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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?
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.
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