From Ageing to Augmented Longevity

ETHOS Issue 20, Jan 2019

Ageing and Longevity

Human beings have always tried to live longer while growing older. Although ageing is still often associated with pessimism and decline, lifespans and healthspans have been significantly and steadily increasing over the past two centuries. Furthermore, there are signs that the trend towards longer and healthier lives will continue, with increased investment in anti-ageing solutions and rapid advancements in biotechnology. The successful augmentation of our bodies at a biochemical, cellular and even genetic level, to delay (or even defeat) death, could result in breakthroughs with far-reaching implications for our lives and our societies. In an era of augmented longevity, ageing may no longer be the inexorable final phase of human life.

Reaping the Next Longevity Dividend

Historical increases in life expectancy have led to significant benefits for society. Since 1840, human life expectancy has increased by about three months each year, or two to three years of increased lifespan with each decade.¹ This increase was achieved in a number of distinct phases marked by the addressing of specific healthcare issues and diseases, each resulting in a corresponding longevity dividend.

The first longevity dividend came from reducing infant mortality. By treating diseases such as smallpox, tuberculosis, typhoid and diphtheria, child and infant mortality fell significantly.² This allowed more children to reach working age, with significant productivity and economic gains. The second longevity dividend was and is still being reaped by tackling chronic diseases which tend to occur at middle age and beyond, such as cardiovascular diseases, diabetes and cancer. Through early health screenings, more effective treatments and public awareness campaigns to promote healthier lifestyle choices, individuals’ healthspans have experienced an increase estimated to be worth trillions of dollars in value.³

The mitigation of key causes of morbidity in each era was the source of the first two longevity dividends. The next longevity dividend will arise from addressing the next significant threat to morbidity: ageing-related illness and the ageing process itself. By 2030, the global population of those aged 60 years and above is projected to grow by 56%; by 2050, it will double in size. The potential dividends from tackling ageing-related illnesses could be dramatically significant.⁴ These dividends could come in the form of productivity gains through increased number of working years, and potential cost savings if the elderly stay healthy for longer.

The Road to Augmented Longevity

A confluence of developments across domains like technology, healthcare, engineering and genetic research suggests that we are on the brink of the next phase of longevity extension. Investments in anti-ageing research show keen interest and momentum: the global anti-ageing market was worth US$250 billion in 2016 and is estimated to grow to a whopping US$331.41 billion by 2021.⁵ The diverse range of anti-ageing or augmented longevity interventions also indicates a deep and perceptible shift away from the passive acceptance of ageing as the norm, to ageing as an obstacle to be overcome through technological innovation. Examples of these augmented longevity developments include:

Man walking with the help of a robotic exoskeleton

• Physical enhancements. Exoskeletons and other physical augmentations have an indirect but nonetheless powerful impact on healthspans. While they do not address the root causes of ageing and mortality, they can extend an individual’s physical longevity. For example, Cyberdyne’s Hybrid Assistive Limb (HAL) augments the physical strength of wearers and SuitX’s Phoenix exoskeleton lets paraplegics walk unassisted for four hours at up to 1.8 km per hour.

PARO, a therapeutic robot

• Social robots. Robot companions powered by artificial intelligence (AI) could help to extend cognitive longevity by keeping individuals mentally active and purposefully engaged. Many of these devices, such as PARO (a therapeutic robot), are already on the market and the impact of mass adoption over the next few years could be transformative.⁶ The growing awareness of an “epidemic of loneliness”, with attendant healthcare and social costs, make social robots a particularly important prospect for augmented longevity.⁷
• Smart wearables. This is part of a wider Quantified Self movement, in which the ubiquity of next-generation smart wearable technologies will help individuals monitor their own state of health, and gamify life-extending behavioural changes (for example, increasing motivation to exercise).⁸ The combined power of personalised data analytics, artificial intelligence and gamification techniques will significantly boost the ability to prompt and sustain behavioural changes, be it for caloric restriction, healthier diets or a more active lifestyle. While fitness trackers are already commonplace, their upgraded successors could be truly transformative due to the greater degree of customisation and personalisation of feedback and gamification which would become possible. Individuals respond differently to different incentives and the ability of the next generation of smart wearables to adapt to each unique user could have profound effects on healthspans.⁹

Metformin has been found to extend the lifespan of Type-2 diabetic patients

• Pharmaceutical drugs. Augmented longevity could be just a pill away, with current drugs showing great potential to extend healthspans. For example, Metformin, a cheap, safe drug used widely for type-2 diabetes, has already been found to extend the lifespan of type-2 diabetic patients relative to non-diabetic controls.¹⁰ Mice with metformin added to their diet have seen an approximate 40% increase in their mean lifespan.¹¹ In December 2016, the US Food and Drug Administration approved the Targeting Ageing with Metformin (TAME) study, which will study whether preventively administering metformin to healthy individuals can prevent or delay the onset of ageing-related diseases. TAME is a significant milestone since it is the first drug trial to broadly target ageing-related processes.¹² This paves the way for trials of other drugs that could extend healthspans and lifespans.

 

A 3D printed human heart

• Rejuvenation Treatments. There has already been success in regenerating muscles, tissues and organs through pluripotent stem-cell research, the 3D printing of organs and the growing and harvesting of human organs in pigs. The routine and sustainable replacement of aged body parts could soon be within reach. In 2017, biologists at the Salk Institute, succeeded in growing human stem cells in pig embryos. The resultant organ would be made of a patient’s own stem cells, mitigating the risk of immune rejection. Swiss scientists at ETH Zurich have also developed a functional beating heart made of silicone and based on a 3D mould.¹³
• Gene therapy. The successful use of the gene-editing technique CRISPR has enabled a host of interventions that may extend healthspans and lifespans at the most fundamental levels of human biology. In August 2017, scientists successfully corrected a genetic defect in newly created human embryos via CRISPR, demonstrating that gene editing technology could prevent the transmission of inherited diseases to future generations.¹⁴ As scientists gain a better understanding of the genetic processes behind ageingrelated diseases and the ageing process itself, genetic interventions may allow us to delay ageing, or eventually defeat it entirely.¹⁵

Taken together, these developments indicate that we are already living in the age of augmented longevity and we will live longer and healthier lives than our predecessors. This raises a number of significant implications.

Implications of Augmented Ageing

New possibilities for extending healthspan and longevity

The dominant narrative in Singapore has always been to promote active lifestyles, healthier diets, as well as early diagnoses and treatments in order to lengthen healthspans. However, augmented longevity technologies provide new possibilities.

First, gamification could be leveraged to spur individuals to maintain healthier lifestyles or post-treatment care. This, coupled with customised data analytics and feedback from AI-powered assistants, is where the next wave of longevity dividends will be reaped. Healthcare apps and their AI assistants could save more lives than hospitals in the near future.

Second, drugs and supplements taken to prevent ageing-related illnesses instead of to cure specific illnesses are a potential game changer. Instead of ageing as an inevitable biological process, the TAME trial suggests the potential for ageing-related processes to be targeted and blocked. Regular supplements to delay ageing could become as commonplace as Vitamin C tablets.

Ethical concerns and values-based conversations

New technologies and treatments present exciting possibilities but also raise ethical challenges.

First, in the early stages of adoption, these augmented longevity technologies are likely to be prohibitively expensive and may only be available to the wealthy. Ensuring fair and equal access for all will be an important issue for regulators to consider.

Second, it will be necessary to ensure that the clinical trials and marketing of new treatments are done ethically and do not exploit the vulnerabilities of those who are terminally ill and/or ageing. Scientists and regulators alike have urged caution in fixating on a specific gene or biological process as a key determinant, as ageing is still a complex process. There should also be public education around the efficacy of new treatments so that individuals are not misled by exaggerated claims of life-extension.

Third, the inter-generational compact between the young and the old will require careful management. New treatments will benefit the growing segment of seniors, while the costs could be borne by a shrinking proportion of younger workers, especially if social structures, such as retirement age, remain the same. If seniors stay healthy and remain in their jobs beyond current norms, maintaining sufficient opportunities for younger workers could also become a concern. Therefore, there will need to be values-based conversations on how to allocate national resources and opportunities between the competing needs of different generations (e.g., life-extension versus housing and education subsidies).

Moving away from age as a definitive marker

As new technologies lengthen cognitive and physical function, age becomes less meaningful as a marker of life stage and ability. Moreover, research has proven that that biological ageing, far from being a static and intractable process, is significantly plastic. This means that a decline in physical function is not tied to specific ages. A deeper and more textured understanding of ageing and longevity  is needed. Policies which are anchored on distinct ages as proxy indicators of ability, such as retirement ages, will need to be reviewed and updated to keep pace with advances in scientific research and technological innovations. For example, an experienced older worker empowered by exoskeletons may be equally or better able to function in a labour-intensive job,
compared to a younger worker.

Conclusion

Developments in augmented longevity challenge us to reframe our view of ageing and to strategically position ourselves to reap the next longevity dividend. We must anticipate fundamental disruptions to our assumptions about age, ageing and life stages. The sooner we invest in new ways of thinking around what it means to grow older and live longer, the better able we will be to harvest the fruits of living in a world where age is just a number.

NOTES

1. Lynda Gratton and Andrew Scott, The 100 Year Life: Living and Working in an Age of Longevity (Bloomsbury Publishing, 2016), 18.
2. Infant mortality fell from 43% in 1800 to 18.5% in 1960 and 4.3% in 2015. Source: The World Bank, “Mortality Rate, Under-5 (Per 1,000 Live Births), accessed May 20, 2017, http://data.worldbank.org/indicator/SH.DYN.MORT.
3. In the 1950s, only 13% of the world population at age 65 lived to age 85. However, in 2013, this figure increased to 43%. Source: United Nations, “Life Expectancy and Mortality at Older Ages”, Population Facts, December 2013, accessed May 20, 2017, https://www.un.org/en/development/desa/population/publications/pdf/popfacts/PopFacts\_2013-8\_new.pdf; The global economic burden of life lost due to non-communicable diseases is estimated to be between US$6.7 to US$43.4 trillion in 2030. Source: World Economic Forum and Harvard School of Public Health, The Global Economic Burden of Non-communicable Diseases (Geneva: World Economic Forum, 2011), http://www3.weforum.org/docs/WEF\_Harvard\_HE\_GlobalEconomicBurdenNonCommunicableDiseases\_2011.pdf.
4. United Nations, UN World Population Ageing Report 2015 (New York: United Nations, 2015), 8, http://www.un.org/en/development/desa/popuation/publications/pdf/ageing/WPA2015\_Report.pdf.
5. The full report can be accessed at Reuters, accessed November 10, 2018, https://www.reuters.com/.
6. PARO is an advanced interactive therapeutic robot designed to stimulate patients with dementia, Alzheimer’s and other cognition disorders. It was developed by AIST, a leading Japanese industrial automation pioneer. See PARO (website), accessed November 10, 2018, www.parorobots.com.
7. For a decade of an older person’s life, the extra economic cost of loneliness is calculated as 6,000 pounds. Loneliness is also linked to earlier death and higher risks of dementia. Source: Sean Coughlan, “Loneliness: The Cost of the ‘Last Taboo’”, BBC, September 22, 2017, accessed November 10, 2018 at: https://www.bbc.com/news/education-41349219.
8. Apple’s iOS HealthKit App has seven major categories of information (body measurements, fitness, me, nutrition, results, sleep and vitals) and 67 separate categories ranging from active calories to zinc levels. The SCiO spectrometer works with your smartphone to tell you the chemical make-up of food, allowing one to make better dietary choices. The latest Apple Watch Series 4 also boasts the ability to take ECG (electrocardiogram) readings.
9. Companies like Ayogo, Mango Health and Pact (funded by the founder of the popular game Guitar Hero) are just some examples of companies that have gamified healthcare and saved lives. Source: Yu-kai Chou, “Top Ten Gamified Healthcare Games that Will Extend Your Life”, accessed November 10, 2018, https://yukaichou.com/gamilfication-examples/top-ten-gamification-healthcare-games/.
10. C.A. Bannister, S.E. Holden, S. Jenkins-Jones, C. Ll. Morgan, J.P. Halcox, G. Schernthaner, J. Mukherjee, and C. J. Currie, “Can People with Type 2 Diabetes Live Longer than Those without? A Comparison of Mortality in People Initiated with Metformin or Sulphonylurea Monotheraphy and Matched, Non-Diabetic Controls”, Diabetes, Obesity and Metabolism 16 (2014): 1165–1173, https://pubmed.ncbi.nlm.nih.gov/25041462/; Metformin has no adverse effects unless overdosed. See Hamid Nasri and Mahmoud Rafieian-Kopaei, “Metformin: Current Knowledge”, J Res Med Sci 19 (2014): 658–664, http://jrms.mui.ac.ir/files/journals/1/articles/10000/public/10000-38736-1-PB.pdf.
11. Nir Barzilai, Jill P. Crandall, Stephen B. Kritchevsky, and Mark A. Espeland, “Metformin as a Tool to Target Aging”, Cell Metabolism 23 (June 2016): 1060–1065, http://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30229-7.pdf.
12. According to Dr Nir Barzilai, the risk of contracting an ageing-related disease past the age of 65 is about 9 per cent per year. Stephen S. Hall, “A Trial for the Ages”, Science 349, no. 6254 (September 2015): 1274–1278, https://science.sciencemag.org/content/349/6254/1274.
13. Biologists at the Salk Institute have succeeded in growing human stem cells in pig embryos. The resultant organ would be made of a patient’s own stem cells and thus reduce the risk of immune rejection. Source: Nicholas Wade, “New Prospects for Growing Human Replacement Organs in Animals”, The New York Times, January 26, 2017, accessed May 20, 2017, https://www.nytimes.com/2017/01/26/science/chimera-stemcells-organs.amp.html; Swiss scientists at ETH Zurich developed a functional beating heart made of silicone using a 3D mould. See Luke Dormehl, “Swiss Scientist just 3D Printed an Artificial Heart that Beats Like the Real Thing”, Digital Trends, July 14, 2017, accessed November 13, 2017, https://www.digitaltrends.com/cool-tech/3d-printed-silicone-heart/.
14. Clive Cookson, “Scientists Mend Genetic Defect in Human Embryo for First Time”, Financial Times, August 3, 2017, accessed Aug 30, 2017, http://www.ft.com/content/ba9c41a0-76d5-11e7-a3e8-60495fe6ca71.
15. There are many ongoing studies on the genetic causes of ageing. For example, George Church, a Harvard geneticist, has culled 45 promising gene variants from humans who have lived to 110 years old as potential ageing genes.