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SCIENTIFIC DISCOVERY AND THE FUTURE OF MEDICINE
From Lifespan to Healthspan
At the turn of the 20th century, life expectancy at birth
in most of today’s developed nations ranged between
45 and 50 years, with women routinely outliving men.
About 22% of all individuals born in 1900 in the United
States died before reaching the age of 10 years, mostly
from infectious diseases.
1
Among those who survived
into older ages in 1900, the common diseases of aging
known today were present but less common.
When public health emerged in the late 19th cen-
tury, including developments such as sanitation and
clean water,early mortality swiftly declined. A rapid shift
in the distribution of death from younger to older people
occurred during the first half of the 20th century, and
since then declining death rates at middle and older
ages have led to survival into increasingly older ages.
As a result, about 96% of infants born in developed na-
tions today will live to age 50 years or older, more than
84% will survive to age 65 years or older, and 75% to
77% of all deaths will predictably occur between age 65
and 95 years.
2
With declining early-age mortality and a shift in
the age distribution of death, the population of the
United States, and much of humanity in general,
achieved exactly what was desired: the first longevity
revolution. The 30-year increase in life expectancy at
birth in the past 100 years is one of humanity’s great-
est achievements.
Lifespan Limits and Decelerating Improvements
in Life Expectancy
Over the past century, the relatively easy gains in life ex-
pectancy have been achieved by reducing mortality of
younger people; more recently, scientists have focused
on how much higher life expectancy can increase and
what the maximum lifespan is for humans. The former
is a population-based metric that involves national vital
statistics for groups of people; the latter is the world rec-
ord for longevity held by 1 person.
Regarding maximum lifespan, only a small propor-
tion of all humans are capable of living to 115 years of age,
with a small number of statistical outliers capable of ap-
proaching the world record of 122 years.
3
Some ex-
perts suggest that if death rates plateau at older ages,
lifespans may continue to increase. This latter view has
been challenged because an unrealistically high num-
ber of people (estimated at 262 200) would have to
survive to age 105 years for just 1 person to exceed the
world record for longevity by 1 yearto 123 years.
4
As such,
the probability of any substantial increase in maximum
lifespan in this century is remote.
Regarding life expectancy, one view developed in
1990 suggested that the increase in life expectancy would
soon decelerate because the easy gains had already been
achieved.
5
Any substantive future increases require im-
provements in mortality at older ages, although compo-
nents of the human body (eg, brain, heart, knees) are not
designed for long-term use. Others suggested that
historical trends in the increase in life expectancy will
continue indefinitely into the future due to yet-to-be-
developed medical advances and improved lifestyles.
Not one of the anticipated high-life-expectancy sce-
narios is remotely plausible today. In fact, a new trend
in the opposite direction has emerged in much of the de-
veloped world, indicating that death rates for many ma-
jor causes of death have either leveled off,experienced
declining improvement, or increased since 2008.
Biological Aging and Diminishing Returns
on Life Expectancy
Reductions in childhood diseases can occur only once
for a population; once such gains are achieved, the only
outlets for further gains in life expectancy must come
from extending the lives of older people. Given that
multiple fatal conditions accrue in older people because
of biological aging (eg, a fundamental and inevitable
risk that occurs independent of conventional behav-
ioral risk factors for diseases), once survival past age
65 years becomes common in a country, life expec-
tancy gains will decelerate, even with medical advances
and improved lifestyles. Because the
point of diminishing returns on life
expectancy (approximately 85 years for
men and women combined) and the
longevity limit (which has never been
exceeded) for the species has been
approached in many parts of the world,
there is good reason to conclude that the goal of life
extension has largely been achieved.
There is a dilemma. Modern medicine continues its
relentless pursuit of life extension without considering
either the consequences of success or the best way to
pursue it. The current focus of most of modern medi-
cine is on chronic fatal age-related diseases, in much the
same way infectious diseases were confronted more
than a century ago (ie, one at a time as if independent
of each other). Even though there havebeen some suc-
cesses, further life extension in an aging world will ex-
pose the saved population to an elevated risk for all other
aging-related diseases.
The principal outcome and most
important metric of success should be
the extension of healthspan.
VIEWPOINT
S. Jay Olshansky,
PhD
Division of
Epidemiology and
Biostatistics,
University of Illinois
at Chicago School of
Public Health,
Chicago.
Viewpoint
Corresponding
Author: S. Jay
Olshansky, PhD,
Division of
Epidemiology and
Biostatistics,
University of Illinois
at Chicago School of
Public Health, 1603
W Taylor St, Room
885, Chicago, IL
60612 (sjayo@uic
.edu).
Opinion
jama.com (Reprinted) JAMA Published online September 17,2018 E1
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The longer people live, the more important aging biology be-
comes as a primary risk factor in determining both length and qual-
ity of life. In long-lived populations, a substantialpar t of life,and cer-
tainly most deaths, now occur in a period in the lifespan when the
risk for frailty and disability increases exponentially.
6
In this period,
which could be called the red zone, it becomes increasingly more dif-
ficult to intervene using conventional disease-oriented ap-
proaches; the further into this period that humans venture, the more
resistant diseases become (Figure).
Because the biological processes of aging force human bodies
to become ever more susceptible to fatal and disabling conditions,
unwanted health conditions emerge in the red zone not so much be-
cause of how life has been lived (although harmful lifestyles can ac-
celerate their emergence and progression) but because of how long
life has already been lived. Time becomes the greatest challenge.
With death inevitable, the modern attempt to counteract
aging-related diseases reveals a phenomenon known as competing
risks. When the risk of death from a disease decreases, the risk
of death from other diseases increases or becomes more ap-
parent. With advancing age, the period between the emergence
of competing diseases shortens. The hazard in old age is not
so much that one disease displaces another but that the new dis-
eases are often much more debilitating. For example, finding a cure
for cancer may cause an unintended increase in the prevalence of
Alzheimer disease.
The inescapable conclusion from these observations is that life
extension should no longer be the primary goal of medicine when
applied to people older than 65 years of age. The principal out-
come and most important metric of success should be the exten-
sion of healthspan.
The First Health Revolution
The conventional approaches used to counteract the diseases of
older age have been to improve behavioral risk factors, find ways
to detect them earlier, and use medical technology to extend sur-
vival for those who already have diseases. The more important goal
of public health, medicine, biotechnology, and the health sciences
should now shift toward delaying and compressing the period of the
lifespan when frailty and disability increase substantially. Referred
to as the first health revolution,
7
this new approach for public health
(which is to target aging) is seen as a highly effective method of pri-
mary prevention.
A consortium of scientists as well as public health experts
and organizations has formed with the purpose of developing this
new approach to extend healthspan, address the diseases of ag-
ing, and help to ameliorate the economic challenges of an antici-
pated rising prevalence of late-onset diseases. This effort is called
the Longevity Dividend Initiative
8
or geroscience.
9
Clinical trials de-
signed to target aging have been approved by the US Foodand Drug
Administration, with the first trial set to begin in 2019.Large invest-
ments in aging biology have already begun through Google Calico
and Human Longevity Inc. The National Institute on Aging has es-
tablished the Interventions TestingProgram to rigorously and quickly
test prospective aging interventions for free. The National Insti-
tutes of Health has reduced the barriers between its disease-
oriented research silos, and the American Federation for Aging Re-
search is spearheading a global effort to secure funds to launch the
Longevity Dividend Initiative in 2019.
10
Conclusion
The time has come to recognize the achievement of life extension.
Efforts should be focused on achieving the goals of extending and
improving the healthspan.
ARTICLE INFORMATION
Published Online: September 17,2018.
doi:10.1001/jama.2018.12621
Conflict of Interest Disclosures: The author has
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest. Dr
Olshansky reported being cofounder and chief
scientist at Lapetus Solutions Inc. Elements of the
Longevity Dividend Initiative were funded by the
MacArthur Foundation Research Network on an
Aging Society and The Glenn Award from the Glenn
Foundation for Medical Research. No other
disclosures were reported.
REFERENCES
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Social Security Area 1900-2100. Actuarial Study
No. 120. https://www.ssa.gov/oact/NOTES/as120
/LifeTables_Tbl_6_1900.html. Accessed
August 30, 2018.
2. Human Mortality Database. https://www
.mortality.org/. Accessed July 22, 2018.
3. Dong X, Milholland B, Vijg J. Evidence for a limit
to human lifespan. Nature. 2016;538(7624):257-259.
doi:10.1038/nature19793
4. Olshansky SJ, Carnes BA. Mortality plateaus
and unlimited lifespans: let’s get real. Science.
http://science.sciencemag.org/content/360/6396
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5. Olshansky SJ, Carnes BA, Cassel C. In search of
Methuselah: estimating the upper limits to human
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doi:10.1126/science.2237414
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7. Olshansky SJ, Carnes BA. Primary prevention
with a capital P. Perspect Biol Med. 2017;60(4):478-
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8. Olshansky SJ, Martin G, Kirkland J, eds. Aging:
The Longevity Dividend. Cold Spring Harbor,NY:
Cold Spring Harbor Laboratory Press; 2015.
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Figure. Age Distribution of Life TableDeaths for Women
in the United States, per 100 000 People, 1900 and 2016
4500
4000
3000
3500
2500
2000
1500
1000
500
0
No. of Deaths per 100
000
Age, y
1111 611 16 10610121 26 31 36 41 46 51 56 61 66 71 76 81 86 91 96
2016
1900
The red zone represents a period in life when the risk of frailty and disability
begins to increase rapidly.The goal of aging science is to delay and compress
the red zone, which may extend healthy life. Sources: 1900 data from Bell and
Miller
1
; 2016 data from Human Mortality Database.
2
Opinion Viewpoint
E2 JAMA Published online September 17, 2018 (Reprinted) jama.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by MAURIZIO BASSI on 09/24/2018