Written by Attiya Anna Abbas, edited by Ryan Khan and Daniele Guido.
How does the world currently perceive ageing?
Ageing is simply defined as ‘growing older’. ‘Growing older’ is something I believe many of us have accepted as our natural state, as all living things arise fresh, then age, weaken and finally die and that is largely considered as just the way things go. However, I believe ageing entails far more than just ‘growing older’.
With old age our susceptibility to many age-related diseases heightens, and that includes cancer, diabetes, auto-immune diseases and infections. In 2018, the World Health Organization (WHO) added an extension code and updated the International Classification of Diseases for ‘age-related’ diseases (ICD-11), which are recognized as pathological processes that lead to an organism’s loss in adaptation – this tends to worsen with old age [1]. Therefore, from January 2022 when every country in the world will be encouraged to report using the ICD-11 code, it will be possible to be diagnosed with a condition called old age. Professor David Sinclair, the scientist at the frontier of ageing research at Harvard University [2], eloquently defines ageing as being the state that brings one to the precipice of the cliff– at that point an individual tends to become predisposed to many diseases that bring about their fall from the cliff.
So, what if we could tackle this initial factor, that is ageing to prevent us from even being brought to the precipice of the cliff? Many researchers across the world are in the middle of doing so and their achievements could have tremendous consequences for all of us in the future.
Why should we change the way ageing is defined?
The WHO has predicted that 22% of the world population will surpass the age of 60 by 2050, which is an increase from 12% in 2015 [3]. Although increased life expectancy indicates many positives, including improvements in healthcare, diet, socioeconomic status to name a few, it also brings some concerns. A rise in life expectancy is aligned with a global increase in ill health in old age, due to a heightened burden of non-communicable diseases and age-related conditions that impact the healthcare system of a country.
Although ageing is often depicted as a risk factor for developing disease rather than a disease itself, ‘accelerated ageing diseases’ such as Werner syndrome, and Dyskeratosis Congenita, which are conditions where the ageing process occurs more swiftly, are recognized as diseases [4]. If by 2022 more countries will deem ageing as a disease then that would also suggest ageing is a condition that can be treated [5].
If ageing is a disease, how can it be treated?
Over the last two decades, biomedical scientists have been able to improve the health and lifespan of model organisms e.g. worms, flies, rodents etc., by targeting the underlying processes of ageing [6]. For example, nicotinamide adenine dinucleotide (NAD) boosters such as Nicotinamide Mononucleotide (NMN), the precursor to NAD, when administered to mice have been found to increase their lifespan. NAD declines with age, which in turn reduces the activity of sirtuin, a family of proteins that are critical in responding to stress signals such as DNA damage. Therefore, with age the reduced sirtuin activity leads to a higher risk of senescence being induced in our cells, losing their ability to participate in several physiological processes, like tissue repair. Professor David Sinclair and his research group at Harvard University found that when NMN was given to older mice, it enhanced their mitochondria activity and gave them the physical endurance of their younger counterparts.[2] Research has shown supplementation of NAD precursors in the human diet to augment NAD levels can be beneficial, such as for boosting energy, cognitive function, improving athletic performance to name a few [2,7].
For example, a phase II randomised controlled trial (RCT) on an NAD precursor showed positive effects of increased NAD levels on a small sample of human volunteers which may be expanded on in the future if the study progressed to phase III [7].
Therapeutics in development to target the ageing process
Many biotechnology companies across the world are developing and advocating for a new model of healthcare to be delivered by healthcare systems, doctors and pharmaceutical industries. This would allow for ageing to be diagnosed as a disease and thus enable therapies to be developed to prevent rather than treat several life-threatening conditions from cancer, to autoimmune diseases etc. The biopharmaceutical company resTORbio has been working on a drug that can improve immunity against age-related viral infections. This compound may be able to treat other age-related diseases [8]. Calico is a startup working on ways to expand on the anti-ageing work conducted by geneticist Cynthia Kenyon. Unity Biotechnology is focusing on developing drugs, senolytics, that can eliminate senescent cells that accumulate with age and are responsible for the degenerative changes we perceive as ageing and age-related disease [9].
Metro Biotech is developing a wide array of pharmaceuticals for age-related diseases that seemingly emulate a healthy lifestyle. CohBar is planning to utilize mitochondria-based therapeutics to slow ageing effects. In addition, the UK based biotechnology longevity company, Juvenescence, have developed a supplement, ‘Metabolic Switch’ in collaboration with the Buck institute for Research on Aging. This compound increases the levels of ketones in the blood to generate a state of ketosis which would last several hours. Ketone utilization means more readily available energy which would have tremendous benefits in protecting an ageing brain, an organ that consumes over 20% of the body’s energy [10,11]. Notably, the American Federation for Aging Research has planned a large clinical trial to study if metformin, which is widely used to treat type 2 diabetes, could be used to delay the onset of age-related diseases such as cardiovascular diseases, cancer and Alzheimer’s disease. The trial will be spread over several years to aim for maximum results in order to acquire FDA approval to treat ageing and thus that that the condition of ageing is a treatable composite of age-related diseases.
Summary
On a final note, to many researchers including myself who consider ageing as a disease, this seems to be the most rational definition. For example, we would argue a critical flaw with the current healthcare system is not recognizing ageing as such; therefore, not viewing it as an underlying cause for chronic diseases that affect the elderly. This means that the healthcare system is reactive rather than proactive, treating individuals with chronic conditions usually when it is too late. If ageing was recognized as a disease this would allow doctors to prepare and prevent conditions arising before they occur. When people hear that our lifetimes are being extended, they resist the idea of being frail or sick for more years, which is worrisome. However, technologies are being developed to not only extend lifespans, but to make those years comparable to our youth in that our energy levels, and cognitive function would not drastically change. Moreover, in terms of an economical perspective, treating the driver of many diseases may not be as costly as you would think. In 2005, a study by economist Dana Goldman and colleagues at The RAND Journal of Economics estimated that the cost of an innovative medicine to prevent diabetes would be $147,19, for cancer treatment $489,809, and for an anti-ageing compound to extend human life by decades $8,790 [2]. This highlights that there really is no cheaper way to challenge the healthcare crisis than to tackle ageing at its core.
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