Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation
eLife,
Journal Year:
2024,
Volume and Issue:
13
Published: Jan. 3, 2024
Over
the
past
several
decades,
a
trend
toward
delayed
childbirth
has
led
to
increases
in
parental
age
at
time
of
conception.
Sperm
epigenome
undergoes
age-dependent
changes
increasing
risks
adverse
conditions
offspring
conceived
by
fathers
advanced
age.
The
mechanism(s)
linking
paternal
with
epigenetic
sperm
remain
unknown.
is
shaped
compartment
protected
blood-testes
barrier
(BTB)
known
deteriorate
Permeability
BTB
regulated
balance
two
mTOR
complexes
Sertoli
cells
where
complex
1
(mTORC1)
promotes
opening
and
2
(mTORC2)
its
integrity.
We
hypothesized
that
this
also
responsible
for
epigenome.
To
test
hypothesis,
we
analyzed
reproductive
outcomes,
including
DNA
methylation
transgenic
mice
cell-specific
suppression
mTORC1
(
Rptor
KO)
or
mTORC2
Rictor
KO).
accelerated
aging
methylome
resulted
phenotype
concordant
older
age,
decreased
testes
weight
counts,
increased
percent
morphologically
abnormal
spermatozoa
mitochondrial
copy
number.
Suppression
shift
opposite
associated
physiological
–
rejuvenation
mild
parameters.
These
results
demonstrate
first
regulates
rate
aging.
Thus,
pathway
may
be
used
as
novel
target
therapeutic
interventions
rejuvenate
advanced-age
fathers.
Language: Английский
Mechanistic target of rapamycin/blood-testes barrier mechanism mediates acceleration of sperm epigenetic aging by environmental factors
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
Abstract
Our
previous
research
suggested
that
mechanistic
target
of
rapamycin
(mTOR)/blood-testis
barrier
(BTB)
mechanism
is
involved
in
the
regulation
rates
epigenetic
aging
sperm,
where
increased
activity
mTORC1
opens
BTB
and
accelerates
mTORC2
produces
opposite
results
–
increases
integrity
rejuvenates
sperm
epigenome.
In
present
study,
we
use
our
newly
developed
clock
model
to
investigate
whether
mTOR/BTB
reprogramming
mice
exposed
heat
stress
(HS)
cadmium
(Cd).
findings
show
both
mTOR-dependent
disruption
caused
by
HS
mTOR-independent
due
Cd
exposure
accelerate
aging,
resulting
similar
changes
DNA
methylation
patterns.
These
suggest
a
novel
molecular
pathway
through
which
environmental
stressors
influence
this
may
be
relevant
broad
range
factors,
including
environmental,
lifestyle,
dietary,
health
influences.
Language: Английский
The Sertoli Cell as a Target for Toxicants
Elsevier eBooks,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Language: Английский
Exploring the Mechanisms of Testicular Aging: Advances in Biomarker Research
Aging and Disease,
Journal Year:
2025,
Volume and Issue:
unknown, P. 0 - 0
Published: Jan. 1, 2025
Aging
biomarkers
quantify
aging
progression
and
provide
actionable
targets
for
therapeutic
interventions
to
mitigate
age-related
decline.
This
review
synthesizes
emerging
evidence
on
testicular
biomarkers,
focusing
cellular
senescence
(Leydig,
Sertoli,
endothelial
cells),
protein
homeostasis
disruption,
mitochondrial
dysfunction,
germ
stem
cell
depletion,
sperm
telomere
length,
epigenetic
alterations,
oxidative
stress,
inflammation,
gut
microbiota
dysbiosis.
We
propose
that
serves
as
a
critical
nexus
linking
reproductive
decline
with
systemic
processes,
its
pathological
being
quantifiable
through
specific
including
the
Leydig,
cells,
INSL3,
ribosomal
RPL39L,
relative
length
translocator
protein,
sialic
acid.
By
bridging
paradigms
testis-specific
mechanisms,
we
emphasize
urgency
identify
organ-selective
targeted
interventions,
advancing
strategies
preserve
male
fertility
address
population
challenges.
Language: Английский
Revealing the Landscape Crosstalk Between Reproductive System and Organs Aging
The FASEB Journal,
Journal Year:
2025,
Volume and Issue:
39(8)
Published: April 27, 2025
ABSTRACT
The
reproductive
system
is
a
vital
component
of
the
human
body.
In
modern
society,
due
to
various
socio‐economic
reasons,
an
increasing
number
couples
are
choosing
postpone
childbearing.
Research
into
impact
aging
on
becoming
increasingly
important.
As
people
age,
there
decline
in
across
levels,
from
testes
males
spermatogonia
cells,
and
ovaries
females
oocytes.
not
only
affects
itself
but
also
has
implications
for
other
organs
systems
Conversely,
can
damage
system.
This
review
organizes
changes
that
occur
within
as
result
focuses
interactions
between
systems.
Additionally,
this
summarizes
current
therapies
aimed
at
delaying
aging,
which
may
provide
insights
future
interventions
targeting
Language: Английский
Molecular Basis of Sperm Methylome Response to Aging and Stress
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 15, 2024
ABSTRACT
Changes
in
the
sperm
epigenome
induced
by
age
and/or
stressors
often
follow
common
unexplained
patterns
affecting
genes
responsible
for
embryonic
development
and
neurodevelopment.
The
stochastic
epigenetic
variation
(SEV)
hypothesis
proposes
that
response
to
naturally
variable
methylation
regions
(VMRs)
associated
with
morphogenic
increase
diversify
phenotypes
improve
chances
of
survival
genetic
lineage.
Here,
we
test
predictions
from
SEV
using
mouse
rat
DNA
other
-omics
data.
We
demonstrate
context
determines
methylome
various
factors
rather
than
timing
these
factors.
propose
a
model
explaining
age/stress-dependent
shifts
VMRs
an
asymmetric
regions.
Because
increases
age,
may
be
characterized
as
acceleration
aging.
Language: Английский