What does it mean to age in the accompaniment of science and technology? By Pearly Neo
Given the rapid advancements in medical, nutritional knowledge and technology in this day and age, the fact that the average age of many populations around the world are also rising in a parallel manner comes as no surprise. The World Health Organisation data have shown that in 1900, the average global life expectancy was 31 years - as of 2015, it has increased to 71.4 years.1
Here in Asia, two very clear cut examples of ageing populations are that of Japan (2015 data indicated the average life expectancy for males: 80; females: 87;2 26.7% of population aged 65 and older 3 ) and Singapore (average life expectancy for males: 80; females: 86;4 13.0% of population aged 65 and older in 20175 ) – also two countries that are simultaneously acknowledged to be amongst the most developed and technologically-advanced countries in the region.
But what exactly does it mean to age in the accompaniment of science and technology?
The science behind ageing
Biologically, ageing is inextricably linked to senescence, and herein both cellular senescence and organismal senescence need to be mentioned. Cellular senescence is the process where cells cease dividing and undergo distinctive phenotypic alterations6 that arrest proliferation, a phenomenon that is theorised to be closely related to telomere attrition. Telomeres are repeated nucleotide sequences that are found at the end of chromosomes, protecting the chromosomes, but truncating every time the chromosome is replicated. In humans, this sequence is TTAGGG, and will shorten over time from 11 kilobases at birth,7 to less than 4 kilobases in old age.8 Cellular senescence as a whole is believed to lead to organismal senescence.
Science in ageing diseases
Research on the specific reasons for ageing have yet to reach a formal conclusion, but it is clear that as a person ages, various symptoms and effects will be displayed. Chief, and most worrying, among these is the emergence of various ageing-related diseases, e.g. dementia,9 arthritis, atherosclerosis,10 mobility loss and many more. Along with a rapidly increasing elderly population, will come a boom in the occurrences of these diseases.
Dementia is among the most perturbing of these, because it not only has no cure, but also causes the patient to exhibit some of the most devastating symptoms. A gradual, long-term and usually permanent decrease in the ability to think and remember is the principal and most distressing symptom, usually accompanied by emotional and motivational issues, especially when dealing with Alzheimer’s disease, which in itself makes up 60% to 70% of all dementia cases, affecting around 50 million individuals worldwide.11
Today, although there is no way to treat the root cause of dementia as of yet, science has allowed for intensive research to be conducted on the various presentations of dementia. For example, the biochemical and pathological basis of Alzheimer’s disease has been clearly delineated, thus it is said to be closely related to the aggregation of abnormally-folded β-amyloid and tau proteins in the brain.12 Insights like these have allowed for dementia to be classified as a degenerative disease, and for treatments targeting the slowing of its progression, or at least the treatment of its symptoms, to be developed. Among these is bapineuzumab, a monoclonal antibody that targets β-amyloid removal in mild to moderate patients.13 If compared to back in the Dark Ages, when biotechnology was mostly a mystery and where many dementia patients were taken to be witches and burnt at the stake,14,15 it can surely be said that the consequences of ageing in the present day are much less abhorrent.
A more physical representation of ageing though, are the various aches and pains that the elderly tend to experience as they age, as well as an increased risk of developing chronic diseases. For the former, arthritis is one of the most common causes, and encompasses a group of over 100 different chronic and debilitating arthritic disorders.16 For the latter, atherosclerosis has been classified as an ageing disease, because increasing age is considered an independent risk factor in developing atherosclerosis, and this disease is also closely associated with the increased risk and comorbidity of cardiovascular conditions.
In the past, it would have only been natural for the older generation to just maintain a ‘just live with it’ attitude to the above, but today’s technological and pharmaceutical developments have allowed for both the relief of painful symptoms, as well as the alleviation of disease risk factors. From NSAIDs to opioids, pain-relief medications of differing strengths are widely available worldwide. Though extended use is unadvisable due to possible side effects, temporary usage in order to suppress debilitating pain offers elderly patients a chance to function normally during the process of recovery instead of having to just grit their teeth in prolonged suffering. Even newer methods like electric therapy TENS (transcutaneous electrical nerve stimulation) have also been shown to be independently effective in some cases.
Likewise, various treatments are also available to delay - or in some cases, reverse – the effects of atherosclerosis, hence also effectively reducing the risks of the associated cardiovascular diseases. Drugs from cholesterol medications to ACE inhibitors to beta blockers are all aimed at treating the affected arteries and preventing further damage. In serious cases, surgical procedures like angioplasty or bypass surgery are also available, and have saved the lives of many aged patients.
Science in ageing nutrition
The treatment of diseases aside, science and biotechnology in particular have also played a significant role in enabling people today to live much longer and healthier lives via nutritional improvement. From a general perspective, particularly in crop production, this is exhibited primarily in two ways: First, in the usage of biotechnology to improve food security and production, whether by increasing yields, production, or harvesting.17 All of these ensure a much more guaranteed supply of food worldwide, which both directly and indirectly helps in assuring that elderly and frail populations are less nutritionally deficient. Secondly, many different types of crops have been bioengineered and fortified with various types of nutrients, which in turn addresses the issue of malnutrition in the elderly.
The issue of malnutrition in the elderly is a tricky one, particularly as it can range through the extreme ends of the nutritional spectrum, from under-nutrition to over-nutrition, depending on many factors from socio-economic status to geographical location. In dealing with over-nutrition leading to issues like obesity and diabetes in the elderly, the impact that biotechnology can make is somewhat more limited at the moment, mostly surrounding nutrient-related efforts like developing rice with a low glycaemic index,18 spearheaded by big institutions like the Philippines-based International Rice Research Institute (IRRI) and the Australia-based Commonwealth Scientific and Industrial Research Organisation (CSIRO).
Under-nutrition encompasses many more complicated factors, ranging from painful chewing due to poor dental health, to changes in taste buds or appetite due to medication side effects. More often than not, these will lead to a decrease in food intake, causing malnutrition. As such, one of the most direct ways of addressing this issue is to offer the elderly food that is more nutritionally dense, and biotechnology has come a long way in providing offerings in this arena.19 Good examples are soybeans that contain high levels of oleic acid, a monounsaturated ‘good’ fat, as well as maize with increased lysine, an essential amino acid. Another interesting example is that of the delayed-ripening tomato, which allows for the tomatoes to remain on the vines for a longer period of time, enhancing flavour and texture, traits that would appeal to elderly consumers.
Taking this from another perspective, technology has also allowed for the production of foods that cater specifically to the elderly, and Japan is a leader in this area. With the world’s highest proportion of people aged 65 and above,20 it is no wonder that progress in this area has reached milestone after milestone in the past few years. No other country has as wide a selection of purees, jellies, and various other soft-food products with nourishment catering to the elderly, available not only in nursing homes but also in regular supermarkets and stores nationwide. An example is that of Japan’s ‘Engay’ foods, customised easy-to-swallow foods that specifically target the elderly population, aiming to reduce the incidences of accidental choking.21
To discuss ageing is to discuss mortality, and to discuss mortality in the same breath as science is to consider just how far science can go in reducing mortality. Though the answer to this still remains a mystery as of yet, much effort is ongoing to uncover the specific mechanisms of ageing, and to battle it.
Most recently, in 2017, scientists discovered a genetic mutation leading to what is dubbed the ‘anti-ageing gene’ in an Old Order Amish family. The gene harbouring the mutation is SERPINE1,22 which regulates the PAI-1 protein responsible for dissolving blood clots. As such, a recessive mutation causes a genetic bleeding disorder – but a single-gene mutation has very different effects, such as 10% longer telomeres, lower rates of diabetes, and a 10% longer lifespan. PAI-1 is known to contribute to the cellular senescence process.23
From a business point of view, the business of anti-ageing science is a big one, and companies like Unity Biotechnology24 make their living by specifically targeting and battling the ageing process. Unity’s specific focus is also on the cellular senescence process, specifically on the selective elimination of senescent cells to prevent, halt or reverse ageing-related diseases. The company has created 13 FDA-approved senolytic medications targeting just this without affecting normal cells.
In terms of drugs, anti-ageing drugs have been a topic of discussion in the field for some years, but two of the most popular potential candidates so far are the diabetes drug metformin,25 and the NAD+ precursor NMN.26 Said to be able to extend lifespan up to 120 years, metformin is believed to prolong life by enhancing adenosine monophosphate-activated protein kinase (AMPK) enzyme activity, which in turn mimics calorie restriction benefits. Calorie restriction is one of the most documented methods in the realm of stopping/reversing ageing. NMN on the other hand focuses on repairing DNA damage, particularly that due to radiation or old age, by enhancing the activity of DNA repair protein poly(adenosine diphosphate–ribose) polymerase (PARP1). As such, though the very idea sounds like it is straight out of a science fiction fantasy, it may very well be a mere number of years before a true-anti-ageing drug is formulated, and ageing becomes obsolete in the age of science.
- van Deursen, J.M. (2014). The role of senescent cells in ageing. Nature, 509(7501): 439–446. doi: 10.1038/nature13193
- Okuda, K., Bardeguez, A., Gardner, J.P., Rodriguez, P., Ganesh, V., Kimura, M., Skurnick, J., Awad, G. & Aviv, A. (2002). Telomere Length in the Newborn. Pediatric Research, 52, 377–381. doi:10.1203/00006450-200209000-00012.
- Arai, Y. et al. (2015). Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. EBioMedicine, 2(10) , 1549 – 1558. DOI: https://dx.doi.org/10.1016/j.ebiom.2015.07.029
- Larson, E.B., Yaffe, K., & Langa, K.M.(2013). N Engl J Med 2013; 369:2275-2277. DOI: 10.1056/NEJMp1311405.
- Wang, J.C., Bennett, M. (2012). Circulation Research. 2012;111:245-259. https://doi.org/10.1161/CIRCRESAHA.111.261388.
- Murphy, M.P. & LeVine, H. III. (2010) J Alzheimers Dis.; 19(1): 311. DOI: 10.3233/JAD-2010-1221.
- Vandenberghe et al. (2016). Alzheimer's Research & Therapy, 8:18. https://doi.org/10.1186/s13195-016-0189-7
- Spanos, N.P. & Gottlieb, J. (1976). Ergotism and the Salem Village Witch Trials. Science, 194:1390—1394. Retrieved from: https://people.umass.edu/dcooley/FYS_articles/Spanos%20&%20Gottlieb%20Salem%20rebuttal%20Science%2076.pdf
- Feldman, H. (2007). Atlas of Alzheimer's Disease. Retrieved from: https://books.google.com.my/books?id=X5LgkgxgoTMC&pg=PA2&lpg=PA2&dq=%22dementia%22+witch+trials+17th+century&source=bl&ots=q3WeiWiOD9&sig=nLdjGyl0ZH2Y_7YsXAEdgAe8ltE&hl=en&sa=X&ved=0ahUKEwis-K_83OPYAhXMpI8KHS5FC-UQ6AEINjAF#v=onepage&q=%22dementia%22%20witch%20trials%2017th%20century&f=false
- Brennan-Olsen, S.L. et al. (2017). BMC Musculoskelet Disord. 18: 271. doi: 10.1186/s12891-017-1624-z.
- Junne, G. Biotechnology: the impact on food and nutrition in developing countries. Retrieved from: https://www.fao.org/docrep/U3550T/U3550T0H.HTM
- 18.Fitzgerald, M.A., Rahman, S., Resurreccion, A.P. et al. (2011). Identification of a Major Genetic Determinant of Glycaemic Index in Rice. Rice, 4: 66. https://doi.org/10.1007/s12284-011-9073-z.
- Khan, S.S., Shah, S.J., Klyachko, E., Baldridge, A.S., Eren, M., Place, A.T., Aviv, A., Puterman, E., Lloyd-Jones, D.M., Heiman, M., Miyata, T., Gupta, S., Shapiro, A.D., Vaughan., D.E. (2017). A null mutation in SERPINE1 protects against biological aging in humans. Science Advances, 3(11). DOI: 10.1126/sciadv.aao1617.
- Campisi, J. & d'Adda di Fagagna, F. (2007). Cellular senescence: when bad things happen to good cells. Nature Reviews Molecular Cell Biology, 8, 729–740. doi:10.1038/nrm2233.
- Li, J. Bonkowski, M.S., Moniot, S., Zhang, D., Hubbard, B.P., Ling, A.J.Y., Rajman, L.A., Qin, B., Lou, Z., Gorbunova, V., Aravind, L., Steegborn, C., Sinclair, D. (2017). A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science 355(6331), 1312-1317. DOI: 10.1126/science.aad8242
About the Author
Pearly is an experienced writer and editor with a particular interest in the food, travel and biomedical science fields. She was previously the Editor for the MIMS Today, Asia Food Journal and PharmaAsia portals and publications, and her articles have been regularly featured in both print and digital media.