Mortality Experts Meeting Staple Inn Hall 3 March 2008

Living Ever Longer?

Tom Kirkwood

Director, Institute for Ageing and HealthNewcastle University

The Continuing Increase in Life Expectancy

UN estimate 1980

UN estimate 1990

UN estimate 2000

Oeppen & Vaupel Science 2002

Declining early/mid-life mortality Declining later-life mortality

The Challenges for Mortality Research

• Life is getting longer already – do we understand why?

• What is the likelihood of further increases in life span?

• What is likely to happen to age-related health, quality of life and capacity for independent living?

Key Questions about Ageing

• Why does ageing occur?

• Is there a limit to the human life span?

• Do longer lives mean more diseases?

Progress Through the Stages of Life

Then

Now

20 8040 60 Age

Age

Su

rviv

al

Period of longevity assured by maintenance and repair

Wild

Protected

DISPOSABLE SOMA THEORY

Kirkwood Nature 1977

Age-related Frailty, Disability, and Disease

Accumulation of Cellular Defects

Random Molecular Damage

The Ageing Process Kirkwood Cell 2005

STRESS ENVIRONMENTBAD

FOOD

GOOD LIFESTYLE

GOOD FOOD

INFLAMMATION ANTI-INFLAMM.

Human Ageing is Malleable

By decreasing exposure to damage– Improved nutrition– Healthy lifestyle– Supportive environment

By enhancing natural mechanisms for protection and repair– Enhanced nutrition– Novel drugs, stem cell therapies, etc

Factors Influencing Longevity and Health Span

Genes Nutrition Lifestyle Environment Socioeconomic status Attitude Chance

These factors and their interactions are being studied in the Newcastle 85+ Study; a 5-year prospective study of biological, clinical and psychosocial factors associated with healthy ageing funded by MRC/BBSRC.

Genetic Heritability of Human LifespanCournil & Kirkwood Trends in Genetics 2001

Twin Studies• McGue et al (1993) 0.22• Herskind et al (1996) 0.25• Ljungquist et al (1998) <0.33

Traditional Family Studies• Philippe (1978) 0-0.24• Bocquet-Appel & Jakobi (1990) 0.10-0.30• Mayer (1990) 0.10-0.33• Gavrilova et al (1998) 0.18-0.58• Cournil et al (2000) 0.27

Genes account for 25% of what determines longevity

• High intakes of vegetables, fruits and cereals.

• Moderate to high intake of fish.

• Low intake of meat.

• Low intake of saturated fatty acids.

• High intake of monounsaturated fatty acids (olive oil).

• Low to moderate intake of dairy products, principally cheese and yoghurt.

• Modest intake of alcohol (mostly wine).

Trichopoulou A et al. (2005) BMJ 330, 991-997

EPIC-elderly Study Protocol

76,707 men and women aged 60+

No CHD, stroke or cancer at enrolment

Median follow up 89 months (4047 deaths)

Adherence to Mediterranean diet assessed on 10-point scale:0 (poor)…9 (high)

2 unit increment results in 8% reduction of overall mortality

Do longer lives mean more diseases?

For many important diseases, age is the largest single ‘risk factor’.

Understanding why aged cells and organs are more vulnerable to pathology will open new paths to prevention and cure.

At present, we have many medical research institutes but very few of these include research on the science of intrinsic ageing.

The coming decades are likely to see greatly expanded research on the mechanisms underpinning both normal ageing and age-related diseases.

Disease A

Disease B

Disease C

‘Upstream’ ‘Downstream’

Pathways to Age-Related Disease

Pop

ulat

ion

num

bers

Healthy Unhealthy condition

Targeting for Healthy Ageing

Target Population for Drugs, etc

Adapted from: Green and van der Ouderaa Nature Pharmacogenomics 2003

Target Population for Nutrition/Lifestyle

NowFuture

Beating the Biological Clock

Chronological Ageing

Biological Ageing

‘Wrong’ lifestyle•Excess calorie intake•High saturated fats•Low micro-nutrients•Too little exercise•Poor glucose tolerance•Stress•Smoking

‘Right’ lifestyle•Energy balance•Maintain glucose sensitivity•Low saturated fats•Rich micro-nutrient diet•High exercise level•Low to moderate stress

“If I’d known I was going to live this long, I’d have taken better care of myself”

US comedian Eubie Blake on his 100th birthday

Today and Beyond

Understanding the future of mortality patterns calls for an multi-disciplinary approaches.

Other disciplines have much to learn from the actuarial profession, and vice versa.

How to take forward the building of further bridges?