Low grade inflammation in ageing and the role of nutrition · Philip Calder Professor of...

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

(pcc@soton.ac.uk)

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