas
at
higher
calorie
intake,
ratio
and,
theoretically,
ketosis,
may
become
important.
could
positively
for
their
very
low
content,
whether
ketosis
plays
an
additional
role
unknown.
Indeed,
several
mechanisms
directly
link
improvement,
elucidating
these
aspects
would
pave
way
new
therapeutic
strategies.
We
herein
aimed
providing
accurate
revision
current
literature
NAFLD,
focusing
clinical
evidence,
metabolic
pathways
involved,
strict
categorization
dietary
interventions.
