Cold Spring Harbor Perspectives in Medicine,
Год журнала:
2023,
Номер
14(6), С. a041197 - a041197
Опубликована: Дек. 5, 2023
Amit
Singh1,6,
Shepherd
H.
Schurman2,6,
Arsun
Bektas3,
Mary
Kaileh1,
Roshni
Roy1,5,
David
M.
Wilson
III4,
Ranjan
Sen1
and
Luigi
Ferrucci3
1Laboratory
of
Molecular
Biology
Immunology,
National
Institute
on
Aging,
Baltimore,
Maryland
21224,
USA
2Clinical
Research
Unit,
3Translational
Gerontology
Branch,
4Biomedical
Institute,
Hasselt
University,
Diepenbeek
3500,
Belgium
Correspondence:
ferruccilu{at}grc.nia.nih.gov
↵6
These
authors
contributed
equally
to
this
work.
↵5
Present
address:
Department
Microbiology
Emory
University
School
Medicine,
Atlanta,
Georgia
30322,
USA.
Molecular Metabolism,
Год журнала:
2023,
Номер
74, С. 101755 - 101755
Опубликована: Июнь 16, 2023
Recently,
the
hallmarks
of
aging
were
updated
to
include
dysbiosis,
disabled
macroautophagy,
and
chronic
inflammation.
In
particular,
low-grade
inflammation
during
aging,
without
overt
infection,
is
defined
as
"inflammaging,"
which
associated
with
increased
morbidity
mortality
in
population.
Emerging
evidence
suggests
a
bidirectional
cyclical
relationship
between
development
age-related
conditions,
such
cardiovascular
diseases,
neurodegeneration,
cancer,
frailty.
How
crosstalk
other
underlies
biological
mechanisms
disease
thus
particular
interest
current
geroscience
research.
The
α-Klotho
protein
(henceforth
denoted
Klotho)
has
antiaging
properties,
as
first
observed
in
mice
homozygous
for
a
hypomorphic
Klotho
gene
(kl/kl).
These
have
shortened
lifespan,
stunted
growth,
renal
disease,
hyperphosphatemia,
hypercalcemia,
vascular
calcification,
cardiac
hypertrophy,
hypertension,
pulmonary
cognitive
impairment,
multi-organ
atrophy
and
fibrosis.
Overexpression
of
opposite
effects,
extending
lifespan.
In
humans,
levels
decline
with
age,
chronic
kidney
diabetes,
Alzheimer's
disease
other
conditions.
Low
correlate
an
increase
the
death
rate
from
all
causes.
acts
either
obligate
coreceptor
fibroblast
growth
factor
23
(FGF23),
or
soluble
pleiotropic
endocrine
hormone
(s-Klotho).
It
is
mainly
produced
kidneys,
but
also
brain,
pancreas
tissues.
On
tubular-cell
membranes,
it
associates
FGF
receptors
to
bind
FGF23.
Produced
bones,
FGF23
regulates
excretion
phosphate
(phosphaturic
effect)
vitamin
D
metabolism.
Lack
results
hyperphosphatemia
hypervitaminosis
D.
With
human
function
often
deteriorates,
lowering
levels.
This
appears
promote
age-related
pathology.
Remarkably,
inhibits
four
pathways
that
been
linked
aging
various
ways:
Transforming
β
(TGF-β),
insulin-like
1
(IGF-1),
Wnt
NF-κB.
can
induce
cellular
senescence,
apoptosis,
inflammation,
immune
dysfunction,
fibrosis
neoplasia.
Furthermore,
increases
cell-protective
antioxidant
enzymes
through
Nrf2
FoxO.
accord,
preclinical
therapy
ameliorated
renal,
cardiovascular,
diabetes-related
neurodegenerative
diseases,
well
cancer.
s-Klotho
injection
was
effective,
requires
further
investigation.
Several
drugs
enhance
circulating
levels,
some
cross
blood-brain
barrier
potentially
act
brain.
clinical
trials,
increased
noted
renin-angiotensin
system
inhibitors
(losartan,
valsartan),
statin
(fluvastatin),
mTOR
(rapamycin,
everolimus),
pentoxifylline.
work,
antidiabetic
(metformin,
GLP-1-based,
GABA,
PPAR-γ
agonists)
enhanced
Klotho.
traditional
medicines
and/or
nutraceuticals
rodents,
including
astaxanthin,
curcumin,
ginseng,
ligustilide
resveratrol.
Notably,
exercise
sport
activity
review
addresses
molecular,
physiological
therapeutic
aspects
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июнь 9, 2023
Long
COVID
or
post-acute
sequelae
of
SARS-CoV-2
(PASC)
is
a
clinical
syndrome
featuring
diverse
symptoms
that
can
persist
for
months
following
acute
infection.
The
aetiologies
may
include
persistent
inflammation,
unresolved
tissue
damage
delayed
clearance
viral
protein
RNA,
but
the
biological
differences
they
represent
are
not
fully
understood.
Here
we
evaluate
serum
proteome
in
samples,
longitudinally
collected
from
55
PASC
individuals
with
lasting
≥60
days
after
onset
infection,
comparison
to
samples
symptomatically
recovered
infected
and
uninfected
individuals.
Our
analysis
indicates
heterogeneity
identified
subsets
distinct
signatures
inflammation.
Type
II
interferon
signaling
canonical
NF-κB
(particularly
associated
TNF),
appear
be
most
differentially
enriched
pathways,
distinguishing
group
patients
characterized
also
by
neutrophil
activation
signature.
These
findings
help
clarify
diversity
within
PASC,
identify
participants
molecular
evidence
highlight
dominant
pathways
have
diagnostic
therapeutic
relevance,
including
panel
propose
as
having
utility
differentiating
inflammatory
non-inflammatory
PASC.
Aging
is
a
gradual,
continuous
series
of
natural
changes
in
biological,
physiological,
immunological,
environmental,
psychological,
behavioral,
and
social
processes.
entails
the
immune
system
characterized
by
decrease
thymic
output
naïve
lymphocytes,
an
accumulated
chronic
antigenic
stress
notably
caused
infections
such
as
cytomegalovirus
(CMV),
cell
senescence
with
acquisition
inflammatory
senescence-associated
secretory
phenotype
(SASP).
For
this
reason,
due
to
SASP
originating
from
other
tissues,
aging
commonly
accompanied
low-grade
inflammation,
termed
"inflammaging".
After
decades
accumulating
evidence
regarding
age-related
processes
domain
now
appears
mature
enough
allow
integrative
reinterpretation
old
data.
Here,
we
provide
overview
topics
discussed
recent
workshop
"Aging
Chronic
Inflammation"
which
many
major
players
field
contributed.
We
highlight
advances
systematic
measurement
interpretation
biological
markers
aging,
well
their
implications
for
human
health
longevity
interventions
that
can
be
envisaged
maintain
or
improve
function
older
people.
Advances in Nutrition,
Год журнала:
2022,
Номер
13(5), С. S1 - S26
Опубликована: Май 6, 2022
The
immune
system
is
key
to
host
defense
against
pathogenic
organisms.
Aging
associated
with
changes
in
the
system,
a
decline
protective
components
(immunosenescence),
increasing
susceptibility
infectious
disease,
and
chronic
elevation
low-grade
inflammation
(inflammaging),
risk
of
multiple
noncommunicable
diseases.
Nutrition
determinant
cell
function
gut
microbiota.
In
turn,
microbiota
shapes
controls
inflammatory
responses.
Many
older
people
show
Age-related
competence,
inflammation,
dysbiosis
may
be
interlinked
relate,
at
least
part,
age-related
nutrition.
A
number
micronutrients
(vitamins
C,
D,
E
zinc
selenium)
play
roles
supporting
many
types.
Some
trials
report
that
providing
these
as
individual
supplements
can
reverse
deficits
and/or
those
insufficient
intakes.
There
inconsistent
evidence
this
will
reduce
or
severity
infections
including
respiratory
infections.
Probiotic,
prebiotic,
synbiotic
strategies
modulate
microbiota,
especially
by
promoting
colonization
lactobacilli
bifidobacteria,
have
been
demonstrated
some
biomarkers
and,
cases,
gastrointestinal
infections,
although,
again,
inconsistent.
Further
research
well-designed
well-powered
at-risk
populations
required
more
certain
about
role
modify
microbiota-host
relationship
protecting
infection,
infection.
Frontiers in Nutrition,
Год журнала:
2022,
Номер
9
Опубликована: Ноя. 1, 2022
Many
local
and
systemic
diseases
especially
that
are
leading
causes
of
death
globally
like
chronic
obstructive
pulmonary
disease,
atherosclerosis
with
ischemic
heart
disease
stroke,
cancer
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
causing
19
(COVID-19),
involve
both,
(1)
oxidative
stress
excessive
production
reactive
oxygen
species
(ROS)
lower
glutathione
(GSH)
levels,
(2)
inflammation.
The
GSH
tripeptide
(γ-
L-glutamyl-L-cysteinyl-glycine),
the
most
abundant
water-soluble
non-protein
thiol
in
cell
(1–10
mM)
is
fundamental
for
life
by
(a)
sustaining
adequate
redox
signaling
needed
to
maintain
physiologic
levels
control
processes,
(b)
limiting
tissue
damage.
activity
facilitated
activation
Kelch-like
ECH-associated
protein
1
(Keap1)-Nuclear
factor
erythroid
2-related
(Nrf2)-antioxidant
response
element
(ARE)
regulator
pathway,
releasing
Nrf2
regulates
expression
genes
controlling
antioxidant,
inflammatory
immune
system
responses.
exists
thiol-reduced
(>98%
total
GSH)
disulfide-oxidized
(GSSG)
forms,
concentrations
GSSG
their
molar
ratio
indicators
functionality
cell.
depletion
may
play
a
central
role
COVID-19
pathophysiology,
host
severity
mortality.
Therapies
enhancing
could
become
cornerstone
reduce
fatal
outcomes
increasing
prevent
subdue
these
diseases.
value
makes
paramount
research
field
biology
medicine
be
key
against
inflammation
SARS-CoV-2
infection
disease.
In
this
review,
we
emphasize
on
as
risk
(ischemic
stroke),
importance
antioxidants
(3)
significance
counteract
persistent
damaging
inflammation,
inflammaging
early
(premature)
associated
damage
caused
lack
antioxidant
defenses
younger
individuals,
(4)
new
therapies
include
restoration.
