By Rebecca Fleeman

The world’s oldest living female, Sister André (Lucile Randon), is currently 118 years old and if she lives four more years, she will be crowned the longest living human ever. The title is currently held by Jeanne Louise Calment, who was 122 years old and passed away in 1997. The longest living male is currently Juan Vicente Pérez, who is 113 years old, and chasing after Jiroemon Kimura’s record as the longest male to live (116 years). Globally, the average life expectancy of females at birth is 75.6 and for males is 70.8; thus, the impressive feats of André and Pérez surpass the world life expectancy averages by roughly 60%! Life expectancies vary by sex, country, race, socioeconomic status, environmental factors, and more, making predicting lifespan a difficult task. The average lifespan of humans has come a long way, where until the 1900s, we have no data of a human living past the 5^th decade of life (Figure 1). So how did we get from 50 years to 70+ years, and does our future extend beyond the 118 year record?

Models, Laws, and Theories of Mortality

Way back in 1825, an actuary named Benjamin Gompertz wrote an iconic paper detailing the mathematical function for human mortality which now touts over 2,000 citations¹. He believed there was no limit to the human lifespan and wanted to increase the accuracy of lifespan predictions to improve his career outcomes with buying and selling insurance. Gompertz’s law worked well to describe natural mortality, but his function failed to consider random mortality and thus underestimated death after the age of 60-70 and overestimated death in young children. His equation was picked up by William Matthew Makeham in 1860, who added an extra component to improve the function’s ability to predict mortality at extremity ages^2,3. Together, these mathematicians produced one of the most common mortality models still used today called the Gompertz–Makeham Law of Mortality. Simply put, their function predicts the odds of death with increasing age (Figure 2).

In 1960, Stehler and Milvan surmised the mechanisms underlying the mathematical models of aging in their seminal work, Stehler-Milvan Theory of Mortality and Aging⁴. They postulate that “an organism dies when stress magnitude exceeds the organism’s maximum ability to compensate therefore” and that variability amongst all species mortality is dependent on the interaction of genetic and environmental factors that contribute to maturation⁴.

The 1960s were a big decade for the field of aging as cellular aspects of the aging process were finally being explored. Up until 1965, scientists believed that cells could replicate indefinitely. In a series of in vitro experiments, Leonard Hayflick determined that human cells can only divide 40-60 times⁵, a phenomenon now called the Hayflick Limit. His seminal findings, cited over 4,000 times, set the groundwork for the 2009 Nobel Prize winners Elizabeth Blackburn, Jack Szostak, and Carol Greider, who in 2009 discovered how chromosomes are protected by telomeres. Telomeres are regions of repetitive DNA sequences found at the end of chromosomes that safeguard our DNA from damage but become shorter as we age. The Hayflick Limit, discovery of telomere mechanisms, and the following studies that stood on the shoulders of these legendary aging researchers have uncovered the details for how long humans may live.

How Long Will We Live?

We have modern medicine to thank for making it past the 5^th decade of life. The improvement to sterile techniques, preventative medicine, and therapeutic advancements have all contributed to our longevity. However, it is notable that life expectancy has taken a downturn in recent years due to the COVID-19 pandemic increasing death tolls⁶ (Figure 3). While we are not sure what COVID-19 may do to alter longevity in the long term, there have been several recent studies aiming to understand if we can 1) increase the average lifespan of humans and 2) increase the record lifespan in the future. Pre-pandemic, there were more than 500,000 centenarians (those living to be 100+) around the world, and projected estimates showed that by 2050 we would likely have over 3.5 million centenarians⁷! Belzile et al. recently predicted that given the current centenarians rates, it is likely that within this century, someone will live to be 130 years old⁸.

Mechanistic studies for mortality probabilities are underway as well. A 2021 study in Nature Communications used previously collected Complete Blood Count (CBC) and mortality estimate data from large studies to identify the absolute limit of the human lifespan⁹. Their mathematical models predict that the human lifespan has a finite number of years at 120-150 years of life⁹, due to the body’s inevitable loss of physiological resiliency to stressors.

The CBC mechanistic study follows a 2016 Nature Letter that relied solely on mortality data, focusing on maximum reported age at death (MRAD). Their results suggested that there is only a 1 in 10,000 chance that a human could live longer than 125 years ¹⁰; however, the authors note that “limits to the duration of life could well be determined by a set of species-specific, longevity-assurance systems encoded in the genome … likely to include inherent imperfections in transferring genetic information into cellular function.” Interestingly, only about 20-30% of your age of mortality is determined by genetics¹¹. The remaining 70-80% is up to lifestyle and environmental factors¹¹, as described more below.

Increasing Your Healthspan

Potentially more difficult than predicting lifespan is predicting healthspan, or the part of a person’s life where they are generally in good health. And as the classic Bon Jovi song goes, “I ain’t gonna live forever; I just wanna live while I’m alive.” What is the point of living to be 130 years old, if the last 40 of those years are burdened with debilitating health concern? Exciting research on how we can increase our lifespan and healthspan has partially centered around learning from hubs of healthy agers across the globe dubbed the Blue Zones¹² (Figure 4).

In 2004, Dan Buettner traveled to the five Blue Zones and found nine common factors that led to these populations living longer, healthier lifestyles¹². The nine factors include:

1. Exercise daily with functional day-to day movements
2. Have a reason for living each day
3. Take time to slow down
4. Eat until 80% full to maintain weight
5. Consume plant sources of protein more than meat
6. Drink a glass of wine a day
7. Participate in a community
8. Prioritize family
9. Hang out with healthy people

MORE  details on “The Power 9” can be found here.

Excitingly, it is never too late (or too early) to pick up healthy behaviors. Whether it is eating better, exercising more, or quitting smoking, research has shown that even improving habits late in life can have an impact on longevity and disease risk^9,13. Through public health policy implementation, infrastructure improvement, as well as increased nutritional and physical activity education inside and outside of school, increases in healthspan are entirely within reach¹².

TL:DR

• The global average human lifespan is currently 75.6 (female) and 70.8 (male)
• COVID-19 decreased average lifespan, but new evidence suggests humans have the potential to live 130 years
• Blue Zones (longevity hotspots) have elucidated ways to increase healthspan and lifespan

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References

1.        XXIV. On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies. In a letter to Francis Baily, Esq. F. R. S. &c. Philos Trans R Soc Lond 115, 513–583 (1825).

2.        Makeham, W. M. On the Law of Mortality and the Construction of Annuity Tables. J Inst Actuar 8, 301–310 (1860).

3.        Richards, S. J. A handbook of parametric survival models for actuarial use. http://dx.doi.org/10.1080/03461238.2010.506688 233–257 (2012) doi:10.1080/03461238.2010.506688.

4.        STREHLER, B. L. & MILDVAN, A. S. General theory of mortality and aging. Science (1979) 132, 14–21 (1960).

5.        Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37, 614–636 (1965).

6.        Arias, E., Tejada-Vera, B., Kochanek, K. D. & Ahmad, F. B. Provisional Life Expectancy Estimates for 2021. (2022) doi:10.15620/CDC:118999.

7.        World population ages 100 and up to grow eightfold by 2050, UN projects | Pew Research Center. https://www.pewresearch.org/fact-tank/2016/04/21/worlds-centenarian-population-projected-to-grow-eightfold-by-2050/.

8.        Pyrkov, T. v. et al. Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit. Nature Communications 2021 12:1 12, 1–10 (2021).

9.        Dong, X., Milholland, B. & Vijg, J. Evidence for a limit to human lifespan. Nature 2016 538:7624 538, 257–259 (2016).

10.      Herskind, A. M. et al. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum Genet 97, 319–323 (1996).

11.      Buettner, D. & Skemp, S. Blue Zones: Lessons From the World’s Longest Lived. Am J Lifestyle Med 10, 318 (2016).

12.      del Pozo Cruz, B., Ahmadi, M., Naismith, S. L. & Stamatakis, E. Association of Daily Step Count and Intensity With Incident Dementia in 78 430 Adults Living in the UK. JAMA Neurol (2022) doi:10.1001/JAMANEUROL.2022.2672.