Abstract
The
GDF15
protein,
a
member
of
the
TGF-β
superfamily,
is
stress-induced
multifunctional
protein
with
many
its
functions
associated
regulation
immune
system.
signaling
provides
defence
against
excessive
inflammation
induced
by
diverse
stresses
and
tissue
injuries.
Given
that
aging
process
low-grade
inflammatory
state,
called
inflammaging,
it
not
surprising
expression
gradually
increases
aging.
In
fact,
core
factor
secreted
senescent
cells,
state
senescence-associated
secretory
phenotype
(SASP).
Many
age-related
stresses,
e.g.,
mitochondrial
endoplasmic
reticulum
as
well
inflammatory,
metabolic,
oxidative
induce
GDF15.
Although
an
effective
anti-inflammatory
modulator,
there
robust
evidence
pro-aging
promoting
process.
only
modulator
but
also
potent
immunosuppressive
enhancer
in
chronic
states.
can
stimulate
responses
either
non-specifically
via
receptors
superfamily
or
specifically
through
GFRAL/HPA/glucocorticoid
pathway.
stimulates
network
activating
MDSCs,
Tregs,
M2
macrophages
triggering
inhibitory
checkpoint
cells.
Immunosuppressive
suppress
processes
they
evoke
detrimental
effects
aged
tissues,
such
cellular
senescence,
fibrosis,
atrophy/sarcopenia.
It
seems
survival
go
awry
persistent
thus
diseases.
Aging Clinical and Experimental Research,
Год журнала:
2024,
Номер
36(1)
Опубликована: Дек. 3, 2024
Abstract
Background
Growth
differentiation
factor
15
(GDF15)
is
a
crucial
biomarker
in
various
physiological
and
pathological
processes.
While
elevated
GDF15
levels
are
linked
to
increased
mortality
risk,
the
role
of
DNA
methylation
(DNAm)-predicted
predicting
has
not
been
extensively
studied.
The
purpose
study
investigate
association
between
DNAm-predicted
all-cause
cardiovascular
disease
(CVD)
nationally
representative
cohort.
Methods
Data
from
NHANES
1999–2002
were
analyzed.
estimated
using
regression
model.
Weighted
multivariate
Cox
regressions
employed
assess
relationship
outcomes.
Restricted
cubic
splines
used
explore
dose-response
relationships,
subgroup
analyses
conducted
enhance
result
reliability.
Results
Higher
significantly
associated
with
risk
(HR
=
1.08,
95%
CI:
1.02–1.15).
Participants
highest
tertile
showed
higher
1.56,
1.16–2.10)
2.52-fold
2.52,
1.22–5.19).
Kaplan-Meier
curves
revealed
decreasing
survival
probability
tertiles.
spline
analysis
demonstrated
non-linear
mortality.
positive
correlation
remained
robust
most
subgroups.
Conclusions
independently
predicts
This
persists
across
multiple
models
stratified
subgroups,
supporting
GDF15’s
value
as
for
stratification.
Future
research
should
elucidate
underlying
biological
mechanisms
evaluate
clinical
utility
guiding
reduction
interventions.
Abstract
The
GDF15
protein,
a
member
of
the
TGF-β
superfamily,
is
stress-induced
multifunctional
protein
with
many
its
functions
associated
regulation
immune
system.
signaling
provides
defence
against
excessive
inflammation
induced
by
diverse
stresses
and
tissue
injuries.
Given
that
aging
process
low-grade
inflammatory
state,
called
inflammaging,
it
not
surprising
expression
gradually
increases
aging.
In
fact,
core
factor
secreted
senescent
cells,
state
senescence-associated
secretory
phenotype
(SASP).
Many
age-related
stresses,
e.g.,
mitochondrial
endoplasmic
reticulum
as
well
inflammatory,
metabolic,
oxidative
induce
GDF15.
Although
an
effective
anti-inflammatory
modulator,
there
robust
evidence
pro-aging
promoting
process.
only
modulator
but
also
potent
immunosuppressive
enhancer
in
chronic
states.
can
stimulate
responses
either
non-specifically
via
receptors
superfamily
or
specifically
through
GFRAL/HPA/glucocorticoid
pathway.
stimulates
network
activating
MDSCs,
Tregs,
M2
macrophages
triggering
inhibitory
checkpoint
cells.
Immunosuppressive
suppress
processes
they
evoke
detrimental
effects
aged
tissues,
such
cellular
senescence,
fibrosis,
atrophy/sarcopenia.
It
seems
survival
go
awry
persistent
thus
diseases.
