The
mechanisms
contributing
to
age-related
deterioration
of
the
female
reproductive
system
are
complex,
however
aberrant
protein
homeostasis
is
a
major
contributor.
We
elucidated
exceptionally
stable
proteins,
structures,
and
macromolecules
that
persist
in
mammalian
ovaries
gametes
across
lifespan.
Ovaries
exhibit
localized
structural
cell-type
specific
enrichment
both
follicular
extrafollicular
environments.
Moreover,
oocytes
harbor
panel
long-lived
including
cytoskeletal,
mitochondrial,
oocyte-derived
proteins.
exceptional
persistence
these
molecules
suggest
critical
role
lifelong
maintenance
age-dependent
tissues.
Human Reproduction Update,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 20, 2025
Ovarian
aging
occurs
earlier
than
the
of
many
other
organs
and
has
a
lasting
impact
on
women's
overall
health
well-being.
However,
effective
interventions
to
slow
ovarian
remain
limited,
primarily
due
an
incomplete
understanding
underlying
molecular
mechanisms
drug
targets.
Recent
advances
in
omics
data
resources,
combined
with
innovative
computational
tools,
are
offering
deeper
insight
into
complexities
aging,
paving
way
for
new
opportunities
discovery
development.
This
review
aims
synthesize
expanding
multi-omics
data,
spanning
genome,
transcriptome,
proteome,
metabolome,
microbiome,
related
from
both
tissue-level
single-cell
perspectives.
We
will
specially
explore
how
analysis
these
emerging
datasets
can
be
leveraged
identify
novel
targets
guide
therapeutic
strategies
slowing
reversing
aging.
conducted
comprehensive
literature
search
PubMed
database
using
range
relevant
keywords:
age
at
natural
menopause,
premature
insufficiency
(POI),
diminished
reserve
(DOR),
genomics,
transcriptomics,
epigenomics,
DNA
methylation,
RNA
modification,
histone
proteomics,
metabolomics,
lipidomics,
single-cell,
genome-wide
association
studies
(GWAS),
whole-exome
sequencing,
phenome-wide
(PheWAS),
Mendelian
randomization
(MR),
epigenetic
target,
machine
learning,
artificial
intelligence
(AI),
deep
multi-omics.
The
was
restricted
English-language
articles
published
up
September
2024.
Multi-omics
have
uncovered
key
driving
including
damage
repair
deficiencies,
inflammatory
immune
responses,
mitochondrial
dysfunction,
cell
death.
By
integrating
researchers
critical
regulatory
factors
across
various
biological
levels,
leading
potential
Notable
examples
include
genetic
such
as
BRCA2
TERT,
like
Tet
FTO,
metabolic
sirtuins
CD38+,
protein
BIN2
PDGF-BB,
transcription
FOXP1.
advent
cutting-edge
technologies,
especially
technologies
spatial
provided
valuable
insights
guiding
treatment
decisions
become
powerful
tool
aimed
mitigating
or
As
technology
advances,
integration
AI
models
holds
more
accurately
predict
candidate
convergence
offers
promising
avenues
personalized
medicine
precision
therapies,
tailored
Not
applicable.
Abstract
Nicotinamide
adenine
dinucleotide
(NAD+),
a
crucial
coenzyme
in
cellular
redox
reactions,
is
closely
associated
with
age-related
functional
degeneration
and
metabolic
diseases.
NAD
exerts
direct
indirect
influences
on
many
functions,
including
pathways,
DNA
repair,
chromatin
remodeling,
senescence,
immune
cell
functionality.
These
processes
functions
are
essential
for
maintaining
tissue
homeostasis,
as
well
healthy
aging.
Causality
has
been
elucidated
between
decline
levels
multiple
diseases,
which
confirmed
by
various
strategies
aimed
at
increasing
the
preclinical
setting.
Ovarian
aging
recognized
natural
process
characterized
follicle
number
function,
resulting
decreased
estrogen
production
menopause.
In
this
regard,
it
necessary
to
address
factors
involved
complicated
procedure,
could
improve
fertility
women
of
advanced
maternal
age.
Concerning
decrease
NAD+
ovarian
progresses,
promising
exciting
results
presented
using
precursors
promote
biosynthesis,
substantially
oocyte
quality
alleviate
Hence,
acquire
further
insights
into
metabolism
biology,
review
aims
probe
affecting
aging,
characteristics
precursors,
current
research
status
supplementation
Specifically,
gaining
comprehensive
understanding
these
aspects,
we
optimistic
about
prominent
progress
that
will
be
made
both
therapy
related
Abstract
This
review
explores
the
relationship
between
ovarian
aging
and
senescent
cell
accumulation,
as
well
efficacy
of
senolytics
to
improve
reproductive
longevity.
Reproductive
longevity
is
determined
by
age-associated
decline
in
reserve,
resulting
reduced
fertility
eventually
menopause.
Cellular
senescence
a
state
permanent
cycle
arrest
resistance
apoptosis.
Senescent
cells
accumulate
several
tissues
with
advancing
age,
thereby
promoting
chronic
inflammation
age-related
diseases.
Ovaries
also
appear
which
might
contribute
system
whole
organism
through
SASP
production.
Importantly,
senolytic
drugs
can
eliminate
may
present
potential
intervention
mitigate
aging.
Herein,
we
current
literature
related
for
extending
window
mice.
The
mechanisms
contributing
to
age-related
deterioration
of
the
female
reproductive
system
are
complex,
however
aberrant
protein
homeostasis
is
a
major
contributor.
We
elucidated
exceptionally
stable
proteins,
structures,
and
macromolecules
that
persist
in
mammalian
ovaries
gametes
across
lifespan.
Ovaries
exhibit
localized
structural
cell-type-specific
enrichment
both
follicular
extrafollicular
environments.
Moreover,
oocytes
harbor
panel
long-lived
including
cytoskeletal,
mitochondrial,
oocyte-derived
proteins.
exceptional
persistence
these
molecules
suggest
critical
role
lifelong
maintenance
age-dependent
tissues.
Antioxidants,
Год журнала:
2024,
Номер
13(7), С. 859 - 859
Опубликована: Июль 18, 2024
Astragalin
(AG),
a
typical
flavonoid
found
in
Thesium
chinense
Turcz
(T.
chinense),
is
abundant
various
edible
plants
and
possesses
high
nutritional
value,
as
well
antioxidant
antibacterial
effects.
In
this
study,
we
initially
predicted
the
mechanism
of
action
AG
with
two
anti-aging
antioxidant-related
protein
targets
(CD38
IGFR)
by
molecular
docking
dynamics
simulation
techniques.
Subsequently,
examined
effects
Caenorhabditis
elegans
(C.
elegans),
zebrafish,
verified
related
mechanisms.
C.
elegans,
synergistically
extended
lifespan
up-regulating
expression
daf-16
through
inhibiting
daf-2/IGFR
also
activating
AMPK
MAPK
pathways
to
up-regulate
sir-2.1,
sir-2.4,
skn-1.
oxidatively
damaged
zebrafish
embryos,
demonstrated
synergistic
effect
augmenting
resistance
embryos
oxidative
stress
levels
SIRT1
SIRT6
within
system
via
suppression
CD38
enzymatic
activity
then
IGFR
SIRT6.
These
findings
highlight
properties
indicate
its
potential
application
supplementary
ingredient
aquaculture
for
enhancing
fish
health
growth.
The FASEB Journal,
Год журнала:
2024,
Номер
38(14)
Опубликована: Июль 22, 2024
Abstract
Natural
Nicotinamide
Adenine
Dinucleotide
(NAD
+
)
precursors
have
attracted
much
attention
due
to
their
positive
effects
in
promoting
ovarian
health.
However,
target
tissue,
synthesis
efficiency,
advantages,
and
disadvantages
are
still
unclear.
This
review
summarizes
the
distribution
of
NAD
at
cellular
subcellular
levels,
discusses
its
biosynthetic
pathways
latest
findings
ovary,
include:
(1)
plays
distinct
roles
both
intracellularly
extracellularly,
adapting
response
requirements.
(2)
Different
differs
tissues,
synthetic
biological
utilization,
adverse
effects.
Importantly:
tryptophan
is
primarily
utilized
liver
kidneys,
posing
metabolic
risks
excess;
nicotinamide
(NAM)
indispensable
for
maintaining
levels;
nicotinic
acid
(NA)
constructs
a
crucial
bridge
between
intestinal
microbiota
host
with
diverse
functions;
riboside
(NR)
mononucleotide
(NMN)
increase
systemically
can
be
influenced
by
delivery
route,
tissue
specificity,
transport
efficiency.
(3)
The
intricately
intertwined.
They
provide
multiple
sources
techniques
synthesis,
thereby
reducing
dependence
on
single
molecule
maintain
levels.
an
excess
specific
precursor
potentially
influencing
other
pathways.
In
addition,
Protein
expression
analysis
suggest
that
tissues
may
preferentially
utilize
NAM
NMN.
These
summarize
potential
enhancing
Future
research
should
delve
into
molecular
mechanisms
intervention
strategies
different
precursors,
aiming
achieve
personalized
prevention
or
treatment
diseases,
reveal
clinical
application
value.
The
mechanisms
contributing
to
age-related
deterioration
of
the
female
reproductive
system
are
complex,
however
aberrant
protein
homeostasis
is
a
major
contributor.
We
elucidated
exceptionally
stable
proteins,
structures,
and
macromolecules
that
persist
in
mammalian
ovaries
gametes
across
lifespan.
Ovaries
exhibit
localized
structural
cell-type-specific
enrichment
both
follicular
extrafollicular
environments.
Moreover,
oocytes
harbor
panel
long-lived
including
cytoskeletal,
mitochondrial,
oocyte-derived
proteins.
exceptional
persistence
these
molecules
suggest
critical
role
lifelong
maintenance
age-dependent
tissues.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(9), С. 4680 - 4680
Опубликована: Апрель 25, 2024
The
decline
in
female
fecundity
is
linked
to
advancing
chronological
age.
ovarian
reserve
diminishes
quantity
and
quality
as
women
age,
impacting
reproductive
efficiency
the
aging
process
rest
of
body.
NAD+
an
essential
coenzyme
cellular
energy
production,
metabolism,
cell
signaling,
survival.
It
involved
various
age-related
conditions.
Hallmarks
associated
with
aging,
diseases,
metabolic
dysfunctions
can
significantly
affect
fertility
by
disturbing
delicate
relationship
between
metabolism
reproduction.
Enzymes
such
sirtuins,
PARPs,
CD38
play
roles
biology,
which
actively
consume
their
enzymatic
activities.
In
recent
years,
has
gained
much
attention
for
its
role
diseases
like
cancer,
Alzheimer’s,
cardiovascular
neurodegenerative
disorders,
highlighting
involvement
pathophysiological
processes.
However,
impact
on
reproduction
not
well
understood.
This
review
aims
bridge
this
knowledge
gap
comprehensively
exploring
complex
interplay
biology
providing
valuable
information
that
could
help
develop
plans
improve
women’s
health
prevent
issues.
