medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 30, 2024
Abstract
Importance:
Schizophrenia
is
associated
with
increased
age-related
morbidity,
mortality,
and
frailty,
which
are
not
entirely
explained
by
behavioral
factors.
Prior
studies
using
epigenetic
clocks
have
suggested
that
schizophrenia
accelerated
aging,
however
these
primarily
used
unidimensional
summarize
aging
as
a
single
“biological
age”
score.
Objective:
This
meta-analysis
uses
multidimensional
split
into
multiple
scores
to
analyze
biological
in
schizophrenia.
These
novel
may
provide
more
granular
insights
the
mechanistic
relationships
between
schizophrenia,
premature
morbidity
mortality.
Study
selection:
Selected
included
patients
schizophrenia-spectrum
disorders
non-
psychiatric
controls
available
DNA
methylation
data.
Seven
cross-sectional
datasets
were
for
this
study,
total
sample
size
of
1,891
1,881
controls.
Data
extraction
synthesis:
Studies
selected
consensus
Meta-analyses
performed
fixed-effect
models.
Main
outcomes
measures:
We
analyzed
clocks,
including
causality-
enriched
CausAge
physiological
system-specific
SystemsAge
RetroelementAge,
DNAmEMRAge,
multi
omics-informed
OMICmAge.
examined
clock
associations
disease
status
clozapine
use,
after
accounting
age
sex.
Results:
Overall
SystemsAge,
CausAge,
OMICmAge
demonstrated
strict
multiple-comparison
testing.
Ten
eleven
sub-clocks
corresponding
different
systems
strongest
effects
Heart
Lung
followed
Metabolic
Brain
systems.
The
indicated
increases
both
damaging
adaptive
though
weaker
compared
scores.
changes
clinical
biomarkers,
hematologic
hepatic
markers
support
well
proteins
metabolites
previously
linked
Most
acceleration
at
first
psychotic
episode.
Notably,
use
was
Inflammation
partially
be
driven
smoking.
results
survived
Bonferroni
testing
correction.
Conclusions
relevance:
analyses
nuanced
view
identifies
organ
high
risk
schizophrenia-related
disorders.
Abstract
DNA
methylation
is
a
critical
epigenetic
modification
that
regulates
gene
expression
and
plays
significant
role
in
development
disease
processes.
Here,
we
present
the
Cytosine-phosphate-Guanine
Pretrained
Transformer
(CpGPT),
novel
foundation
model
pretrained
on
over
1,500
datasets
encompassing
100,000
samples
from
diverse
tissues
conditions.
CpGPT
leverages
an
improved
transformer
architecture
to
learn
comprehensive
representations
of
patterns,
allowing
it
impute
reconstruct
genome-wide
profiles
limited
input
data.
By
capturing
sequence,
positional,
contexts,
outperforms
specialized
models
when
finetuned
for
aging-related
tasks,
including
chronological
age
prediction,
mortality
risk,
morbidity
assessments.
The
highly
adaptable
across
different
platforms
tissue
types.
Furthermore,
analysis
sample-specific
attention
weights
enables
identification
most
influential
CpG
sites
individual
predictions.
As
model,
sets
new
benchmark
analysis,
achieving
strong
performance
Biomarkers
Aging
Challenge,
where
placed
second
overall
estimation
first
public
leaderboard
methylation-based
prediction.
Highlights
100,000+
samples.
demonstrates
zero-shot
tasks
imputation,
array
conversion,
reference
mapping.
achieves
state-of-the-art
results
prediction
estimation.
Sample-specific
interpretability
enabled
through
weights.
Aging
interventions
have
progressed
in
recent
years
due
to
the
growing
curiosity
about
how
lifestyle
impacts
longevity.
This
study
assessed
effects
of
SRW
Laboratories'
Cel
System
nutraceutical
range
on
epigenetic
methylation
patterns,
inflammation,
physical
performance,
body
composition,
and
biomarkers
aging.
A
1-year
was
conducted
with
51
individuals,
collecting
data
at
baseline,
3
months,
6
12
months.
Participants
were
encouraged
walk
10
minutes
practice
5
mindfulness
daily.
Significant
improvements
muscle
strength,
function,
composition
metrics
observed.
Epigenetic
clock
analysis
showed
a
decrease
biological
age
significant
reductions
stem
cell
division
rates.
Immune
subset
indicated
changes,
increases
eosinophils
CD8T
cells
decreases
B
memory,
CD4T
T-regulatory
cells.
Predicted
biomarker
proxies
(EBPs)
changes
retinol/TTHY,
regulator
growth,
proliferation,
differentiation,
deoxycholic
acid
glucuronide
levels,
metabolite
generated
liver.
Gene
ontology
revealed
CpG
genes
involved
critical
processes
related
aging,
such
as
oxidative
stress-induced
premature
senescence,
pyrimidine
deoxyribonucleotide
metabolic
process,
TRAIL
binding,
hyaluronan
biosynthetic
neurotransmitter
loading
into
synaptic
vesicles,
pore
complex
assembly,
collagen
protein
phosphatase
2A
binding
activity,
activation
transcription
factor
binding.
Our
findings
suggest
that
supplement
may
effectively
reduce
improve
health
metrics,
warranting
further
investigation
its
mechanistic
pathways
long-term
efficacy.
Abstract
Usage
of
the
phrase
“biological
age”
has
picked
up
considerably
since
advent
aging
clocks
and
it
become
commonplace
to
describe
an
clock's
output
as
biological
age.
In
contrast
this
labeling,
age
is
also
often
depicted
a
more
abstract
concept
that
helps
explain
how
individuals
are
internally,
externally,
functionally.
Given
bulk
molecular
tissue‐specific
itself
remarkably
complex,
multifarious
process,
unsurprising
most
surveyed
scientists
agree
cannot
be
quantified
via
single
metric.
We
share
sentiment
argue
that,
just
like
would
not
reasonable
assume
individual
with
ideal
grip
strength,
VO
2
max,
or
any
other
biomarker
biologically
young,
we
should
careful
conflate
clock
whole‐body
aging.
To
address
this,
recommend
researchers
based
on
type
input
data
used
name
itself.
Epigenetic
produce
epigenetic
age,
transcriptomic
so
forth.
If
unique
name,
such
our
recently
developed
CheekAge,
can
double
output.
As
compromise
solution,
biomarkers
described
indicators
feel
these
recommendations
will
help
public
differentiate
between
much
elusive
