The Future of Life Expectancy by James W.

The Future of Life Expectancy by James W.

The Future of Life Expectancy by James W. Vaupel IAA Mortality Working Group, St. Petersburg, 27 May 2016 View 1: Fixed frontier The fixed frontier of survival in evolutionary theories of aging Peter Medawar Mutation accumulation George Williams Antagonistic pleiotropy William Hamilton Thomas Kirkwood Demographic

mathematics Disposable soma Annette Baudisch Inevitable senescence? William Hamilton (1966, 1996) I show that no life schedule, even under the most benign ecology imaginable, could escape my spectrum of forces of selection. William Hamilton (1966, 1996) I show that no life schedule, even under the most benign ecology imaginable, could escape my spectrum of forces of selection. after a few hundred years of draconian eugenic

measuresthe human lifespan might be stretched out just a littlesay [to] 75 instead of 70. William Hamilton (1966, 1996) I show that no life schedule, even under the most benign ecology imaginable, could escape my spectrum of forces of selection. after a few hundred years of draconian eugenic measuresthe human lifespan might be stretched out just a littlesay [to] 75 instead of 70. [Research on] extension of active life seems to me comparable with the alchemists search.[and] detracts both from unavoidable truth and from realistic social programs. View 2: Secret of longevity Luigi Cornaro

year age possible claimed age 1540 56 56 1557 80 73 1565 95

81 Determinants of Longevity Average lifespan in a population Biomedical knowledge, health care system, standard of living, education, healthy behavior, environment Variation in lifespans among individuals Determinants of individual longevity Determinants of individual longevity Source: Determinants of individual longevity

Determinants of individual longevity Listen to your mother View 3: Advancing frontier Hans Lundstrm The frontier of survival 0.6 Mortality at ages 85, 90 and 95 for Swedish females 0.5 0.4

0.3 Risk of Death Age 95 0.2 Age 90 0.1 0 1900 Age 85 1920 1940

1960 1980 2000 Year Discovery of the Advancing Frontier of Survival: The Decline in Octogenarian Mortality Women, Ages 80-89 Men, Ages 80-89 Source: Calculations by Roland Rau (unpublished) based on Human Mortality Data Base The frontier of survival The explosion of centenarians Number of females aged 100+ or 105+

1860 5 2010 1369 Year Advancing frontier 1973 12 600 1000 1400 1800 2200

Swedes 100+ Japanese 105+ 2010 2352 0 200 Number of females aged 100+ or 105+ The explosion of centenarians 1860 1900 1940 Year 1980

2020 What do we know about the physiology of human longevity? MAJOR DISCOVERY: The frontier of survival is advancing: old-age mortality is not intractable SUPPLEMENTAL DISCOVERIES: 1. The frontier of survival is advancing because senescence is being delayed, not decelerated. The Postponement of Senescence: Evidence from Sweden 1 Swedish Females 1950

Risk of Death Age 30-90 0.1 1980 68=57 2010 0.01 0.001 57 63 68 0.0001 30 40

50 60 70 80 90 Age Data from Human Mortality Database. Also see ChristensenVaupel ,Lancet 2010, 2013. Current age and age of equivalent mortality 50 years ago. Equivalent Age 50 Years Ago Age

Female Male France Sweden England Japan & Wales France Sweden England & Wales Japan 50 42 40 42 23

44 43 43 39 60 49 52 52 43 51

53 51 50 70 59 62 62 53 59 62 59

57 80 71 72 73 67 71 73 72 70

90 83 85 83 79 84 87 82 81 What do we know about the physiology of human longevity? MAJOR DISCOVERY:

The frontier of survival is advancing: old-age mortality is not intractable SUPPLEMENTAL DISCOVERIES: 1. The frontier of survival is advancing because senescence is being delayed, not decelerated. 2. Life expectancy is rising linearly, with no sign of a looming limit. The frontier of survival 95 Australia Life expectancy in years 90 The life expectancy revolution

Netherlands Switzerland 85 80 75 70 Sweden Iceland Japan New Zealand Norway Germany 65 60 55 50 45

Year 1840 1860 1880 1900 1920 1940 1960 1980 2000 2020 The Revolution in Record Life Expectancy Oeppen & Vaupel Science 2002; extended Data Source: Calculations based on Human Mortality Database from Roland Rau and James Vaupel (unpublished) 20/33 Life expectancy: might rise more slowly than in the past, perhaps approaching a limit that is not much greater than the current best-practice level, with some chance that life expectancy might fall. in the countries doing best, might continue to rise at the historical pace of almost 3 months/year for the next several decades and perhaps longer. might rise substantially faster than this, because of major biomedical breakthroughs.

A.Best-practice national life expectancy (for women) has been rising linearly for the past 175 years at a steady pace of about 2.5 years per decade. The record is now above 87. Over the next 50 years do you think that this record will increase: 1. Even faster--by more than 3 years per decade, reaching 102 or more; 2. At about the same pace--by 2-3 years per decade, approaching 100 or so; 3. At a slower and slower pacedeclining from 2.5 years per decade to roughly 1 year per decade, reaching perhaps 95 or so; 4. At a much slower pace, reaching a plateau, a life-expectancy limit, not much higher than the current record of 87perhaps 90 or so; A.Best-practice national life expectancy (for women) has been rising linearly for the past 175 years at a steady pace of about 2.5 years per decade. The record is now above 87. Over the next 50 years do you think that this record will increase: 1. Even faster--by more than 3 years per decade, reaching 102 or

more; 6% 2. About the same pace, by 2-3 years per decade, approaching 100 or so; 9% 3. At a slower and slower pacedeclining from 2.5 years per decade to roughly 1 year per decade, reaching perhaps 95 or so; 22% 4. At a much slower pace, reaching a plateau, a life-expectancy limit, not much higher than the current record of 87perhaps 90 or so; 59% B. What do you think the probability is that record life expectancy will increase at about the same pace as in

the past or somewhat fasterby at least 2 years per decade on average over the next 50 years, reaching a level of 97 or more? 1. Likely: at least 50% chance. 2. Possible but not likely: more than 25% but less than 50% chance. 3. Unlikely: more than 5% but less than 25% chance. 4. Very unlikely: less than 5% chance. B. What do you think the probability is that record life expectancy will increase at about the same pace as in the past or somewhat fasterby at least 2 years per decade on average over the next 50 years, reaching a level of 97 or more? 1. Likely: at least 50% chance. 27% 2. Possible but not likely: more than 25% but less than 50% chance. 56%

3. Unlikely: more than 5% but less than 25% chance. 16% 4. Very unlikely: less than 5% chance. C. What do you think the probability is that record life expectancy will increase slowly or maybe even decline over the next 50 years, reaching a level less than 90. 1. Likely: at least 50% chance. 2. Possible but not likely: more than 25% but less than 50% chance. 3. Unlikely: more than 5% but less than 25% chance. 4. Very unlikely: less than 5% chance. C. What do you think the probability is that record life expectancy will increase slowly or maybe even decline over the next 50 years, reaching a level less than 90. 1. Likely: at least 50% chance. 4% 2. Possible but not likely: more than 25% but less than

50% chance. 18% 3. Unlikely: more than 5% but less than 25% chance. 39% 4. Very unlikely: less than 5% chance. 45% The Sorry Saga of Looming Limits to Life Expectancy Oeppen and Vaupel Science 2002 95 UN World Bank 90 Olshansky et al. UN Fries, Olshansky et al.,

Coale, Coale & Guo 85 Life-expectancy in years World Bank, UN Bourgeois-Pichat, UN Siegel Bourgeois-Pichat UN, Frejka 80 75 Dublin Dublin & Lotka 70 65

Dublin 60 55 50 45 1840 1860 1880 1900 1920 1940 1960

Year 1980 2000 2020 2040 The Future will be different from the past Since 1840, future progress in extending life expectancy has been different from past progress. The country with the longest life expectancy has shifted from Sweden to Japan The causes of death against which progress has

been made have shifted from infectious diseases to chronic diseases The ages at which mortality has been reduced have shifted from childhood to old age Age-Specific Contributions to the Increase of Record Life Expectancy among Women 1850 to 2009 in % Age group 18501901 19011925 19251950 19501975

19751990 19902009 0 14 32 15 21 10 4 1-14

55 8 16 12 4 2 15-49 25 38 39 20

7 4 50-64 3 13 19 17 20 11 65-79

2 8 11 24 41 37 80+ 0 1 0 6

17 41 100 100 100 100 100 100 Total Data Source: Calculations based on Human Mortality Database by Roland Rau and James Vaupel (unpublished)

The Future Will Be Different from the Past In next decade or two, progress against cancer and dementia and in developing genotype-specific therapies Then progress in regenerating and eventually rejuvenating tissues and organs Accompanied by progress in replacing deleterious genes (CRISPR) Aided by nanotechnologies (nanobots) Perhaps in a decade or two, probably later, progress in slowing the rate of aging (as opposed to further postponing aging). Postponement vs. Deceleration of Senescence: Risk of Death 1 Swedish Females Age 30-90

0.1 0.01 0.001 0.0001 30 40 50 60 Age 70 80

90 D. Consider the lifespans of the cohort of infants born in England & Wales in 2016. What is the chance the average lifespan for this cohort will exceed 100? 1. Likely: 50% or more. 2. Possible but not likely: more than 25% but less than 50%. 3. Unlikely: more than 5% but less than 25%. 4. Very unlikely: less than 5%. D. Consider the lifespans of the cohort of infants born in England & Wales in 2016. What is the chance the average lifespan for this cohort will exceed 100? 1. Likely: 50% or more. 40% 2. Possible but not likely: more than 25% but less than

50%. 46% 3. Unlikely: more than 5% but less than 25%. 14% 4. Very unlikely: less than 5%. 1% E. Consider the lifespans of the cohort of infants born in England & Wales in 2016. What is the chance the average lifespan for this cohort will exceed 120? 1. Likely: 50% or more. 2. Possible but not likely: more than 25% but less than 50%. 3. Unlikely: more than 5% but less than 25%. 4. Very unlikely: less than 5%. E.

Consider the lifespans of the cohort of infants born in England & Wales in 2016. What is the chance the average lifespan for this cohort will exceed 120? 1. Likely: 50% or more. 2% 2. Possible but not likely: more than 25% but less than 50%. 25% 3. Unlikely: more than 5% but less than 25%. 32% 4. Very unlikely: less than 5%. 40% Forecasting Cohort Life Expectancy For birth cohorts, life expectancy may increase by 4 months per year.

If so, most people born in Great Britain since 2000 will celebrate their 100th birthdays. Oldest Age at which at least 50% of a Birth Cohort is Still Alive Christensen, Doblhammer, Rau & Vaupel Lancet 2009, extended Year of Birth: 2000 2005 2010 France 102 104 105 Germany

100 101 103 Great Britain 102 103 105 Japan 105 107

108 Sweden 101 102 104 USA 101 103 105 Data are ages in years. Baseline data were obtained from the Human Mortality Database and refer to the total population of the respective countries.

The Rise in Record Life Expectancy at Age 65 Data Source: Calculations based on Human Mortality Database from Roland Rau and James Vaupel (unpublished) Consider the remaining life expectancy of people in England and Wales at age 65, currently about 20 years. How much will this value increase over the next 30 years? 1. 5 years or more. 2. More than 2 but less than 5 years. 3. More than 6 months but less than 2 years. 4. Close to zero: less than 6 months and perhaps the value might even decline. Consider the remaining life expectancy of people in England and Wales at age 65, currently about 20 years. How much will this value increase over the next 30 years? 1. 5 years or more. 50%

2. More than 2 but less than 5 years. 44% 3. More than 6 months but less than 2 years. 6% 4. Close to zero: less than 6 months and perhaps the value might even decline. French female longevity Year 2012 period Born e65 23 Ave. lifespan 88

French female longevity Year 2012 period cohort Born 1947 e65 23 27 Ave. lifespan 88 92 French female longevity Year Born 2012 period cohort 1947

cohort* e65 23 27 28 Ave. lifespan 88 92 93 *Rate of ageing slowed at a rate of 2%/year after 2030 French female longevity Year Born 2012 period cohort 1947 cohort*

2030 cohort 1965 e65 23 27 28 30 Ave. lifespan 88 92 93 95 French female longevity Year Born 2012 period cohort 1947 cohort* 2030 cohort 1965

cohort* e65 23 27 28 30 38 Ave. lifespan 88 92 93 95 103 *Rate of ageing slowed at a rate of 2%/year after 2030 French female longevity Year

2012 period cohort cohort* 2030 cohort cohort* 2060 cohort Born 1947 1965 1995 e65 23 27 28 30 38 38 Ave. lifespan

88 92 93 95 103 103 French female longevity Year Born e65 Ave. lifespan 2012 period 23 88 cohort 1947 27 92 cohort* 28 93

2030 cohort 1965 30 95 cohort* 38 103 2060 cohort 1995 38 103 cohort* 67 132 *Rate of ageing slowed at a rate of 2%/year after 2030 French female longevity Year Born e65 Ave. lifespan 2012 period

23 88 cohort 1947 27 92 cohort* 28 93 2030 cohort 1965 30 95 cohort* 38 103 Risk 2060 cohort 1995 38 103 cohort* 67 132 Big Risk *Rate of ageing slowed at a rate of 2%/year

after 2030 The Failure of Expert Imagination Mortality forecasts based on expert judgment have been less accurate than extrapolation. The Best Forecasting Strategy At present the best way to forecast life expectancy is to extrapolate long-term historical trends from countries with high life expectancy. And then to ask: why might progress be faster? Why might it be slower? Q: Will the postponement of senescence continue, leading to reductions in mortality after age 100? Q: Will the rate of ageing be slowed down, leading to even greater improvements? How important is the Human Mortality Database to your work? 1. Very important and I would strongly favor

improving it to include more up-to-date statistics, data for other populations, corrections of problematic data, etc. 2. Important but substantial improvements are not needed. 3. Of some value. 4. Of little or no value. How important is the Human Mortality Database to your work? 1. Very important and I would strongly favor improving it to include more up-to-date statistics, data for other populations, corrections of problematic data, etc. 59% 2. Important but substantial improvements are not needed. 15% 3. Of some value.

25% Research on the advancing frontier of survival MaxO MaxO Odense Odense MPIDR MPIDR Rostock Rostock Key publications James W. Vaupel and Hans Lundstrm (1994) Longer Life Expectancy? Evidence from Sweden of Reductions in Mortality Rates at Advanced Ages in David A. Wise (editor) Studies in the Economics of Aging, U. of Chicago Press, pp. 79-94. This chapter presented the twin discoveries about the advancing frontier of human survival that Vaupel made in 1992 based on Swedish data compiled for him by Hans Lundstrm at Statistics Sweden. Unfortunately the research was presented in 1992 to a group of health and labor economists who did not understand the significance of the discoveries and the research was published in 1994 in a rather obscure book

of the proceedings of the 1992 workshop. An article by Vaupel et al. in Science introduced a much wider audience to the research breakthroughs: J.W. Vaupel et al. (1998) Biodemographic Trajectories of Longevity, Science 280, pp. 855-860. . Jim Oeppen and James W. Vaupel (2002) Broken Limits to Life Expectancy, Science 296, pp. 1029-1031. Although demographers knew that life expectancy was tending to increase in most countries, it was not realized until this article was published that an astonishing regularity underlay the progress: in the populations doing best, life expectancy has increased from a bit over 45 for Swedish women in 1840 to more than 87 for Japanese women today. The rise has been linear3 months per year. James W. Vaupel (2010) Biodemography of Human Ageing, Nature 464, pp. 536-542. This comprehensive review describes Vaupels discoveries and their implications for research and for society. James W. Vaupel (2005) The Biodemography of Aging in L.J. Waite (editor) Aging, Health, and Public Policy: Demographic and Economic Perspectives, Population Council, New York, pp. 48-62 (Population and Development Review; 30, 2004, Suppl.). This is an earlier account by Vaupel of his research; the material in it is a lightly-edited transcript of impromptu remarks Vaupel made to a group of students. James R. Carey,, James W. Vaupel (1992) Slowing of Mortality Rates at Older Ages in Large Medfly Cohorts, Science 258, pp. 457-461. James W. Curtsinger,, James W. Vaupel (1992) Biodemography of Genotypes: Failure of the Limited Lifespan Paradigm in Drosophila melanogaster, Science 258, pp. 461-463.

Key publications continued James W. Vaupel, Annette Baudisch et al. (2004) The Case for Negative Senescence, Theoretical Population Biology 65, pp. 339-351. Annette Baudisch and James W. Vaupel (2012) Getting to the Root of Aging, Science 338, pp. 618-619. This short article summarizes why Hamilton was wrong: senescence is not inevitable. Owen R. Jones,, James W. Vaupel (2014) Diversity of Ageing across the Tree of Life, Nature 505, 169-173. Ralf Schaible,, James W. Vaupel (2015) Constant Mortality and Fertility over Age in Hydra, PNAS December 2015. Fernando Colchero,, James W. Vaupel (2015) Lifespan Equality and Life Expectancy in Humans and Other Primates, Science, under review. . A fuller list of Vaupels publications can be found at user.demogr.mpg.de/jwv. This website provides electronic access to most of his articles. The website also provides access to several non-technical descriptions, published in the Lancet and elsewhere, of Vaupel and his research.

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