The demographic transition

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The demographic transition
60
mature
post
pre-modern
industrializing
industrial
industrial
50
40
Births
Population
30
Birth or death rate per 1000 per yr
20
Deaths
10
0
0
20
40
60
80
100
120
140
Years
2
Lifestyle diseases the burden of choice?
CHRISTOPHER DYE

• What are "lifestyle" diseases?
• Disease burden we suffer by choice?
• The agony of reversing the choice?

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Lifestyle diseases the burden of choice?
CHRISTOPHER DYE

• Diseases of civilization
• Western disease paradigm
• Diseases of affluence
• Chronic diseases
• Non-communicable diseases
• Diseases of longevity

4
Diseases of civilization?
5
Western disease paradigm?
6
Diseases of affluence?
7
Where 60 million people die
double burden of disease in low-income countries
8
Low-middle income
High income
6
Deaths per million population
4
2
0
Communicable,
Non-
Injuries
pregnancy,
communicable
nutrition
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Chronic diseases?Non-communicable diseases?

• Cardiovascular disease heart disease, stroke
• Cancer
• Chronic respiratory diseases
• Diabetes

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going down slowly
going up
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11
Diseases of longevity?
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Chronic, non-communicable diseases in long-lived
populations
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Why do we age and die?
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Life begins at 40?
Conception in women, England Wales, 2005
140
120
Menopause age 50
Median age menopause 50 years
100
80
Conceptions per 1000 women
60
40
20
0
Under
Under
Under
2024
2529
3034
3539
40 and
16
18
20
over
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Why we age and dieKirkwood's "disposable soma"

• Evolution acts through reproduction Survival
  depends on maintenance, which is costly after
  reproduction

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A lifelong accumulation of faults
19
Zen ? and the art of metabolic maintenance?
Survival of hunter-gatherers and Japanese
100
80
60
Percent surviving
40
20
0
0
20
40
60
80
100
Age (years)
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Fixing the faults?"in the end costs exceed
benefits"
"as each life-limiting process is countered,
some other process will become limiting"
Doug Wallace U California
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What causes of disease can be modified?
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Trans fats 50 years of research to get the label
on the tin
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Variation in life expectancy in England
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Smoking deaths are higher in northern
England and London
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"I have taken more out of alcohol than alcohol
has taken out of me"
only two before breakfast
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CVD can all major risks can be reduced on a
large scale?
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What causes of disease cannot be modified?
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Cancer a glimpse of immortality

• Cancerwhen somatic cells revert by accident to
  germ-like cells

Immortal germ cells
Mortal somatic cells
Cancer cells
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"Dozens of new cancer genes found"Nature, 8
March 2007

• Cancer caused by genetic (DNA) defects
• 500 genes in 200 kinds of cancer
• The bad news
• More new cancer genes (100) than expected ( 10)
  
• ..and the worse news
• Cancer genomes carry many unique abnormalities,
  not all mutations contribute equally
• Diverse, unpredictable, causes

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US Cancer Incidence Trends (1975-2003) for Top
10 sites
1975 2003
Men 1975-92 increase 1992-95 decrease 1995-03
stable Women 1975-79 stable 1979-03 increase
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Genetic differences account for up to ¼ variation
in life span

• Danish, Finnish, Swiss twins
• Born 1870-1910
• 20,502 same sex pairs
• No genetic influence on longevity before
• age 60
• Chance of living to be 100 in
• Woman whose sister lives to 100
• 4 vs 1
• Man whose sister lives to 100
• 0.4 vs 0.1

K Christensen
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Genetic differences account for up to ¼ variation
in life span

• Weak correlation in longevity of twins

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How much choice do we really have?
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What to pack for the "Fantastic Voyage"?
3 bridges to immortality Bridge One current
knowledge to slow down the aging process Bridge
Two advances in biotechnology to stop disease and
reverse aging Bridge Three (nano)technology to
create man-machine interface, expanding physical
and mental capabilities
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"Moneypenny, I'm to eliminate all free
radicals" J Bond (Goldfinger)

• Free radicals by-products of respiration,
  stabilized by oxidizing (and damaging) proteins,
  carbohydrates, fats, DNA
• Antioxidants in fruits/vegetables, prevent
  oxidation
• Fantastic Voyage the more supplements the better
• Science "stick to tea, fruit, veg, wine in
  moderation until more evidence"

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Maltesers not lighter than airBritons 2nd most
obese in Europe
Percent population with Body Mass Index 30 EU
countries
25
UK population ranked 2
20
15
population obese (BMI 30)
10
5
0
UK
Italy
Malta
Spain
Latvia
Ireland
Cyprus
Poland
France
Austria
Finland
Estonia
Iceland
Greece
Norway
Sweden
Hungary
Portugal
Slovakia
Bulgaria
Belgium
Romania
Germany
Slovenia
Lithuania
Denmark
Switzerland
Netherlands
Czech Republic
42
Obesity in Englandhighest in midlands and north
Lowest in London South east South west
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The obesity epidemic too much food, too little
exercise?

• Why the "Big Two" just won't do
• "evidence that they are the main cause of the
  epidemic - or that halting them would reverse it
  - is "largely circumstantial" (20 obesity
  experts)
• "We threw tens of millions of dollars at the best
  investigators in the world - and they found
  absolutely no effect" (David Allison, University
  of Alabama)
• International Journal of Obesity 2006

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The "obesogenic environment" 10 other possible
explanations

• Not enough sleep (obesity ltgt sleep)
• Warm houses demand less personal energy
• Less smoking
• Overweight mothers have overweight children
• Overweight mothers have more children
• Older mothers have overweight children
• Older people are heavier
• Drugs (hypertension etc) induce weight gain?
• Environmental pollution (hormone interference)
• Like (fat) marrying like (fat)

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Life before birthFetal origins of adult disease
David Barker's "Early Origins Hypothesis" (1986)
Links low birth weight to increased risk of
chronic disease in later life
Osteoporosis, chronic obstructive lung disease,
polycystic ovary syndrome, cancers of the breast,
ovary and prostate, and mental disorders
including schizophrenia and depression
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"Poverty that lays eggs"Zimbabwe
"poverty passes from one generation to another,
as if the offspring sucks it from the mother's
breast" Uganda
"90m children stuntedserious intergenerational
effects" James Commission 2000
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Status syndromeLow social status linked to high
mortality

• Shishehbor (JAMA 2006)
• 30,000 patients with heart disease in Ohio, USA,
  1990-2002
• Over 2000 deaths
• People with low socio-economic status had
  abnormal heart rate recovery, death rate higher
  by 22-42
• Lack of control, low participation

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Lifestyle (chronic) diseases a few tough choices

• As lifespan increases, burden of ill health
  shifts to "chronic" diseases (CVD, cancer)
• though chronic diseases are rising in young
  people too, and infections have not disappeared
• There are "modifiable" risk factors, esp. for
  CVD, including diet, exercise and smoking
• but some risks are hard to change (addiction),
  or beyond personal control (society, long time
  scales)
• Chronic disease (esp. cancer) is linked to aging,
  through lifelong accumulation of faults
• no gain without pain, no quick-fix, no elixir
  for the "Fantastic Voyage"