bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 22, 2023
Summary
Macrophages
are
central
innate
immune
cells
whose
function
declines
with
age.
The
molecular
mechanisms
underlying
age-related
immunity
changes
remain
poorly
understood,
particularly
in
human
macrophages.
We
report
a
substantial
reduction
phagocytosis,
migration
and
chemotaxis
monocyte-derived
macrophages
(MDMs)
from
older
(>50
years)
compared
younger
(18-30
donors,
alongside
downregulation
of
transcription
factors
MYC
USF1
In
MDMs
young
knockdown
or
decreased
phagocytosis
altered
expression
genes
associated
these
functions,
as
well
adhesion
extracellular
matrix
remodelling.
A
concordant
dysregulation
target
was
also
seen
donors.
Furthermore,
age
loss
either
led
to
an
increased
cell
size,
morphology
reduced
actin
content.
Together,
results
define
key
drivers
MDM
functional
decline
identify
downstream
targets
improve
macrophage
ageing.
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(4), P. 114073 - 114073
Published: April 1, 2024
Macrophages
are
central
innate
immune
cells
whose
function
declines
with
age.
The
molecular
mechanisms
underlying
age-related
changes
remain
poorly
understood,
particularly
in
human
macrophages.
We
report
a
substantial
reduction
phagocytosis,
migration,
and
chemotaxis
monocyte-derived
macrophages
(MDMs)
from
older
(>50
years
old)
compared
younger
(18-30
donors,
alongside
downregulation
of
transcription
factors
MYC
USF1.
In
MDMs
young
knockdown
or
USF1
decreases
phagocytosis
alters
the
expression
associated
genes,
adhesion
extracellular
matrix
remodeling.
A
concordant
dysregulation
target
genes
is
also
seen
donors.
Furthermore,
age
loss
either
leads
to
an
increased
cell
size,
altered
morphology,
reduced
actin
content.
Together,
these
results
define
as
key
drivers
MDM
functional
decline
identify
downstream
targets
improve
macrophage
aging.
Journal of Extracellular Biology,
Journal Year:
2025,
Volume and Issue:
4(1)
Published: Jan. 1, 2025
Alzheimer's
disease
(AD)
is
an
age-related
neurodegenerative
pathology.
Brain-derived
extracellular
vesicles
(EVs)
have
been
demonstrated
to
be
implicated
in
AD
pathogenesis
by
facilitating
the
propagation
of
Tau,
amyloid-β
and
inflammatory
cytokines.
However,
impact
peripheral
EVs
(pEVs)
remains
poorly
investigated.
The
objective
our
study
was
compare
passage
pEVs
from
adults,
cognitively
healthy
elderly,
patients
through
blood-brain
barrier
(BBB),
evaluate
their
uptake
brain
assess
on
microglia
activity
using
vitro
vivo
models.
To
this
end,
were
enriched,
characterized,
fluorescently
labelled.
endothelial
bEnd.3
cells
studied
a
Transwell
device
with
either
neuronal
or
seeded
at
bottom
well.
Following
internalization
patients,
adopted
amoeboid
morphology
released
heightened
level
pro-inflammatory
cytokine
IL-6.
further
transport
across
BBB,
injected
into
blood
circulation
2-days
post-fertilization
Tg(flk1:EGFP)
zebrafish.
biodistribution
monitored
1
24
h
post-injection
confocal
microscopy.
We
that
traverse
BBB
transcytosis
subsequently
diffuse
progressively
brain.
then
internalized
radial
glial
as
seen
Tg(huc:EGFP)
Tg(gfap:EGFP)
zebrafish,
respectively.
Additional
experiments
performed
intrahippocampal
injection
mouse,
indicating
spreading
throughout
cells.
These
findings
contribute
novel
insights
fate
following
vivo,
demonstrate
for
first
time
affect
activity.
This
suggests
potential
mechanism
which
tissue
cues
may
pathogenesis.
Aging Cell,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 30, 2024
Abstract
Increasing
global
life
expectancy
motivates
investigations
of
molecular
mechanisms
aging
and
age‐related
diseases.
This
study
examines
age‐associated
changes
in
red
blood
cells
(RBCs),
the
most
numerous
host
cell
humans.
Four
cohorts,
including
healthy
individuals
patients
with
sickle
disease,
were
analyzed
to
define
age‐dependent
RBC
metabolism.
Over
15,700
specimens
from
13,757
humans
examined,
a
major
expansion
over
previous
studies
RBCs
aging.
Multi‐omics
approaches
identified
chronological
alterations
arginine
pathway
increased
utilization
older
individuals.
These
consistent
across
disease
cohorts
influenced
by
genetic
variation,
sex,
body
mass
index.
Integrating
multi‐omics
data
metabolite
quantitative
trait
loci
(mQTL)
525
diversity
outbred
mice
functionally
linked
metabolism
during
storage
vesiculation—a
hallmark
aging—and
lower
post‐transfusion
hemoglobin
increments.
Thus,
is
biomarker
organismal
aging,
suggesting
potential
new
targets
for
addressing
sequelae
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(8), P. 1890 - 1890
Published: Aug. 19, 2024
Immunosenescence,
the
gradual
deterioration
of
immune
function
with
age,
holds
profound
implications
for
our
understanding
and
management
multiple
sclerosis
(MS),
a
chronic
autoimmune
disease
affecting
central
nervous
system.
Traditionally
diagnosed
in
young
adults,
advancements
disease-modifying
therapies
increased
life
expectancy
have
led
to
growing
number
older
individuals
MS.
This
demographic
shift
underscores
need
deeper
investigation
into
how
age-related
alterations
shape
course
MS,
influencing
progression,
treatment
effectiveness,
overall
patient
outcomes.
Age-related
immunosenescence
involves
changes
such
as
shifts
cytokine
profiles,
accumulation
senescent
cells,
compromised
surveillance,
collectively
contributing
state
known
"inflammaging".
In
context
these
immunological
disturb
intricate
balance
between
inflammatory
regulatory
responses,
thereby
impacting
mechanisms
tolerance
peripheral
regulation.
paper
stands
out
by
combining
most
recent
both
pathophysiological
perspectives
on
sclerosis,
offering
cohesive
accessible
discussion
that
bridges
theory
practice,
while
also
introducing
novel
insights
underexplored
concepts
therapy
discontinuation
latest
senolytic,
neuroprotective,
remyelination
therapies.
Enhancing
complexities
will
guide
tailored
approaches
MS
management,
ultimately
improving
clinical
outcomes
affected
individuals.
Биохимия,
Journal Year:
2024,
Volume and Issue:
89(5), P. 818 - 832
Published: Nov. 14, 2024
Tumor-associated
macrophages
(TAMs)
are
an
important
component
of
the
tumor
microenvironment
(TME)
and
most
abundant
population
immune
cells
infiltrating
a
tumor.
TAMs
can
largely
determine
direction
anti-tumor
response.
promote
it
or,
conversely,
contribute
to
formation
immunosuppressive
TME
that
allows
tumors
evade
control.
Through
interactions
with
or
other
in
microenvironment,
as
result
action
anti-cancer
therapy,
enter
senescence.
In
this
review,
we
have
attempted
summarize
information
available
literature
on
role
senescent
tumors.
With
recent
development
senolytic
therapeutic
strategies
aimed
at
removing
from
organism.
It
seems
discuss
functions
potential
drugs
reprogramming
enhance
response
improve
efficacy
cancer
treatment.
Immunity & Ageing,
Journal Year:
2024,
Volume and Issue:
21(1)
Published: July 3, 2024
Abstract
Background
The
function
of
polymorphonuclear
neutrophils
(PMNs)
decreases
with
age,
which
results
in
infectious
and
inflammatory
complications
older
individuals.
underlying
causes
are
not
fully
understood.
ATP
release
autocrine
stimulation
purinergic
receptors
help
PMNs
combat
microbial
invaders.
Excessive
extracellular
interferes
these
mechanisms
promotes
PMN
responses.
Here,
we
studied
whether
dysregulated
signaling
contributes
to
their
dysfunction
Results
Bacterial
infection
C57BL/6
mice
resulted
exaggerated
activation
that
was
significantly
greater
old
(64
weeks)
than
young
animals
(10
weeks).
In
contrast
animals,
were
unable
prevent
the
systemic
spread
bacteria,
resulting
lethal
sepsis
mortality
younger
counterparts.
We
found
levels
plasma
increased
age
that,
along
accumulation
ATP,
became
increasingly
primed.
Stimulation
formyl
peptide
those
primed
triggered
responses
more
pronounced
animals.
However,
bacterial
phagocytosis
killing
by
lower
mice.
These
age-dependent
dysfunctions
correlated
a
decrease
enzymatic
activity
ATPases
convert
adenosine.
depend
on
divalent
metal
ions,
including
Ca
2+
,
Mg
Zn
depletion
ions
blocked
hydrolysis
formation
adenosine
human
blood,
dysregulation
functions
equivalent
observed
response
aging.
Conclusions
Our
findings
suggest
impaired
dysregulates
conclude
strategies
aimed
at
restoring
ATPase
may
offer
novel
therapeutic
opportunities
reduce
immune
dysfunction,
inflammation,
patients.
