International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1772 - 1772
Опубликована: Фев. 19, 2025
Ribosome
biogenesis
is
one
of
the
most
fundamental
and
energetically
demanding
cellular
processes.
In
humans,
ribosomal
DNA
(rDNA)
repeats
span
a
large
region
comprise
200
to
600
copies
~43
kb
unit
spread
over
five
different
chromosomes.
Control
ribosome
closely
tied
regulation
chromatin
environment
this
genomic
region.
The
proportion
rDNA
loci
which
are
active
or
silent
altered
depending
on
proliferative
metabolic
state
cell.
Repeat
silencing
driven
by
epigenetic
changes
culminating
in
repressive
heterochromatin
environment.
One
group
proteins
facilitating
these
response
growth
demands
ATP-dependent
remodeling
protein
complexes
that
use
ATP
hydrolysis
reposition
nucleosomes.
Indeed,
some
remodelers
known
have
indispensable
roles
regulating
rDNA.
review,
we
highlight
their
describe
mechanistic
at
We
also
introduce
developmental
disorders
arising
from
dysfunction
discuss
how
consequent
dysregulation
may
be
reflected
phenotypes
observed.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Ноя. 21, 2019
Abstract
Metabolic
dysfunction
is
a
primary
feature
of
Werner
syndrome
(WS),
human
premature
aging
disease
caused
by
mutations
in
the
gene
encoding
(WRN)
DNA
helicase.
WS
patients
exhibit
severe
metabolic
phenotypes,
but
underlying
mechanisms
are
not
understood,
and
whether
deficit
can
be
targeted
for
therapeutic
intervention
has
been
determined.
Here
we
report
impaired
mitophagy
depletion
NAD
+
,
fundamental
ubiquitous
molecule,
patient
samples
invertebrate
models.
WRN
regulates
transcription
key
biosynthetic
enzyme
nicotinamide
nucleotide
adenylyltransferase
1
(NMNAT1).
repletion
restores
profiles
improves
mitochondrial
quality
through
DCT-1
ULK-1-dependent
mitophagy.
At
organismal
level,
remarkably
extends
lifespan
delays
accelerated
aging,
including
stem
cell
dysfunction,
Caenorhabditis
elegans
Drosophila
melanogaster
models
WS.
Our
findings
suggest
that
mediated
function
mitophagy,
bolstering
cellular
levels
counteracts
phenotypes.
Nucleic Acids Research,
Год журнала:
2020,
Номер
48(19), С. 11083 - 11096
Опубликована: Сен. 23, 2020
Abstract
N6-Methyladenosine
(m6A)
messenger
RNA
methylation
is
a
well-known
epitranscriptional
regulatory
mechanism
affecting
central
biological
processes,
but
its
function
in
human
cellular
senescence
remains
uninvestigated.
Here,
we
found
that
levels
of
both
m6A
and
the
methyltransferase
METTL3
were
reduced
prematurely
senescent
mesenchymal
stem
cell
(hMSC)
models
progeroid
syndromes.
Transcriptional
profiling
modifications
further
identified
MIS12,
for
which
hMSCs
METTL3-deficient
hMSCs.
Knockout
accelerated
hMSC
whereas
overexpression
rescued
phenotypes.
Mechanistically,
loss
turnover
decreased
expression
MIS12
mRNA
while
knockout
senescence.
Furthermore,
reader
IGF2BP2
was
as
key
player
recognizing
stabilizing
m6A-modified
mRNA.
Taken
together,
discovered
alleviates
through
modification-dependent
stabilization
transcript,
representing
novel
premature
Experimental & Molecular Medicine,
Год журнала:
2020,
Номер
52(9), С. 1466 - 1474
Опубликована: Сен. 1, 2020
Abstract
Aging
is
an
inevitable
process
of
life.
Defined
by
progressive
physiological
and
functional
loss
tissues
organs,
aging
increases
the
risk
mortality
for
organism.
The
affected
various
factors,
including
genetic
epigenetic
ones.
Here,
we
review
chromatin-specific
changes
that
occur
during
normal
(chronological)
in
premature
diseases.
Taking
advantage
reversible
nature
modifications,
will
also
discuss
possible
lifespan
expansion
strategies
through
modulation,
which
was
considered
irreversible
until
recently.
Protein & Cell,
Год журнала:
2018,
Номер
10(6), С. 417 - 435
Опубликована: Авг. 1, 2018
Aging
increases
the
risk
of
various
diseases.
The
main
goal
aging
research
is
to
find
therapies
that
attenuate
and
alleviate
aging-related
In
this
study,
we
screened
a
natural
product
library
for
geroprotective
compounds
using
Werner
syndrome
(WS)
human
mesenchymal
stem
cells
(hMSCs),
premature
model
recently
established.
Ten
candidate
were
identified
quercetin
was
investigated
in
detail
due
its
leading
effects.
Mechanistic
studies
revealed
alleviated
senescence
via
enhancement
cell
proliferation
restoration
heterochromatin
architecture
WS
hMSCs.
RNA-sequencing
analysis
transcriptional
commonalities
differences
effects
by
Vitamin
C.
Besides
hMSCs,
also
attenuated
cellular
Hutchinson-Gilford
progeria
(HGPS)
physiological-aging
Taken
together,
our
study
identifies
as
agent
against
accelerated
providing
potential
therapeutic
intervention
treating
age-associated
disorders.
Protein & Cell,
Год журнала:
2018,
Номер
9(4), С. 333 - 350
Опубликована: Фев. 23, 2018
Hutchinson-Gilford
progeria
syndrome
(HGPS)
and
Werner
(WS)
are
two
of
the
best
characterized
human
progeroid
syndromes.
HGPS
is
caused
by
a
point
mutation
in
lamin
A
(LMNA)
gene,
resulting
production
truncated
protein
product—progerin.
WS
mutations
WRN
encoding
loss-of-function
RecQ
DNA
helicase.
Here,
gene
editing
we
created
isogenic
embryonic
stem
cells
(ESCs)
with
heterozygous
(G608G/+)
or
homozygous
(G608G/G608G)
LMNA
biallelic
knockout,
for
modeling
pathogenesis,
respectively.
While
ESCs
endothelial
(ECs)
did
not
present
any
features
premature
senescence,
HGPS-
WS-mesenchymal
(MSCs)
showed
aging-associated
phenotypes
different
kinetics.
WS-MSCs
had
early-onset
mild
aging
while
HGPS-MSCs
exhibited
late-onset
acute
characterisitcs.
Taken
together,
our
study
compares
contrasts
distinct
pathologies
underpinning
disorders,
provides
reliable
stem-cell
based
models
to
identify
new
therapeutic
strategies
pathological
physiological
aging.
International Journal of Medical Sciences,
Год журнала:
2020,
Номер
17(11), С. 1625 - 1638
Опубликована: Янв. 1, 2020
Oxidative
stress
and
inflammation
are
two
interlinked
events
that
exist
simultaneously
in
metabolic
syndrome
(MetS)
its
related
complications.These
pathophysiological
processes
can
be
easily
triggered
by
each
other.This
review
summarizes
the
current
evidence
from
animal
human
studies
on
effects
of
vitamin
C
managing
MetS.In
vivo
showed
promising
C,
but
most
interventions
used
were
combination
with
other
compounds.The
direct
remain
to
elucidated.In
humans,
state
revealed
lower
intake
circulating
concentration
found
MetS
subjects.A
negative
relationship
was
observed
between
/
risk
MetS.Oral
supplementation
also
improved
conditions.It
has
been
postulated
positive
outcomes
may
part
mediated
through
anti-oxidative
anti-inflammatory
properties.These
observations
suggest
importance
patients
have
an
adequate
food,
beverages
or
supplements
order
maintain
systemic
circulation
potentially
reverse
MetS.
Frontiers in Cell and Developmental Biology,
Год журнала:
2021,
Номер
9
Опубликована: Фев. 25, 2021
RecQ
DNA
helicases
are
a
conserved
protein
family
found
in
bacteria,
fungus,
plants,
and
animals.
These
play
important
roles
multiple
cellular
functions,
including
replication,
transcription,
repair,
telomere
maintenance.
Humans
have
five
helicases:
RECQL1,
Bloom
syndrome
(BLM),
Werner
helicase
(WRN),
RECQL4,
RECQL5.
Defects
BLM
WRN
cause
autosomal
disorders:
(BS)
(WS),
respectively.
Mutations
RECQL4
associated
with
three
genetic
disorders,
Rothmund–Thomson
(RTS),
Baller–Gerold
(BGS),
RAPADILINO
syndrome.
Although
no
disorders
been
reported
due
to
loss
of
RECQL1
or
RECQL5,
dysfunction
either
gene
is
tumorigenesis.
Multiple
genetically
independent
pathways
evolved
that
mediate
the
repair
double-strand
break
(DSB),
pivotal
each
them.
The
importance
DSB
supported
by
observations
defective
can
chromosomal
aberrations,
genomic
instability,
senescence,
cell
death,
which
ultimately
lead
premature
aging,
neurodegeneration,
In
this
review,
we
will
introduce
human
family,
describe
detail
their
provide
relevance
between
diseases.
Mechanisms of Ageing and Development,
Год журнала:
2020,
Номер
186, С. 111208 - 111208
Опубликована: Янв. 15, 2020
Nicotinamide
adenine
dinucleotide
(NAD+)
plays
a
fundamental
role
in
life
and
health
through
the
regulation
of
energy
biogenesis,
redox
homeostasis,
cell
metabolism,
arbitration
survival
via
linkages
to
apoptosis
autophagic
pathways.
The
importance
NAD+
ageing
healthy
longevity
has
been
revealed
from
laboratory
animal
studies
early-stage
clinical
testing.
While
basic
researchers
clinicians
have
investigated
molecular
mechanisms
translation
potential
NAD+,
there
are
still
major
gaps
applying
science
design
most
effective
trials.
This
mini-review
was
based
on
programme
discussions
3rd
NO-Age
Symposium
held
at
Akershus
University
Hospital,
Norway
28th
October
2019.
symposium
brought
together
leading
who
or
going
perform
augmentation-related
studies.
meeting
covered
talks
about
synthetic
pathways,
subcellular
homeostasis
benefits
augmentation
maternal
milk
offspring,
current
trials
precursor
nicotinamide
riboside
(NR)
Ataxia-Telangiectasia
(A-T),
Parkinson's
disease
(PD),
post-sepsis
fatigue,
as
well
other
NR-based
Importantly,
consensus
is
emerging
with
respect
order
measure
meaningful
parameters
ensure
safety.
Physiological Reviews,
Год журнала:
2022,
Номер
102(3), С. 1449 - 1494
Опубликована: Март 28, 2022
Aging
is
the
single
largest
risk
factor
for
many
debilitating
conditions,
including
heart
diseases,
stroke,
cancer,
diabetes,
and
neurodegenerative
disorders.
Although
far
from
understood
in
its
full
complexity,
it
scientifically
well
established
that
aging
influenced
by
genetic
environmental
factors
can
be
modulated
various
interventions.
One
of
aging's
early
hallmarks
aberrations
transcriptional
networks,
controlling
example
metabolic
homeostasis
or
response
to
stress.
Evidence
different
model
organisms
abounds
a
number
evolutionarily
conserved
transcription
factors,
which
control
such
affect
life
span
health
across
species.
These
thus
potentially
represent
regulators
longevity
are
emerging
as
important
targets
challenging
quest
develop
treatments
mitigate
age-related
possibly
even
slow
itself.
This
review
provides
an
overview
impact
diseases
at
least
one
multicellular
organism
(nematodes,
flies,
mice)
and/or
tentatively
linked
human
aging.
Discussed
general
evidence
regulation
disease,
followed
more
detailed
look
selected
families,
common
pathways
involved,
targeting
strategy
geroprotective