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NIHR Southampton
Biomedical Research Centre in nutrition
The NIHR Southampton Biomedical Research Centre in nutrition is funded by the National Institute for Health Research (NIHR) and is a partnership
between University Hospital Southampton NHS Foundation Trust and the University of Southampton
Low grade inflammation in ageing
and the role of nutrition
Philip Calder
Professor of Nutritional Immunology
University of Southampton
Southampton
FoodMatters live, London, November 2018
Where inflammation is
uncontrolled or excessive or
continues unabated tissue damage
and metabolic changes occur
Time
Inte
nsit
y o
f th
e
infl
am
mato
ry r
esp
on
se
Initiation
phase
Resolution
phase
Time
Inte
nsit
y o
f th
e
infl
am
mato
ry r
esp
on
se
Initiation
phase
SELF-LIMITING INFLAMMATION
Loss of
resolution
CHRONIC INFLAMMATION
Time
Inte
nsit
y o
f th
e
infl
am
mato
ry r
esp
on
se
Initiation
phase
Resolution
phase
Time
Inte
ns
ity o
f th
e
infl
am
mato
ry r
esp
on
se
Initiation
phase
SELF-LIMITING INFLAMMATION
Loss of
resolution
CHRONIC INFLAMMATION
LOW GRADE
Chronic low grade inflammation
Linked with increased risk of non-communicable diseases
(these disease are also linked with lifestyle and with age)
Inflammatory markers increase with age
-> termed inflammageing
Calder et al. (2017) Ageing Research Reviews 40, 95-119
How might dietary components influence inflammation?
Pro-oxidant
Trigger of pro-inflammatory
signalling cascades
(e.g. allergens, SFA)
Precursor of anti-inflammatory/pro-resolving
mediators (e.g. n-3 FA)
Antioxidant (e.g. several vitamins,
many polyphenolics)
LESS MORE
Negative modulator of pro-inflammatory
signalling cascades
(e.g. many polyphenolics, n-3 FA)
Positive modulator of
pro-inflammatory signalling cascades
“Improve” gut microbiota (e.g. some fibres) Precursor of pro-inflammatory
molecules (e.g. ARA and PGs)
Chrysohoou et al. (2004) J. Am. Coll. Cardiol. 44, 152-158
Dai et al. (2008) Circulation 117, 169-175
(n = 3000)
Lopez-Garcia et al. (2004) Am. J. Clin. Nutr. 80, 1029-1035
(n = 732)
These studies suggest that a “healthy” diet is
associated with lower concentrations of
inflammatory markers in the bloodstream
The opposite must also be true i.e. an
“unhealthy” diet must be associated with
higher concentrations of inflammatory markers
in the bloodstream
Lopez-Garcia et al. (2004) Am. J. Clin. Nutr. 80, 1029-1035
(n = 732)
Can changing diet alter inflammation?
Estruch et al. (2006) Ann. Intern. Med. 145, 1-11 Intervention; 3 months; n = 275/group; 90% overweight or obese; 50% diabetic
CRP
Association studies show a higher intake of …
•Whole grains
•Vegetables and fruits
•Fish
•Nuts
•Olive oil
… is associated with lower inflammation
The pattern of bacteria within
the human gut changes with age
Hopkins et al. (2001) Gut 48, 198-205
Community dwelling adults by age (y) Community dwelling vs residential care
(months in care)
Calder et al. (2017) Ageing Res. Rev. 40, 95-119
“New” paradigm
Inflammation has two phases :
initiation and resolution
Initiation
phase
Resolution
phase
TIME
Initiation
phase
Resolution
phase
TIME
What chemicals are present
during the resolution phase?
New families of lipid mediators identified:
• Resolvins
• Protectins
• Maresins
Tissue injury
Microbes Acute inflammation
Chronic inflammation
Tissue damage
Persistent infection
Inflammatory disease
Resolution
Tissue repair
Healing
Homeostasis
Omega-3
derived pro-
resolving
mediators
Before placebo
After placebo
Before fish oil
After fish oil
• Inflammation is a key part of defence; it should self
resolve
• Chronic inflammation is a recognised contributor to
pathology
• Chronic low grade (silent) inflammation is an important
contributor to common NCDs
• Chronic low grade inflammation is a feature of ageing – it
likely contributes to age-related NCD risk
• Healthy diets and their constituent foods are linked to
lower levels of inflammatory markers (cohort studies,
RCTs)
• Gut microbiota changes with ageing and may be a link
between diet and inflammation
• Omega-3 fatty acids (EPA and DHA) are precursors of
pro-resolving mediators
Summary
