Transcript Slide 1

Birth or death rate per 1000 per yr
The demographic transition
60
pre-modern
mature
industrial
industrializing
post
industrial
50
40
Births
Population
30
20
Deaths
10
0
0
20
40
60
80
Years
100
120
140
• What are "lifestyle"
diseases?
• Disease burden we suffer
by choice?
• The agony of reversing the
choice?
CHRISTOPHER DYE
Lifestyle diseases:
the burden of choice?
• Diseases of civilization
• Western disease paradigm
• Diseases of affluence
• Chronic diseases
• Non-communicable diseases
• Diseases of longevity
CHRISTOPHER DYE
Lifestyle diseases:
the burden of choice?
Diseases of civilization?
Western disease paradigm?
Diseases of affluence?
Deaths per million population
Where 60 million people die
double burden of disease in low-income countries
8
6
Low-middle income
High income
4
2
0
Communicable,
pregnancy,
nutrition
Noncommunicable
Injuries
Chronic diseases?
Non-communicable diseases?
 Cardiovascular disease:
heart disease, stroke
 Cancer
 Chronic respiratory
diseases
 Diabetes
us
/p
C
ar
ar
as
di
iti
ov
as c
cu
R
M
la
e
al
r
ig spi
na
r
nt ato
ca ry
nc
er
s
Pe
rin
U
ni
at
nt
en al
tio
R
es
na
pi
l
ra
to
D
ig ry
es
tiv
In
te
e
nt
io
N
M nal
eu
at
ro
ps ern
al
yc
hi
at
N
ut ric
rit
io
na
l
In
fe
ct
io
Deaths ('000s in 2001)
Top 12 causes of death: Africa/S Asia
10 000
8 000
4 000
going down slowly
6 000
going up
2 000
0
ar
di
M
ov
al
ig
as
na
cu
nt
l
ca ar
nc
R
es ers
N
eu
pi
ro
r
ps ato
ry
yc
hi
at
ric
D
ig
es
U
ni
nt tive
en
tio
R
na
es
pi
l
ra
to
ry
D
i
ab
G
en
e
ito tes
ur
in
In
ar
I
nt
fe
ct
en y
N
tio
ut iou
s/
rit
na
p
io
na ara l
si
l/e
nd tic
oc
rin
e
C
Deaths ('000s in 2001)
Top 12 causes of death: W Europe/N America
3 000
2 000
1 000
0
Diseases of longevity?
Inexorable growth in life expectancy?
100
90
80
women in leading countries
Life expectancy
Maxima estimated in
year given
source: Oeppen 2002
70
Growth: 1 extra year in 4
60
50
40
1820 1845 1870 1895 1920 1945 1970 1995 2020 2045 2070
Most years of life lost to to cancer, heart
disease, stroke are in people 45+
Total years healthy life lost
12000
10000
Cardiovascular
disease
Cancers
8000
6000
4000
2000
0
0-4
5-14
15-29
30-44
45-59
60-69
Age class (years)
70-79
80+
Obesity steeply rising among children
in USA since 1980 (CDC data)
20
18
1963-65
Percentage overweight
1971-74
16
14
12
1976-80
1988-94
1999-00
2001-02
2003-04
10
8
6
4
2
0
2-5
6-11
Age class (years)
12-19
Chronic, non-communicable
diseases in long-lived populations
Why
do we age and
die?
Life begins at 40?
Conceptions per 1000 women
Conception in women, England & Wales, 2005
140
120
100
Menopause
Median age
age 50
menopause
80
≈ 50 years
60
40
20
0
Under
16
Under
18
Under
20
20–24
25–29
30–34
35–39
40 and
over
Why we age and die
Kirkwood's "disposable soma"
Evolution acts through reproduction
Survival depends on maintenance, which
is costly after reproduction
A lifelong accumulation of faults…
Zen 禅 and the art of metabolic maintenance?
Survival of hunter-gatherers and Japanese
Percent surviving
100
80
60
40
20
0
0
20
40
60
Age (years)
80
100
Fixing the faults?
"in the end costs exceed benefits"
"…as each lifelimiting process is
countered, some
other process will
become limiting"
Doug Wallace
U California
What
causes of disease
can be modified?
Al
co
ho
l
Ch
ol
es
te
Bl
ro
oo
l
d
pr
es
su
re
O
ve
rw
ei
gh
t
Sm
Ph
ok
in
ys
g
ic
al
in
ac
Lo
tiv
w
ity
fru
it/
ve
g
di
et
Ai
rp
ol
lu
tio
n
Attributable fraction (%)
60
Ischemic heart disease: main risk factors
84% explained in high-income countries
40
20
0
-20
fr
an
ui
di
tio
l
n
oh
o
ol
lu
ity
et
t
gh
tiv
A
lc
rp
ai
in
ac
eg
t/v
ei
g
in
ok
rw
ve
al
ic
ys
w
rb
U
Ph
Lo
O
Sm
ol
re
st
er
su
es
le
pr
ho
C
od
lo
B
Attributable fraction (%)
Stroke: main risk factors
68% explained in high-income countries
60
40
20
0
-20
Trans fats 50 years of research to
get the label on the tin
Trans fat increased risk of heart disease in
20,000 women followed for 20 years
Trans fat
Polyunstaturated
fat
1766 instances
of heart attack
-0.4
-0.2
lower risk
0
I
0.2
0.4
higher risk
0.6
0.8
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
Risk of dying at age 35-69 yrs
60
England & Wales
Poland
50
40
30
Other
causes
20
Smoking
10
0
high
middle
low
social class
high
middle
education
low
Source: P
Jha Lancet
2006
"I have taken more out of alcohol
than alcohol has taken out of me"
…only two
before
breakfast
1
1/2 to 2 drinks
per day
0.8
- diet
0.6
- smoking
0.4
- activity
- weight
0.2
Alcohol (grams per day)
30
+
15
.0
-2
9.
9
5.
014
.9
0.
14.
9
0
0
Relative risk heart attack
(MI)
Alcohol lowers risk of coronary heart
disease in men with healthy lifestyles
Source:
Arch Intern
Med v166,
p2145, 2006
CVD: can all major risks can be reduced on a
large scale?
What
causes of disease
cannot be
modified?
Ph
ity
x
se
n
et
tio
tiv
e
af
in
ac
ns
U
ol
lu
l
t
gh
di
ei
eg
t/v
rp
al
ic
ys
ui
rw
ve
ai
fr
an
w
rb
U
Lo
O
oh
o
g
in
ok
A
lc
Sm
Attributable fraction (%)
All cancers: risk factors
37% explained in high income countries
60
Lung cancer: smoking 86%
40
20
0
-20
Cancer: a glimpse of immortality
Immortal germ cells
Cancer cells
Mortal somatic cells
Cancer
when
somatic
cells
revert
by
accident
to germlike
cells
"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
US Cancer Incidence Trends (1975-2003) for Top 10 sites
1975
Men
1975-92 increase
1992-95 decrease
1995-03 stable
Women
1975-79 stable
1979-03 increase
2003
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
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 air
Britons 2nd most obese in Europe
% population obese (BMI 30+)
Percent population with Body Mass Index 30+
EU countries
25
UK population ranked #2
20
15
10
5
0
Obesity in England
highest 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.
2.
3.
4.
5.
6.
7.
8.
9.
Not enough sleep (obesity <=> 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)
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
"90m children
stunted…serious
intergenerational
effects" James
Commission 2000
"…poverty
passes from one
generation to
another, as if the
offspring sucks
it from the
mother's breast"
Uganda
Status syndrome
Low social status linked to high mortality
• Shishehbor (JAMA 2006)
• 30,000 patients with heart
disease in Ohio, USA, 19902002
• 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 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"