Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization
Journal of Cachexia Sarcopenia and Muscle,
Год журнала:
2024,
Номер
15(3), С. 1121 - 1133
Опубликована: Март 31, 2024
Abstract
Background
Cytokines
and
growth
factors
may
serve
as
a
bridge
in
studying
the
causal
relationships
between
inflammaging
sarcopenia
due
to
their
roles
inflammaging.
In
this
study,
we
aim
explore
association
of
cytokines
with
aging
traits
further
identify
significant
inflammation
factors.
Methods
Bidirectional
Mendelian
randomization
(MR)
analysis
was
used
causality.
Forty‐one
kinds
circulation
were
set
exposures,
data
from
summary
genome‐wide
study
(GWAS)
containing
three
cohorts
8293
healthy
participants
European
ancestry
1983
2011.
Hand
grip
strength,
adjusted
appendicular
lean
mass
(AALM),
usual
walking
pace,
moderate‐to‐vigorous
physical
activity
(MVPA)
levels,
able
walk
or
cycle
unaided
for
10
min
(AWCU10)
telomere
length
selected
outcomes.
Data
outcomes
obtained
meta‐GWAS
UK
Biobank,
sample
sizes
ranged
69
537
472
174.
Low
hand
strength
defined
by
Working
Group
on
Sarcopenia
Older
People
(EWGSOP)
Foundation
National
Institutes
Health
(FNIH)
cut‐off
points,
respectively.
Other
outcome
measured
according
Biobank
raw
cohorts'
criteria.
We
two
significance
thresholds
single
nucleotide
polymorphisms
(SNPs)
associated
exposures
obtain
adequate
SNPs
(5
×
−6
5
−8
).
Inverse‐variance
weighted,
MR‐Egger
weighted
median
employed
estimate
Results
Twenty‐seven
identified
relate
causally,
most
only
one
trait.
IL16
(interleukin‐16),
CTACK
(cutaneous
T‐cell
attracting
chemokine),
MIP1b
(macrophage
inflammatory
protein
1b)
PDGFbb
(platelet‐derived
factor
BB)
proven
causally
at
least
trait
both
analyses
thresholds.
(0.977
[0.956–0.998]
EWGSOP
0.933
[0.874–0.996]
FNIH),
AALM
(0.991
[0.984,
0.998]),
MVPA
(0.997
[0.995–1.000])
AWCU10
(1.008
[1.003–1.013]).
(1.013
[1.007–1.019]
1.090
[1.041–1.142]
(0.990
[0.986–0.994])
(0.998
[0.983–0.994]).
The
results
indicated
that
has
effect
(1.032
[1.001–1.063]
EWGSOP),
(0.994
[0.988–1.000]
0.993
[0.988–0.998])
(1.006
[1.000–1.012]).
(1.016
[1.001–1.030])
(1.011
[1.007–1.015]).
Reserve
MR
also
proved
unidirectional
effects.
Conclusions
related
traits,
effects
IL16,
CTACK,
Язык: Английский
Obstructive sleep apnea’s causal links to depression, well-being, and negative moods: a bidirectional mendelian randomized study
European Archives of Psychiatry and Clinical Neuroscience,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 2, 2025
Язык: Английский
Causal Associations of Inflammatory Cytokines With Osteosarcopenia: Insights From Mendelian Randomization and Single Cell Analysis
Mediators of Inflammation,
Год журнала:
2025,
Номер
2025(1)
Опубликована: Янв. 1, 2025
Background:
Osteosarcopenia,
the
coexistence
of
osteoporosis
and
sarcopenia,
poses
significant
challenges
in
aging
populations
due
to
its
dual
impact
on
bone
muscle
health.
Inflammation,
mediated
by
specific
cytokines,
is
thought
play
a
crucial
role
development
osteosarcopenia,
though
underlying
mechanisms
are
not
fully
understood.
Objective:
This
study
aimed
clarify
causal
circulating
cytokines
pathogenesis
osteosarcopenia
employing
mendelian
randomization
(MR)
single-cell
RNA
sequencing
(scRNA-seq)
identify
cell-specific
cytokine
expression
patterns.
The
ultimate
objective
was
uncover
potential
pathological
therapeutic
targets
for
treating
osteosarcopenia.
Methods:
A
two-sample
MR
approach
employed,
leveraging
publicly
available
genome-wide
association
(GWAS)
data
from
multiple
cohorts.
total
91
were
examined
using
genetic
instruments,
their
effects
traits
related
sarcopenia
evaluated.
Various
complementary
sensitivity
analyses
performed
ensure
robust
findings.
Additionally,
scRNA-seq
datasets
human
marrow
analyzed
validate
profiles
candidate
cytokines.
Results:
analysis
identified
several
with
traits,
including
LTA,
CD40,
CXCL6,
CXCL10,
DNER
(delta
notch-like
epidermal
growth
factor-related
receptor),
VEGFA
(vascular
endothelial
factor
A).
LTA
CD40
protective
both
muscle,
while
posed
risk.
Other
demonstrated
opposite
muscle.
Single
cell
revealed
distinct
patterns,
highly
expressed
lymphocytes,
immune
cells,
various
musculoskeletal
types.
Age-related
differences
also
noted,
more
younger
individuals,
older
individuals.
Conclusion:
offers
preliminary
insights
into
inflammatory
potentially
driving
identifying
key
that
may
be
involved
pathogenesis.
By
integrating
data,
we
highlight
targets,
further
research
needed
confirm
these
findings
implications
Язык: Английский
Role of IL-16 in age-related skeletal muscle atrophy: an integrated study
BMC Musculoskeletal Disorders,
Год журнала:
2025,
Номер
26(1)
Опубликована: Апрель 17, 2025
In
this
study,
we
aim
to
explore
the
roles
of
IL-16
in
sarcopenia
based
on
older
orthopedic
patients
and
animal
research.
This
clinical
research
study
was
an
observational
investigation
included
all
with
trauma
admitted
our
department
between
January
2021
2022.
Patients
were
identified
if
they
have
both
low
hand
grip
strength
(HGS)
appendicular
skeletal
muscle
mass
(ASM).
Propensity
score
matching
(PSM)
performed
reduce
bias
caused
by
co-factors
levels
normal
compared.
research,
mice
treated
identify
effects
function
mass.
Then
models
established
anti-IL-16
potential
therapeutical
effect
targeting
IL-16.
421
individuals
77
as
sarcopenia.
matched
populations,
serum
HGS,
ASM,
significantly
higher
than
(all
p
<
0.001).
The
showed
impaired
physical
performance
loss
Using
antibodies
may
rescue
traits
botulinum
toxin
type
A.
Individuals
high
a
risk
impairs
leads
atrophy
mice,
these
could
be
reduced
Язык: Английский
Molecular Mechanisms and Potential Interventions During Aging-associated Sarcopenia
Mechanisms of Ageing and Development,
Год журнала:
2024,
Номер
unknown, С. 112020 - 112020
Опубликована: Дек. 1, 2024
Язык: Английский
Sarcopenia and immune-mediated inflammatory diseases: Evaluating causality and exploring therapeutic targets for sarcopenia through Mendelian randomization
International Immunopharmacology,
Год журнала:
2024,
Номер
144, С. 113687 - 113687
Опубликована: Ноя. 26, 2024
Язык: Английский
Comprehensive landscapes of the causal network between immunity and sarcopenia
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Авг. 20, 2024
Background
Inflammaging,
an
immune
status
characterized
by
a
sustained
increase
in
pro-inflammatory
markers
and
decline
anti-inflammatory
mechanisms,
is
critical
risk
factor
the
development
of
sarcopenia.
Landscapes
causal
relationships
between
immunity
sarcopenia
are
needed
to
understand
mechanism
provide
novel
treatments
comprehensively.
Methods
We
used
Mendelian
Randomization
(MR)
as
basic
method
this
study.
By
setting
proteins,
cells,
exposures
outcomes
alternatively,
then
combining
them
different
directions,
we
potentially
estimated
their
directions
subsequently
mapped
comprehensive
landscape
based
on
information
efficiently.
To
further
network,
developed
rank-sums
integrate
multiple
algorithms
identify
key
cells
proteins.
Results
More
than
1,000
were
identified
cell
phenotypes,
traits
(p
<
0.05),
maps
these
linkages
established.
In
threshold
FDR
0.05,
hundreds
still
significant.
The
final
map
included
13
phenotypes
8
star
factors
EM
CD8br
%CD8br,
DN
(CD4-
CD8-)
%DN,
SIRT2,
so
on.
Conclusion
reading
landscapes
study,
may
not
only
find
pathways
that
have
been
reported
proven
but
also
proteins
with
enriched
upstream
downstream
pathways.
Язык: Английский
Causal Associations with Arterial Stiffness and Sarcopenia: A Mendelian Randomization Analysis
Rejuvenation Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 26, 2024
Observational
studies
and
clinical
trials
indicate
a
link
between
arterial
stiffness
(AS)
sarcopenia
(SAR),
yet
the
causal
relationship
these
remains
unclear.
The
study
aims
to
investigate
connection
from
AS
SAR
by
Mendelian
randomization
(MR).
We
analyzed
Genome-Wide
Association
Studies
data
for
indicators:
pulse
wave
index
(PWASI)
peak-to-peak
time
(PPT),
low
hand
grip
strength
(LHGS),
usual
walking
pace
(UWP),
moderate-to-vigorous
physical
activity
levels
(MVPA),
walk
or
cycle
unassisted
10
minutes.
inverse
variance-weighted,
MR-Egger,
weighted
mode,
median
were
applied
MR.
There
is
bidirectional
SAR.
PWASI
has
causation
with
UWP
(odds
ratio
[OR]
=
0.97,
95%
confidence
interval
[CI]
0.94-0.99).
PPT
association
MVPA
(OR
1.08,
CI
1.002-1.144)
1.05,
1.017-1.096).
LHGS
causally
associated
0.95,
0.91-0.98)
0.77,
0.65-0.90)
1.37,
1.17-1.60).
increased
could
reduce
motor
ability
slightly
lower
upper
limb
lead
higher
AS.
This
of
two
may
offer
novel
perspectives
advancing
understanding
underlying
mechanisms
related
muscle
pathophysiology.
Язык: Английский