Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 2, 2023
Abstract
Aging
clocks
have
provided
one
of
the
most
significant
recent
breakthroughs
in
biology
aging.
Such
allow
determination
chronological
and
increasingly
also
biological
age,
which
is
a
prerequisite
for
assessing
effectiveness
interventions
aging
process
preventive
treatments
age-related
diseases.
The
advanced
are
based
on
age-dependent
changes
DNA
methylation
pattern.
reproducibility
such
over
life
course
has
reinvigorated
debate
whether
programmed
underlies
A
process,
however,
incompatible
with
evolutionary
theory
occurs
as
consequence
vanishing
force
selective
pressure
post-reproduction
no
fitness
benefit
by
immortality
soma.
In
fact,
stochastic
events
been
observed
to
occur
during
process.
Here,
we
test
could
be
built
entirely
variation.
We
find
that
accumulating
variation
sufficient
accurately
predict
age.
Moreover,
current
compatible
random
alterations
or
transcriptomic
patterns.
Our
analysis
unifies
clock
measure
predicts
any
set
data
ground
state
at
age
zero
used
building
accurate
clocks.
Nature Aging,
Год журнала:
2024,
Номер
4(6), С. 871 - 885
Опубликована: Май 9, 2024
Abstract
Aging
clocks
have
provided
one
of
the
most
important
recent
breakthroughs
in
biology
aging,
and
may
provide
indicators
for
effectiveness
interventions
aging
process
preventive
treatments
age-related
diseases.
The
reproducibility
accurate
has
reinvigorated
debate
on
whether
a
programmed
underlies
aging.
Here
we
show
that
accumulating
stochastic
variation
purely
simulated
data
is
sufficient
to
build
clocks,
first-generation
second-generation
are
compatible
with
accumulation
DNA
methylation
or
transcriptomic
data.
We
find
predict
chronological
biological
age,
indicated
by
significant
prediction
differences
smoking,
calorie
restriction,
heterochronic
parabiosis
partial
reprogramming.
Although
our
simulations
not
explicitly
rule
out
process,
results
suggest
stochastically
changes
any
set
ground
state
at
age
zero
generating
clocks.
Aging
is
a
complex
and
multifaceted
process
involving
many
epigenetic
alterations.
One
key
area
of
interest
in
aging
research
the
role
histone
modifications,
which
can
dynamically
regulate
gene
expression.
Here,
we
conducted
pan-tissue
analysis
dynamics
seven
modifications
during
human
aging.
Our
histone-specific
age
prediction
models
showed
surprisingly
accurate
performance,
proving
resilient
to
experimental
artificial
noise.
Simulation
experiments
for
comparison
with
DNA
methylation
predictors
revealed
competitive
performance.
Moreover,
set
enrichment
uncovered
several
critical
developmental
pathways
prediction.
Different
from
predictors,
genes
known
be
involved
biology
are
among
most
important
ones
models.
Last,
developed
pan-histone
predictor,
suggesting
that
age-related
information
degenerated
across
epigenome.
This
highlights
power
marks
as
input
creating
robust
opens
avenues
understanding
changes
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Ноя. 1, 2022
Abstract
Age
is
the
leading
risk
factor
for
prevalent
diseases
and
death.
However,
relation
between
age-related
physiological
changes
lifespan
poorly
understood.
We
combined
analytical
machine
learning
tools
to
describe
aging
process
in
large
sets
of
longitudinal
measurements.
Assuming
that
results
from
a
dynamic
instability
organism
state,
we
designed
deep
artificial
neural
network,
including
auto-encoder
auto-regression
(AR)
components.
The
AR
model
tied
dynamics
state
with
stochastic
evolution
single
variable,
“dynamic
frailty
indicator”
(dFI).
In
subset
blood
tests
Mouse
Phenome
Database,
dFI
increased
exponentially
predicted
remaining
lifespan.
observation
limiting
was
consistent
late-life
mortality
deceleration.
changed
along
hallmarks
aging,
index,
molecular
markers
inflammation,
senescent
cell
accumulation,
responded
life-shortening
(high-fat
diet)
life-extending
(rapamycin)
treatments.
Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 30, 2023
Abstract
Aging
clocks
have
provided
one
of
the
most
significant
recent
breakthroughs
in
biology
aging.
Such
allow
determination
chronological
and
increasingly
also
biological
age,
which
is
prerequisite
for
assessing
effectiveness
interventions
aging
process
preventive
treatments
age-related
diseases.
The
advanced
are
based
on
age-dependent
changes
DNA
methylation
pattern.
reproducibility
such
over
life
course
has
reinvigorated
debate
whether
a
programmed
underlies
A
process,
however,
incompatibly
with
evolutionary
theory
occurs
as
consequence
vanishing
force
selective
pressure
post-reproduction
no
fitness
benefit
by
immortality
soma.
In
fact,
stochastic
events
been
observed
to
occur
during
process.
Here,
we
test
could
be
built
entirely
variation.
We
find
that
accumulating
variation
sufficient
accurately
predict
age.
Moreover,
current
compatible
random
alterations
or
transcriptomic
patterns.
Our
analysis
unifies
clock
measure
predicts
any
set
data
ground
state
at
age
zero
used
building
accurate
clocks.
Aging
is
a
process
that
affects
almost
all
multicellular
organisms
and
since
our
population
ages
with
increasing
prevalence
of
age-related
diseases,
it
important
to
study
basic
processes
involved
in
aging.
Many
studies
have
been
published
so
far
using
different
often
single
age
markers
estimate
the
biological
or
cell
culture
systems.
However,
comparability
hampered
by
lack
uniform
panel
markers.
Consequently,
we
here
suggest
an
easy-to-use
biomarker-based
classical
systems
can
be
used
standard
laboratories.
This
shown
sensitive
variety
aging
conditions.
We
primary
human
skin
fibroblasts
donor
additionally
induced
either
replicative
senescence
artificial
progerin
overexpression.
Using
this
panel,
highest
was
found
for
Our
data
display
varies
depending
on
line
model
even
from
individual
showing
need
comprehensive
analyses.
Biology,
Год журнала:
2025,
Номер
14(4), С. 349 - 349
Опубликована: Март 27, 2025
The
Constrained
Disorder
Principle
(CDP)
offers
a
new
framework
for
understanding
how
biological
systems
use
and
manage
noise
to
maintain
optimal
functionality.
This
review
explores
the
relationship
between
at
various
scales,
including
genetic,
cellular,
organ
levels,
its
implications
system
malfunctions.
According
CDP,
all
require
an
range
of
function
appropriately,
disease
states
can
arise
when
these
levels
are
disrupted.
presents
evidence
supporting
this
principle
across
different
contexts,
such
as
genetic
variability,
cellular
behavior,
brain
functions,
human
aging,
evolution,
drug
administration.
For
accurate
clinical
assessments,
it
is
essential
distinguish
technical
variability
intrinsic
variability.
When
adequately
constrained,
serves
fundamental
mechanism
adaptation
functioning
rather
than
simply
source
disruption.
These
findings
have
important
developing
more
effective
therapeutic
strategies
systems’
dynamics.
CDP-based
second-generation
artificial
intelligence
help
regulate
address
improved
outcomes
in
conditions
by
incorporating
controlled
randomness.
Understanding
patterns
has
significant
diagnosis,
treatment
monitoring,
development
medical
conditions.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Сен. 28, 2022
Abstract
Age-related
changes
in
DNA
methylation
(DNAm)
form
the
basis
for
development
of
most
robust
predictors
age,
epigenetic
clocks,
but
a
clear
mechanistic
exactly
what
part
aging
process
they
quantify
is
lacking.
Here,
to
clarify
nature
aging,
we
juxtapose
dynamics
tissue
and
single-cell
DNAm
(scDNAm)
with
scDNAm
during
early
development,
corroborate
our
analyses
RNAseq
analysis
within
same
multi-omics
dataset.
We
show
that
involves
co-regulated
changes,
it
dominated
by
stochastic
component,
this
agrees
transcriptional
coordination
patterns.
further
support
finding
direct
modeling
trajectories
akin
radiocarbon
decay.
Finally,
describe
algorithm
identification
CpG
clusters
showing
consistent
transcriptomic
patterns,
providing
new
opportunities
targeting
evaluating
longevity
interventions.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 28, 2024
Aging
across
most
species,
including
mice
and
humans,
is
characterized
by
an
exponential
acceleration
of
mortality
rates.
In
search
for
the
molecular
basis
this
phenomenon,
we
analyzed
DNA
methylation
(DNAm)
changes
in
aging
mice.
Utilizing
principal
component
analysis
(PCA)
on
DNAm
profiles,
identified
a
primary
signature
with
age
dependency,
closely
reflecting
Gompertz
law’s
description
acceleration.
This
manifestation
dynamic
instability
organism’s
state
that
drives
process
It
aligns
regression-based
clocks
responds
to
interventions
such
as
caloric
restriction
parabiosis.
Additionally,
linear
signature,
indicative
global
demethylation
level.
Through
single-cell
(scDNAm)
data
from
animals,
demonstrate
captures
expansion
space
volume
spanned
individual
cells
within
organism,
thus
quantifying
linearly
increasing
configuration
entropy,
likely
irreversible
process.
Consistent
interpretation,
found
neither
(CR)
nor
parabiosis
significantly
impacts
entropic
feature,
reinforcing
its
link
damage.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(12), С. 6793 - 6793
Опубликована: Июнь 20, 2024
Aging
is
a
complex
and
time-dependent
decline
in
physiological
function
that
affects
most
organisms,
leading
to
increased
risk
of
age-related
diseases.
Investigating
the
molecular
underpinnings
aging
crucial
identify
geroprotectors,
precisely
quantify
biological
age,
propose
healthy
longevity
approaches.
This
review
explores
pathways
are
currently
being
investigated
as
intervention
targets
biomarkers
spanning
molecular,
cellular,
systemic
dimensions.
Interventions
target
these
hallmarks
may
ameliorate
process,
with
some
progressing
clinical
trials.
Biomarkers
used
estimate
aging-associated
disease.
Utilizing
biomarkers,
clocks
can
be
constructed
predict
state
abnormal
aging,
diseases,
mortality.
Biological
age
estimation
therefore
provide
basis
for
fine-grained
stratification
by
predicting
all-cause
mortality
well
ahead
onset
specific
thus
offering
window
intervention.
Yet,
despite
technological
advancements,
challenges
persist
due
individual
variability
dynamic
nature
biomarkers.
Addressing
this
requires
longitudinal
studies
robust
biomarker
identification.
Overall,
utilizing
discover
new
drug
develop
opens
frontiers
medicine.
Prospects
involve
multi-omics
integration,
machine
learning,
personalized
approaches
targeted
interventions,
promising
healthier
population.
