By Themis Halka
Over the past few decades, life expectancy has drastically increased worldwide – reaching an average of 71 years old in 20191. This mortality shift has emerged from an overall improvement in living conditions: increased income, nutrition, education, and medical access.2 In a 2002 paper, life expectancies in Sweden and Japan were described as increasing three months per year since 1840, and Japanese women currently have the highest worldwide life expectancy, of 87 years.1 In 2020, the UN estimated that there were over 573,000 living centenarians.3 Nowadays, numerous countries still experience an increase in life expectancy. In others though, this trend seems to have already slowed down. Has life expectancy reached a limit?
In 1825, at the onset of demographic analyses interested in life expectancy, Benjamin Gombertz developed a model of linear association between ageing and mortality risk.4 According to him, the risk of dying increases with age, until reaching 100 – the presumed limit of a human lifespan. In the late 1990s, mathematicians used his model to re-set this limit at 120 years.3 Importantly, they also speculated that medical advances in controlling ageing and treating chronic diseases could theoretically bend the curve, which would nevertheless reach a 100% mortality risk at some point3. Whilst many demographers share this idea of a natural ceiling, others have developed another model theory, suggesting that the association between mortality risk and age is not linear, but instead reaches a plateau from a certain age. In other words, there would be no mortality-determined limit to the possible lifespan. The risk of death at any age would increase exponentially during young adulthood, but a deceleration of mortality rates from 80 years old would then smooth the curve.5
Which theory is right? The question is still debated. An important issue regarding mortality demographic studies is the unreliability of data.3 Incorrect birth reports and fraud, for example, impact the reliability of data gathered on lifespan – potentially leading to biased conclusions about reduced mortality risks at very old ages. To counter this problem, databases recording centenarians’ and supercentenarians’ ages with a careful review of their documents have been created, like the International Database of Longevity (IDL).2 Despite such sources being more reliable, there remains conflicting theories on both natural ceiling and plateau life expectancy models.
As theories about the biological limits of the human lifespan depend on mortality risks at extreme ages, Barbi et al. conducted a study on Italians aged 105 years and over between 2009 and 2015, observing a constant hazard curve (plateau).5 This supported the existence of a plateau for extreme-age mortality, in disagreement with another study from Gavrilov et al.6, which modelled the hazard rate to keep growing, even after 110 years of age. These two studies are examples of an extensive pool of demographic studies about ageing, that are unfortunately limited by the small study cohorts. They highlight the complexity of determining whether gradual and consistent ageing preludes death, or if the process of ageing could be paused at some point.
Ageing is characterised by a progressive loss of physiological integrity, which leads to impaired function and increases vulnerability to death.7 Lopez-Otin et al. attempted to identify the hallmarks of ageing to better understand and describe this natural process.7 Nine tentative hallmarks were determined: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cell exhaustion, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. This natural breakdown in the cellular machinery seems inevitable and is not expected to stop after a certain age. Would the potential lifespan of a human therefore be required to have a limit?
Another major insight provided by science, though, concerns ageing research. Up until now, an increase in life expectancy and reduced mortality rate has mainly resulted from countering the symptoms and consequences of ageing. What if new biomedical research could target the causes of ageing, and slow the process down? Could life expectancy be boosted as a result of ageing research?
Researching how ageing is controlled, and what mechanisms mediate ageing, has opened a range of new targets in efforts to slow down ageing. Novel therapies and approaches to combat ageing are being trialled, targeting certain hallmarks of ageing. Whilst highly complex, many approaches look to target key metabolic and signalling pathways to tackle some sources of damage, and slow down ageing in a certain measure.3 One such promising target is autophagy, a biological process by which cells dispose of damaged components.8 Slowed in ageing, autophagy is involved in the accumulation of damage – as such, trying to boost autophagy might decrease damage accumulation in cells. Successful studies have been carried out in worms, flies and more recently mice.8 However, there is still a long way to go before this can be applied to humans, as targeting the wrong parts of the pathway could be more harmful than beneficial. Autophagy is a complex pathway, and several companies and research groups are currently developing drugs that focus on specific aspects of the pathway to ensure interventions are targeted and safe.8
With recent advances in biotechnology and medical research, life expectancy may continue to increase. This has wide-reaching impact, as many socio-cultural practices are based on life expectancy – for instance, the question of appropriate retirement age. It seems that a lifespan limit might exist, but that it is not an unchangeable limit – focused interventions on the causes of ageing may be able to increase the average lifespan. However, it is important to also pay consideration towards how an increased human lifespan may affect long-held social customs.
References:
- Oeppen J, Vaupel JW. Demography. Broken limits to life expectancy. Science. 2002 May 10; 296(5570): 1029-31. doi: 10.1126/science.1069675
- Riley J. Rising Life Expectancy: A Global History. Cambridge Univ. Press, Cambridge. 2001. p. 243.
- Eisenstein M. Does the human lifespan have a limit? Nature. 2022 Jan;601(7893):S2-S4. doi: 10.1038/d41586-022-00070-1.
- Kirkwood TB. Deciphering death: a commentary on Gompertz (1825) ‘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’. Philos Trans R Soc Lond B Biol Sci. 2015; 370(1666): 20140379. doi:10.1098/rstb.2014.0379
- Barbi E, Lagona F, Marsili M, Vaupel JW, Wachter KW. The plateau of human mortality: Demography of longevity pioneers. Science. 2018; 360(6396): 1459-1461. doi:10.1126/science.aat3119
- Gavrilov LA, Gavrilova NS, Krutko VN. Mortality of supercentenarians: Does it grow with age? Living to 100 Monograph, T. F. Harris, Ed. (Society of Actuaries, 2017), pp. 1–24.
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6; 153(6): 1194-217. doi: 10.1016/j.cell.2013.05.039.
- Dolgin E. The biological clean-ups that could combat age-related disease. Nature. 2022 Jan; 601(7893): S15-S17. doi: 10.1038/d41586-022-00075-w
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