Abstract
Older
age
and
underlying
conditions
such
as
diabetes/obesity
or
immunosuppression
are
leading
host
risk
factors
for
developing
severe
complications
from
COVID‐19
infection.
The
pathogenesis
of
COVID‐19‐related
cytokine
storm,
tissue
damage,
fibrosis
may
be
interconnected
with
fundamental
aging
processes,
including
dysregulated
immune
responses
cellular
senescence.
Here,
we
examined
effects
key
cytokines
linked
to
senescence
on
expression
SARS‐CoV‐2
viral
entry
receptors.
We
found
exposure
human
umbilical
vein
endothelial
cells
(HUVECs)
the
inflammatory
cytokines,
TNF‐α
+
IFN‐γ
a
cocktail
IL‐6,
increased
ACE2/DPP4,
accentuated
pro‐inflammatory
senescence‐associated
secretory
phenotype
(SASP),
decreased
proliferative
capacity,
consistent
progression
towards
senescence‐like
state.
IL‐6
by
itself
failed
induce
substantial
receptors
SASP‐related
genes,
while
synergy
between
initiated
positive
feedback
loop
via
hyper‐activation
JAK/STAT1
pathway,
causing
SASP
amplification.
Breaking
interactive
secretion
JAK
inhibitor
ruxolitinib
antiviral
drug
remdesivir
prevented
hyper‐inflammation,
normalized
receptor
expression,
restored
HUVECs
capacity.
This
appears
underlie
cytokine‐mediated
activation
links
hyper‐inflammation.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июнь 8, 2023
Abstract
Aging
is
characterized
by
systemic
chronic
inflammation,
which
accompanied
cellular
senescence,
immunosenescence,
organ
dysfunction,
and
age-related
diseases.
Given
the
multidimensional
complexity
of
aging,
there
an
urgent
need
for
a
systematic
organization
inflammaging
through
dimensionality
reduction.
Factors
secreted
senescent
cells,
known
as
senescence-associated
secretory
phenotype
(SASP),
promote
inflammation
can
induce
senescence
in
normal
cells.
At
same
time,
accelerates
immune
resulting
weakened
function
inability
to
clear
cells
inflammatory
factors,
creates
vicious
cycle
senescence.
Persistently
elevated
levels
organs
such
bone
marrow,
liver,
lungs
cannot
be
eliminated
leading
damage
aging-related
Therefore,
has
been
recognized
endogenous
factor
elimination
could
potential
strategy
anti-aging.
Here
we
discuss
at
molecular,
cellular,
organ,
disease
levels,
review
current
aging
models,
implications
cutting-edge
single
cell
technologies,
well
anti-aging
strategies.
Since
preventing
alleviating
diseases
improving
overall
quality
life
are
ultimate
goals
research,
our
highlights
critical
features
mechanisms
along
with
latest
developments
future
directions
providing
theoretical
foundation
novel
practical
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(23), С. 13173 - 13173
Опубликована: Дек. 6, 2021
Cellular
senescence
entails
a
state
of
an
essentially
irreversible
proliferative
arrest
in
which
cells
remain
metabolically
active
and
secrete
range
pro-inflammatory
proteolytic
factors
as
part
the
senescence-associated
secretory
phenotype.
There
are
different
types
senescent
cells,
can
be
induced
response
to
many
DNA
damage
signals.
Senescent
accumulate
tissues
organs
where
they
have
distinct
physiological
pathological
functions.
Despite
this
diversity,
all
must
able
survive
nondividing
while
protecting
themselves
from
positive
feedback
loops
linked
constant
activation
response.
This
capacity
requires
changes
core
cellular
programs.
Understanding
how
cell
undergo
extensive
their
transcriptional
programs,
metabolism,
heterochromatin
patterns,
structures
induce
common
is
crucial
preventing
cancer
development/progression
improving
health
during
aging.
In
review,
we
discuss
continuously
evolve
after
initial
highlight
unifying
features
that
define
state.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(23), С. 12641 - 12641
Опубликована: Ноя. 23, 2021
The
skin,
being
the
barrier
organ
of
body,
is
constitutively
exposed
to
various
stimuli
impacting
its
morphology
and
function.
Senescent
cells
have
been
found
accumulate
with
age
may
contribute
age-related
skin
changes
pathologies.
Natural
polyphenols
exert
many
health
benefits,
including
ameliorative
effects
on
aging.
By
affecting
molecular
pathways
senescence,
are
able
prevent
or
delay
senescence
formation
and,
consequently,
avoid
ameliorate
aging
age-associated
pathologies
skin.
This
review
aims
provide
an
overview
current
state
knowledge
in
cellular
summarize
recent
vitro
studies
related
anti-senescent
mechanisms
natural
carried
out
keratinocytes,
melanocytes
fibroblasts.
Aged
context
COVID-19
pandemic
will
be
also
discussed.
Cells,
Год журнала:
2022,
Номер
11(3), С. 359 - 359
Опубликована: Янв. 21, 2022
Acute
inflammation
is
a
physiological
response
to
injury
or
infection,
with
cascade
of
steps
that
ultimately
lead
the
recruitment
immune
cells
clear
invading
pathogens
and
heal
wounds.
However,
chronic
arising
from
continued
presence
initial
trigger,
dysfunction
signalling
and/or
effector
pathways,
harmful
health.
While
successful
ageing
in
older
adults,
including
centenarians,
associated
low
levels
inflammation,
elevated
increases
risk
poor
health
death.
Hence
has
been
described
as
one
seven
pillars
ageing.
Age-associated
sterile,
chronic,
low-grade
commonly
termed
inflammageing-it
not
simply
consequence
increasing
chronological
age,
but
also
marker
biological
ageing,
multimorbidity,
mortality
risk.
inflammageing
was
initially
thought
be
caused
by
"continuous
antigenic
load
stress",
reports
last
two
decades
describe
much
more
complex
phenomenon
involving
cellular
senescence
system.
In
this
review,
we
explore
some
main
sources
consequences
context
immunosenescence
highlight
potential
interventions.
particular,
assess
contribution
age-associated
identify
patterns
pro-
anti-inflammatory
markers
characteristic
inflammageing,
alterations
system
finally
ways
diet,
exercise,
pharmacological
interventions
can
reduce
thus,
improve
later
life
