Post on 25-May-2020
Professor Sarah Harper CBE Clore Professor of Gerontology
University of Oxford
October 22, 2019
The Science of Longevity, Life
Expectancy and Healthy Life
Expectancy
Worlds 1st Super- centenarian
FOUGHT WITH NAPOLEON….
Geert Adriaans Boomgaard
21 September 1788 Groningen, Netherlands
3 February 1899
110 years 135 days
Record male life until 1966
Jeanne Calment of France, who died in 1997 aged 122 years, 164 days, had the longest human lifespan documented
The oldest verified man is Jiroemon Kimura of Japan, who died in 2013 aged 116 years and 54 days
Multi-disciplinary Questions
We now understand for example
• that cellular processes are affected by behaviour and
environment, and that external factors may influence health
and ageing even at the level of genetic structures
• that society frames these processes and even global political
and economic structures have an influence
Resilience-enhancing factors such as exercise, social networks and economic security, which can protect against damage
Cell to Society: both biological and social factors are implicated in damage and repair, and interact closely
Stressorssuch as retirement, bereavement or disease, which manifest themselves during major life-course events and transitions
• To grow old in a society or world that is in itself ageing is different
from growing old in a predominantly young population. In
particular, resources start to shift as both politically and
economically older adults start to dominate societies’ agendas.
• For example, biological and cellular research into ageing has
increased considerably over past decades. Associated with
increases in life expectancies these trends, older populations have
attracted political, policy, scientific and societal interest leading to
greater funding and promotion of age-related research in all
fields.
1. Will increases in life expectancy continue?
How long will our children and
grandchildren live for?
2. Will advances in life expectancy be matched by advances in healthy life expectancy?
• Will increases in both life expectancy and in life extension or longevity continue?
– will there be an increase in average years lived by humans and also maximum years attained by a human being?
Life expectancy, selected OECD countries, men and women, birth
Source: OECD
72
74
76
78
80
82
84
86
88
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Re
mai
nin
g ye
ars
of
life
Birth
Spain women
Japan women
FrancewomenUK women
USA women
Spain men
Japan men
Life expectancy, selected OECD countries, men and women, age 60
Source: WHO
15
16
17
18
19
20
21
22
23
24
25
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Re
mai
nin
g ye
ars
of
life
Spain women
Japan women
FrancewomenUK women
USA women
Spain men
Japan men
France men
UK men
Life expectancy, selected OECD countries, men and women, age 80
Source: OECD
6
7
8
9
10
11
12
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Re
mai
nin
g ye
ars
of
life
Age 80
Spain women
Japan women
France women
UK women
USA women
Spain men
Japan men
France men
UK men
USA men
Female life expectancy at birth in 2030
Kontis et al 2017 THE LANCET 6736(16)32381-9
Posterior distribution of life expectancy and its median value. Red dots show the posterior medians.
Oldest age at which at least 50% of a birth cohort is still alive (Birth Cohorts 2000-2007)
104
101
104
102
104
107
103
104
96
98
100
102
104
106
108
2000 2001 2002 2003 2004 2005 2006 2007
Canada
DenmarkFrance
GermanyItaly
Japan
UK
Source: Human Mortality Data Base, Christiansen et al Lancet 2009
Centenarians
Leeson, G. (2014) Future prospects for longevity. Post Reproductive Health, 20 (1), 17-21
Source: Oxford Institute of Population Ageing Human Mortality Data Base
2010 2020 2030 2040 2050 2060 2070 2080
CentenariansProjected number of centenarians in the USA
6m
5m
4m
3m
2m
1m
>1m
Will increases in life expectancy be accompanied by increases in life extension or are we seeing a compression of longevity after 100?
– will the predicted increases in centenarians over the coming century be accompanied by increases in super-centenarians?
111 year old Great,great,great,grandmother
0
1000
2000
3000
4000
5000
0 10 20 30 40 50 60 70 80 90 100 110 120
Age
d(x
) fu
ncti
on
, li
fe t
ab
le
1950-1954
1960-1964
1970-1974
1980-1984
1990-1994
2000-2004
Change in the distribution of ages at death for women in Japan from 1950-54 to 2000-2004
Cheung and Robine, 2007
0
1000
2000
3000
4000
5000
0 10 20 30 40 50 60 70 80 90 100 110 120
Age
d(x
) fu
ncti
on
, li
fe t
ab
le
1950-1954
1960-1964
1970-1974
1980-1984
1990-1994
2000-2004
0
1000
2000
3000
4000
5000
0 10 20 30 40 50 60 70 80 90 100 110 120
Age
d(x
) fu
ncti
on
, li
fe t
ab
le
1950-1954
1960-1964
1970-1974
1980-1984
1990-1994
2000-2004
Change in the distribution of ages at death for women in Japan from 1950-54 to 2000-2004
Cheung and Robine, 2007
In our genes? Do some of us simply age less fast than others…..?
“….longevity case participants were healthier than controls despite the fact they were on average 10.8 years older. They possessed significantly better biological and physiological risk factor profiles, less age-related disease, and better physical and cognitive function”
Concluding with
“the concept of a “healthy aging” phenotype, whereby certain individuals are somehow able to delay or avoid major clinical disease and disability until late in life”
Robine et al 2003 The emergence of extremely old people: the case of Japan
Experimental Gerontology 38 735–739
In our Genes?
In our Genes?
“Supercentenarians displayed an exceptionally healthy aging phenotype where clinically apparent major chronic diseases and disabilities were markedly delayed, often beyond age 100. They had little clinical history of cardiovascular disease and reported no history of cancer or diabetes”.
Wilcox et al 2008 J Gerontol A Biol Sci Med Sci (2008) 63 (11): 1201-1208
“Our long-lived cases also had metabolic profiles that suggested higher insulin sensitivity at younger ages, namely lower waist:hip ratio, lower glucose levels, lower insulin.”Morris et al 2015 J Gerontol A Biol Sci Med Sci (2015) 70 (2): 133-142
Nature Debate on Longevity
X. Dong, B. Milholland & J. Vijg Nature 538, 257–259 (2016)
“Our results strongly suggest that the maximum lifespan of humans is fixed (115) and subject to natural constraints”
“….what appears to be a ‘natural limit’ is an inadvertent by-product of fixed genetic programs for early life events such as development, growth and reproduction. Limits to the duration of life could well be determined by a set of species- specific, longevity-assurance systems encoded in the genome that counteract these inadvertent by-products, which are likely to include inherent
Imperfections in transferring genetic information into cellular function”.
REPOST“Current understanding of the biology of ageing points firmly away from any idea that the end of life is itself genetically programmed….”
Will life expectancy increase
in line with life extension?
- will we all enjoy the benefits of
longevity or will it be for a few?
Source: Sample copy Viacheslav Iakobchuk
Declining US Life Expectancy: Harper, S. Kaufman, J. Cooper, Richard S
Epidemiology: November 2017 - Volume 28 -Issue 6 - p e54–e56
Have mortality improvements stalled
in England?
Editorial BMJ May 2017:357
Inequality in Mortality
Harper, S. Howse, K. Baxter, S.UK data set: 2.5 millionOccupational Pension Records
Proportion of 65 year old men expected to survive to each older age
Source: Oxford Institute of Population Ageing
100
75
50
25
0
65 75 85 95Age
% probability of reaching age x
Unhealthy lifestyle, ill health retiree, poor
Healthy lifestyle, normal health retiree, rich
‘Average’ individual
Life Expectancy and Healthy Life Expectancy
Title of presentationSource: Future of an Ageing Population, Foresight, 2016
RISKS
1. Will increases in life expectancy continue?
2. Will advances in life expectancy be matched by advances in healthy life expectancy?
Life expectancy (LE) and healthy life years (HLY), selected countries, women at age 60
Source: WHO
15
17
19
21
23
25
27
29
31
2000 2005 2010 2015
Re
mai
nin
g ye
ars
of
life
Spain LE
France LE
Japan LE
UK LE
USA LE
Spain HLE
France HLE
Japan HLE
UK HLE
USA HLE
Life expectancy (LE) and healthy life years (HLY), selected EU countries, women, age 80
1
2
3
4
5
6
7
8
9
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Re
mai
nin
g ye
ars
of
life
France LE
Spain LE
UK LE
France HLY
Spain HLY
UK HLY
Source: http://www.eurohex.eu/
A Potential Decline in Life Expectancy in the United States in the 21st Century, Olshansky S J et al 2005 N Engl J Med 2005; 352:1138-1145
“There are other realistic threats to increases in life expectancy…. death from infectious diseases …..fuelled mostly by the AIDS epidemic ….”
“We anticipate that as a result of the substantial rise in the prevalence of obesity and its life-shortening complications such as diabetes, life expectancy at birth and at older ages could level off or even decline within the first half of this century”.
Higher BMI is associated with risk factors for vascular disease
BMI 15-50kg/m2
Excluding first 5 years of follow-up
Lopez-Jimenez F. The Lancet. 2009.
0
10
20
30
40
50
60
70
80
90
100A
ge-a
dju
sted
rel
ativ
e ri
sk o
f d
iab
etes
BMI category (kg/m2)Colditz et al. (1995) Ann Intern Med 122(7): 481-6
Higher BMI is associated with an increased risk of diabetes
Higher BMI is associated with reduced life expectancy
Lopez-Jimenez F. The Lancet. 2009.
Oxford Institute of Population Ageing
Increase in
Disabled Years
Age 55 Reduced
LE
Increased
DY
Obesity 1.4 5.9
Smoking 4 3.8
Alcohol 3 3.1Klijs et al., 2011Obesity, smoking, alcohol consumption
and years lived with disability, BMC Public Health 11:378
RISKS
1. Will increases in life expectancy continue?
2. Will advances in life expectancy be matched by advances in healthy life expectancy?
3. Even with advances in healthy life expectancy, will increases in the numbers of older adults increase morbidity within the population?
Two decade comparison of incidence rates for dementia in 65+ population –big improvement in ‘brain health’
Cognitive Function and Ageing Study – Nature Communications 2016 – FE Matthews et al.
Estimated 183,000 cases in UK in 1991. Using 1991 IRs, projected estimate for 2015 would be 251,000 i.e. 37% increase as a result of population change (growth + ageing)
Based on 2011 IRs, estimated 210,000 cases in UK in 2015, i.e. much smaller than CFAS I projection. Age-standardised incidence in 65+ fell by 20% over two decades. But still a 15% increase in absolute numbers (new cases per year)
Dementia prevalence declined significantly, from 11.6%in 2000 to 8.8% in 2012. Influence of one years extra schooling.
21,000 US adults 65 years or older from the nationally representative Health and Retirement Study.
Cognitive reserve hypothesis— clinical manifestation of dementia is delayed in people with higher education, a steeper decline occurs at a certain threshold.
Langa et al, 2016 A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012 JAMA Intern Med..2016.6807
Estimated numbers of people with dementia by age: big increase in numbers even if incidence continues to decline
I
Assumes 2.7% annual decline in incidence
Ahmadi-Abhari et al 2017
25% increase in numbers of older people with disability (unable to carry out 1 or more ADL) if age-specific risk of serious disability declines
Model (IMPACT-BAM) assumes continuing reductions in incidence of dementia and CVD as well as continuing mortality reductions.
Guzman-Castillo et al 2017
Crude incidence of heart failure would be reduced by 18% if whole population had incidence of least deprived quintile
Conrad et al Lancet 2018
Determinants of the shape of mortality and morbidity in 21st Century
• Healthy Living
• Disease Prevention and Cure
• Regenerative medicine
• Age-Retardation.
Key Question
How much life expectancy can we expect to gain without the intensive application of scientific medicine?
Estimate the impact on life expectancy of delaying the onset of what we know to be age-related diseases rather than eliminating them altogether.
16%
18%
13%
4%
15%
28%
33%
28%
13%
31%
0%
5%
10%
15%
20%
25%
30%
35%
Heart disease Stroke Cardiovasular disease Cancer Premature death
Percentage reduced risk in developing illness
2 and a half portions 10 portions
Source: International Journal of Epidemiology
Determinants of the shape of mortality and morbidity in 21st Century
• Healthy Living
• Disease Prevention and Cure
• Regenerative medicine
• Age-Retardation.
Key Question
How much life expectancy can we expect to gain with the intensive application of scientific medicine?
Pushing back death into later and later ages
Projected increase in deaths for England & Wales 2014-2040. Bone et al 2017
https://www.gov.uk/government/.../future-of-an-ageing-population
https://www.gov.uk › Industrial Strategy: the Grand Challenges
https://www.gov.uk/government/publications/harnessing-technology-to-meet-increasing-case-needs
https://www.ageing.ox.ac.uk/news/industrial-challenge-healthy-ageing