Abstract
A
key
goal
of
aging
research
was
to
understand
mechanisms
underlying
healthy
and
develop
methods
promote
the
human
healthspan.
One
approach
is
identify
gene
regulations
unique
compared
with
in
general
population
(i.e.,
“common”
aging).
Here,
we
leveraged
Genotype‐Tissue
Expression
(GTEx)
project
data
investigate
“healthy”
expression
at
a
tissue
level
humans
their
interconnection
diseases.
Using
GTEx
donors'
disease
annotations,
defined
cohort
for
each
tissue.
We
then
age‐associated
genes
derived
from
this
which
included
all
donors;
also
expressions
various
disease‐associated
elucidate
relationships
among
“healthy,”
disease.
Our
analyses
showed
that
1.
shared
large
number
regulations;
2.
Despite
substantial
commonality,
distinct
function
enrichment,
had
higher
enrichment
genes;
3.
Disease‐associated
were
overall
different
regulations.
However,
regulated
by
both,
regulation
directions
largely
consistent,
implying
some
processes
could
increase
susceptibility
development;
4.
Possible
protective
associated
In
summary,
our
work
highlights
several
features
program.
This
new
knowledge
potentially
be
used
interventions
Cell Reports,
Год журнала:
2023,
Номер
42(1), С. 111982 - 111982
Опубликована: Янв. 1, 2023
Cellular
circadian
clocks
direct
a
daily
transcriptional
program
that
supports
homeostasis
and
resilience.
Emerging
evidence
has
demonstrated
age-associated
changes
in
functions.
To
define
age-dependent
at
the
systems
level,
we
profile
transcriptome
hypothalamus,
lung,
heart,
kidney,
skeletal
muscle,
adrenal
gland
three
age
groups.
We
find
tissue-specific
clock
output
changes.
Aging
reduces
number
of
rhythmically
expressed
genes
(REGs),
indicative
weakened
control.
REGs
are
enriched
for
hallmarks
aging,
adding
another
dimension
to
our
understanding
aging.
Analyzing
differential
gene
expression
within
tissue
four
different
times
day
identifies
distinct
clusters
differentially
(DEGs).
Increased
variability
across
is
common
feature
aged
tissues.
This
analysis
extends
landscape
aging
highlights
impact
on
function
temporal
expression.
Acta Neuropathologica,
Год журнала:
2024,
Номер
147(1)
Опубликована: Май 9, 2024
Abstract
Aging
affects
all
cell
types
in
the
CNS
and
plays
an
important
role
diseases.
However,
underlying
molecular
mechanisms
driving
these
age-associated
changes
their
contribution
to
diseases
are
only
poorly
understood.
The
white
matter
aging
brain
as
well
diseases,
such
Multiple
sclerosis
is
characterized
by
subtle
abnormalities
myelin
sheaths
paranodes,
suggesting
that
oligodendrocytes,
myelin-maintaining
cells
of
CNS,
lose
capacity
preserve
a
proper
structure
potentially
function
age
certain
Here,
we
made
use
directly
converted
oligodendrocytes
(dchiOL)
from
young,
adult
old
human
donors
study
changes.
dchiOL
three
groups
differentiated
comparable
manner
into
O4
+
immature
but
proportion
MBP
mature
decreased
with
increasing
donor
age.
This
was
associated
increased
ROS
production
upregulation
cellular
senescence
markers
CDKN1A,
CDKN2A
dchiOL.
Comparison
transcriptomic
profiles
revealed
1324
differentially
regulated
genes
limited
overlap
donors’
fibroblasts
or
published
data
sets
neurons
primary
rodent
oligodendroglial
lineage
cells.
Methylome
analyses
tissue
samples
demonstrate
chronological
epigenetic
correlate
resulted
identification
age-specific
signature.
Furthermore,
observed
accelerated
myelinated,
normal
appearing
multiple
(MS)
patients
compared
healthy
individuals.
Impaired
differentiation
could
be
induced
young
vitro
using
supernatants
pro-inflammatory
microglia.
In
summary,
our
suggest
physiological
inflammation-induced
contribute
pathology
inflammatory
demyelinating
MS.
Trends in Genetics,
Год журнала:
2024,
Номер
40(4), С. 299 - 312
Опубликована: Март 21, 2024
Recent
studies
of
aging
organisms
have
identified
a
systematic
phenomenon,
characterized
by
negative
correlation
between
gene
length
and
their
expression
in
various
cell
types,
species,
diseases.
We
term
this
phenomenon
gene-length-dependent
transcription
decline
(GLTD)
suggest
that
it
may
represent
bottleneck
the
machinery
thereby
significantly
contribute
to
as
an
etiological
factor.
review
potential
links
GLTD
key
processes
such
DNA
damage
explore
identifying
disease
modification
targets.
Notably,
Alzheimer's
disease,
spotlights
extremely
long
synaptic
genes
at
chromosomal
fragile
sites
(CFSs)
vulnerability
postmitotic
damage.
is
integral
element
biological
aging.
Physical Review Research,
Год журнала:
2025,
Номер
7(1)
Опубликована: Март 28, 2025
Aging
is
driven
by
damage
accumulation
leading
to
a
decline
in
function
over
time.
In
single-cell
systems,
addition
this
within
individuals,
asymmetric
partitioning
at
cell
division
can
play
crucial
role
shaping
demographic
aging
patterns.
Despite
experimental
studies
that
provide
quantitative
data
the
molecular
and
levels,
integration
of
complementary
theory
explaining
how
cellular
production
propagate
influence
patterns
still
lacking.
Here,
we
present
generic
flexible
model
using
stochastic
differential
equation
approach
incorporates
during
divisions.
We
formulate
an
analytical
approximation
linking
parameters
along
mother
lineages.
Interestingly,
lifespan
cells
follows
inverse
Gaussian
distribution,
whose
underlying
properties
derive
from
parameters.
demonstrate
stochasticity
(noise)
production,
asymmetry
partitioning,
frequency
shape
distribution.
Confronting
with
various
empirical
machine
reveals
nonexponential
scaling
mortality
rates,
cannot
be
captured
classical
Gompertz-Makeham
models.
Our
findings
deeper
understanding
fundamental
processes
contribute
dynamics
generate
model's
nature
offers
valuable
framework
for
investigating
diverse
biological
systems.
Published
American
Physical
Society
2025
Aging Medicine,
Год журнала:
2018,
Номер
1(2), С. 158 - 175
Опубликована: Июль 30, 2018
Abstract
Aging
is
progressive
physiological
degeneration
and
consequently
declined
function,
which
linked
to
senescence
on
both
cellular
organ
levels.
Accumulating
studies
indicate
that
long
noncoding
RNA
s
(lnc
s)
play
important
roles
in
at
all
levels—transcriptional,
post‐transcriptional,
translational,
post‐translational.
Understanding
the
molecular
mechanism
of
lnc
underlying
could
facilitate
interpretation
intervention
aging
age‐related
diseases.
In
this
review,
we
describe
categories
known
novel
have
been
involved
progression
senescence.
We
also
identify
implicated
diseases
arising
from
age‐driven
or
dysfunction
some
representative
organs
systems
(brains,
liver,
muscle,
cardiovascular
system,
bone
pancreatic
islets,
immune
system).
Improved
comprehension
process
levels,
cell
organismal,
may
provide
new
insights
into
amelioration
pathologies
prolonged
healthspan.
