The demographic transition

0

10

20

30

40

50

60

0 20 40 60 80 100 120 140

Years

Bir

th o

r d

eath

rat

e p

er 1

000

per

yr

pre-modern industrializing mature industrial

post industrial

Deaths

Births

Population

Lifestyle diseases:the burden of choice?

CH

RIS

TO

PH

ER

DY

E

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

Lifestyle diseases:the burden of choice?

CH

RIS

TO

PH

ER

DY

E

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

Diseases of civilization?

Western disease paradigm?

Diseases of affluence?

Where 60 million people die double burden of disease in low-income countries

0

2

4

6

8

Communicable,pregnancy,

nutrition

Non-communicable

Injuries

Dea

ths

per

mill

ion

po

pu

lati

on

Low-middle income

High income

Chronic diseases?Non-communicable diseases?

Cardiovascular disease: heart disease, stroke

CancerChronic respiratory

diseasesDiabetes

Top 12 causes of death: Africa/S Asia

0

2 000

4 000

6 000

8 000

10 000

Dea

ths

('00

0s i

n 2

001) going down slowly

going up

Top 12 causes of death: W Europe/N America

0

1 000

2 000

3 000

Dea

ths

('00

0s i

n 2

001)

Diseases of longevity?

Growth: 1 extra year in 4

40

50

60

70

80

90

100

1820 1845 1870 1895 1920 1945 1970 1995 2020 2045 2070

Life expectancy

Maxima estimated inyear given

Inexorable growth in life expectancy?women in leading countries

source: Oeppen 2002

Most years of life lost to to cancer, heart disease, stroke are in people 45+

0

2000

4000

6000

8000

10000

12000

0-4 5-14 15-29 30-44 45-59 60-69 70-79 80+

Age class (years)

To

tal y

ea

rs h

ea

lth

y li

fe lo

st Cardiovascular

diseaseCancers

0

2

4

6

8

10

12

14

16

18

20

2-5 6-11 12-19

Age class (years)

Pe

rce

nta

ge

ov

erw

eig

ht

1963-65

1971-74

1976-80

1988-94

1999-00

2001-02

2003-04

Obesity steeply rising among children in USA since 1980 (CDC data)

Chronic, non-communicable diseases in long-lived populations

Why do we age and

die?

Median age menopause

≈ 50 years

Life begins at 40? Conception in women, England & Wales, 2005

0

20

40

60

80

100

120

140

Under16

Under18

Under20

20–24 25–29 30–34 35–39 40 andover

Co

nce

pti

on

s p

er 1

000

wo

men

Menopause age 50

Why we age and dieKirkwood's "disposable soma"

Evolution acts through reproduction Survival depends on maintenance, which

is costly after reproduction

A lifelong accumulation of faults…

0

20

40

60

80

100

0 20 40 60 80 100

Age (years)

Pe

rce

nt

su

rviv

ing

Zen 禅 and the art of metabolic maintenance?

Survival of hunter-gatherers and Japanese

Fixing the faults?"in the end costs exceed benefits"

Doug Wallace U California

"…as each life-limiting process is countered, some other process will become limiting"

What causes of disease can be modified?

Ischemic heart disease: main risk factors 84% explained in high-income countries

-20

0

20

40

60

Cholest

erol

Blood p

ressu

re

Overwei

ght

Smoki

ng

Physic

al in

activ

ity

Low fruit/

veg d

iet

Air pol

lutio

n

Alcohol

Att

rib

uta

ble

fra

ctio

n (

%)

Stroke: main risk factors 68% explained in high-income countries

-20

0

20

40

60

Blood p

ress

ure

Cholest

erol

Smoki

ng

Overw

eight

Low fruit/

veg d

iet

Physic

al in

activ

ity

Urban

air

pollutio

n

Alcohol

Att

rib

uta

ble

fra

ctio

n (

%)

Trans fat increased risk of heart disease in 20,000 women followed for 20 years

-0.4 -0.2 0 0.2 0.4 0.6 0.8

Polyunstaturatedfat

Trans fat

lower risk I higher risk

1766 instances of heart attack

Trans fats 50 years of research to get the label on the tin

Variation in life expectancy in England

Smoking deaths are higher in northern England and London

Much of the variation in mortality betwen social classes is due to smoking

0

10

20

30

40

50

60

high middle low high middle low

Ris

k o

f dyi

ng

at a

ge

35-6

9 yr

s

Othercauses

Smoking

social class education

England & Wales Poland

Source: P Jha Lancet

2006

"I have taken more out of alcohol than alcohol has taken out of me"

…only two before

breakfast

Alcohol lowers risk of coronary heart disease in men with healthy lifestyles

0

0.2

0.4

0.6

0.8

1

Alcohol (grams per day)

Rel

ativ

e ri

sk h

eart

att

ack

(MI)

- diet

- smoking

- activity

- weight

Source: Arch Intern Med v166,

p2145, 2006

1/2 to 2 drinks per day

CVD: can all major risks can be reduced on a large scale?

What causes of disease

cannot be modified?

All cancers: risk factors 37% explained in high income countries

-20

0

20

40

60

Smoki

ng

Alcohol

Overw

eight

Low fruit/

veg d

iet

Urban

air

pollutio

n

Unsafe

sex

Physic

al in

activ

ity

Att

rib

uta

ble

fra

ctio

n (

%)

Lung cancer: smoking 86%

Cancer: a glimpse of immortality

Cancerwhen

somatic cells

revert by accident to germ-like cells

Immortal germ cells Mortal somatic cells

Cancer cells

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

"Dozens of new cancer genes found"Nature, 8 March 2007

US Cancer Incidence Trends (1975-2003) for Top 10 sites

Men

1975-92 increase 1992-95 decrease 1995-03 stable

Women

1975-79 stable 1979-03 increase

1975 2003

Genetic differences account for up to ¼ variation in life span

Danish, Finnish, Swiss twinsBorn 1870-191020,502 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

Genetic differences account for up to ¼ variation in life span

Weak correlation in longevity of twins

How much choice do we really

have?

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

"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"

Maltesers: not lighter than airBritons 2nd most obese in Europe

Percent population with Body Mass Index 30+ EU countries

0

5

10

15

20

25

Mal

ta UK

Germ

any

Hungary

Lithuan

ia

Latvi

a

Czech

Rep

ublic

Portugal

Finla

nd

Slova

kia

Estonia

Irela

ndSpai

n

Bulgar

ia

Cypru

s

Slove

nia

Icel

and

Poland

Belgiu

m

Greec

e

Sweden

Denm

ark

France

Nether

lands

Austria

Roman

iaIta

ly

Switzer

land

Norway

% p

op

ula

tio

n o

bes

e (B

MI 3

0+)

UK population ranked #2

Obesity in Englandhighest in midlands and north

Lowest in:

London

South east

South west

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

The "obesogenic environment" 10 other possible explanations

1. Not enough sleep (obesity <=> sleep)2. Warm houses demand less personal energy 3. Less smoking4. Overweight mothers have overweight children5. Overweight mothers have more children6. Older mothers have overweight children7. Older people are heavier8. Drugs (hypertension etc) induce weight gain?9. Environmental pollution (hormone

interference)10.Like (fat) marrying like (fat)

Life before birth:Fetal 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

"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 stunted…serious intergenerational effects" James Commission 2000

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

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 smokingbut 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"