Senescent
cells
accumulate
in
aging
tissues,
impairing
their
ability
to
undergo
repair
and
regeneration
following
injury.
Previous
research
has
demonstrated
that
targeting
tissue
senescence
with
senolytics
can
enhance
by
selectively
eliminating
SnCs
specific
aged
tissues.
In
this
study,
we
focused
on
senescent
skin
mice
assess
the
effects
subsequent
wound
healing.
We
applied
ABT-263
directly
of
24-month-old
over
a
5-day
period.
Following
topical
ABT-263,
decreased
gene
expression
markers
p16
p21,
accompanied
reductions
SA-β-gal-
p21-positive
compared
DMSO
controls.
However,
also
triggered
temporary
inflammatory
response
macrophage
infiltration
skin.
Bulk
RNA
sequencing
ABT-263-treated
revealed
prompt
upregulation
genes
associated
healing
pathways,
including
hemostasis,
inflammation,
cell
proliferation,
angiogenesis,
collagen
synthesis,
extracellular
matrix
organization.
Aged
pre-treated
exhibited
accelerated
closure.
conclusion,
effectively
reduced
several
skin,
thereby
priming
for
improved
This
enhancement
may
be
attributed
ABT-263-induced
senolysis
which
turn
stimulates
involved
remodeling
pathways.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 19, 2024
Abstract
Senescent
cells
(SnC)
accumulate
in
aging
tissues,
impairing
their
ability
to
undergo
repair
and
regeneration
following
injury.
Previous
research
has
demonstrated
that
targeting
tissue
senescence
with
senolytics
can
enhance
by
selectively
eliminating
SnCs
specific
aged
tissues.
In
this
study,
we
focused
on
SnC
skin
mice
assess
the
effects
subsequent
wound
healing.
We
applied
ABT-263
directly
of
24-month-old
over
a
5-day
period.
Following
topical
ABT-263,
decreased
gene
expression
senescent
markers
p16
p21,
accompanied
reductions
SA-β-gal
p21-positive
compared
DMSO
controls.
However,
also
triggered
temporary
inflammatory
response
macrophage
infiltration
skin.
Bulk
RNA
sequencing
ABT-263-treated
revealed
prompt
upregulation
genes
associated
healing
pathways,
including
hemostasis,
inflammation,
cell
proliferation,
angiogenesis,
collagen
synthesis,
extracellular
matrix
organization.
Aged
pre-treated
exhibited
accelerated
closure.
conclusion,
effectively
reduced
several
skin,
thereby
priming
for
improved
This
enhancement
may
be
attributed
ABT-263-induced
senolysis
which
turn
stimulates
involved
remodeling
pathways.
There
is
a
growing
need
to
better
characterise
senescent
cells
in
the
CNS
and
retina.
The
recently
published
SenMayo
gene
panel
was
developed
identify
transcriptomic
signatures
of
senescence
across
multiple
organ
systems,
but
retina
not
included.
While
other
approaches
have
identified
retina,
these
largely
focused
on
experimental
models
young
animals.
We
therefore
conducted
detailed
single-cell
RNA-seq
analysis
cell
populations
different
aged
mice
compared
with
five
comprehensive
human
mouse
brain
transcriptome
datasets.
Transcriptomic
were
most
apparent
retinal
glial
cells,
IL4,
13
10
AP1
pathway
being
prominent
markers
involved.
Similar
levels
transcriptional
observed
glia
old
mice,
whereas
showed
significantly
increased
enrichment
scores
advancing
age.
Senescent
cells
accumulate
in
aging
tissues,
impairing
their
ability
to
undergo
repair
and
regeneration
following
injury.
Previous
research
has
demonstrated
that
targeting
tissue
senescence
with
senolytics
can
enhance
by
selectively
eliminating
SnCs
specific
aged
tissues.
In
this
study,
we
focused
on
senescent
skin
mice
assess
the
effects
subsequent
wound
healing.
We
applied
ABT-263
directly
of
24-month-old
over
a
5-day
period.
Following
topical
ABT-263,
decreased
gene
expression
markers
p16
p21,
accompanied
reductions
SA-β-gal-
p21-positive
compared
DMSO
controls.
However,
also
triggered
temporary
inflammatory
response
macrophage
infiltration
skin.
Bulk
RNA
sequencing
ABT-263-treated
revealed
prompt
upregulation
genes
associated
healing
pathways,
including
hemostasis,
inflammation,
cell
proliferation,
angiogenesis,
collagen
synthesis,
extracellular
matrix
organization.
Aged
pre-treated
exhibited
accelerated
closure.
conclusion,
effectively
reduced
several
skin,
thereby
priming
for
improved
This
enhancement
may
be
attributed
ABT-263-induced
senolysis
which
turn
stimulates
involved
remodeling
pathways.
