JOHANNESBURG - After the establishment of the new constitution of the US, Benjamin Franklin wrote a letter in 1789 stating that nothing in this world is certain, except death and taxes. But now it seems that some scientists are not that sure about death anymore.
For a long time people have strived to live longer with the result that one of the important medical frontiers today is to extend the human lifespan. In June 2018, the World Health Organisation published the 11th edition of its International classification of diseases, which contained a seemingly insignificant new addition, namely, “Code MG2A: Old age”.
However, this minute inscription could be one of the most important inclusions in human history and could potentially lead to the development of new drugs designed to treat one of the world’s most universal ailments – ageing, which has been known as a major contributing cause to most other age related illnesses.
Although regulatory changes will be necessary, this new approach to ageing would make it possible for medical doctors to eventually prescribe medicines to slow the condition of ageing and ultimately death.
Notwithstanding the absence of the necessary regulatory environment, bio-medical research has been making considerable progress over the past few years. Since Clive McCay discovered in 1934 that the restriction of caloric intake through limited diets extended the live of rats, Michael Rose from the University of California, Irvine, in 1981 bred a strain of fruit fly that can live four times longer than normal.
In 1993 Cynthia Kenyon and her team from the University of San Francisco discovered the daf-2 mutation, which doubled the life span of roundworms (nematodes).
In addition to numerous genetic studies, it was inevitable that drugs would be developed to slow ageing and extend human life. In 2006 Matt Kaeberlein from the University of Washington, demonstrated that rapamycin – a drug isolated from soil bacteria on Easter Island – could increase the life span of yeast cells. It was later proven that rapamycin increases the life span of mice by 24 percent.
In 2016 Nir Barzilai, director of the Institute for Ageing Research at the Albert Einstein College of Medicine discovered that metformin, could prolong the life span of silkworms. Metformin (marketed under the trade name Glucophage) is a well-known and effective first-line medication used by millions of people with type 2 diabetes.
Over the last five years researchers discovered that this now inexpensive generic and widely available drug influences several metabolic and cellular processes closely associated with the development of age-related conditions. Except for metformin’s lowering of glucose levels, it also has an effect on inflammation, ameliorates DNA and cellular damage, improves muscle tissue health, preserve cognitive function, and reduce mortality.
The reduction of chronic damage resulting from inflammation eventually could have positive benefits for ageing, cardiovascular disease, Alzheimer’s disease and cancer.
Numerous animal studies have proved that metformin may delay the ageing process and have a neuroprotective role. Therefore Barzilai and his team are taking their research one step further to demonstrate metformin’s ability in humans to delay the onset of comorbidities related to ageing, thereby reducing the period of morbidity at the end of life and increasing the health span of people.
Dr Tze Pin Ng and colleagues from the National University of Singapore published their research in The Journal of Alzheimer disease, indicating that metformin was inversely associated with cognitive impairment.
After reviewing thousands of medical records, Dr Scherrer form Saint Louis University in June 2019 published an article showing that African Americans older than 50 years and treated with metformin had a much lower risk for dementia. It is thus becoming clear that metformin could play an important role in deferring the onset of Alzheimer’s disease and dementia.
In an observational study Dr Bannister from Cardiff University found patients with type 2 diabetes treated with metformin monotherapy lived significantly longer than patients treated with alternative medicine or even a large control group without diabetes or medication. This research implies that metformin may have benefits even for non-diabetes.
However, despite all the benefits of metformin, we are still years away from being able to state with absolute confidence that metformin prevents ageing.
Numerous new start-ups are currently searching for life extending drugs, such as the biopharmaceutical company resTORbio that is researching a drug known to enhance immunity against age-related viral infections. The same drug may in fact also prevent numerous other manifestations of ageing.
Calico (an acronym for California Life Company) is a secretive biotech company in the USA that is a division of Alphabet (the Google parent company). Although the company states that they focus on health and wellbeing and the challenge of ageing, it is well known that according to Art Levinson, the chief executive, the mission of the company is in fact to achieve human immortality. The company therefore researches therapies for age-related illnesses in an attempt to extend human life span.
In November last year Calico hired Dr Garret FitzGerald, an Irish professor, who is an expert on “molecular clocks” or the idea that genes operate on 24-hour cycles, which could be altered to slow down cell damage and delay Alzheimer’s.
The California start-up Unity Biotechnology is researching drugs that could remove the “zombie-like” cells that accumulate with age, while CohBar is attempting to harness the power of mitochondria-based therapeutics aimed at slowing ageing’s effects.
A research team from Mayo, Wake Forest and the University of Texas, San Antonio, recently announced promising results from early human trials with senolytics – agents that selectively destroy senescent cells or induce cell death.
The researchers claimed that they were able to stop Alzheimer’s disease in it tracks.
Without doubt, anti-ageing medicines are now amongst the top ten disruptive innovations. Contrary to popular belief, there is no biological law that determines that people must age. Ageing is currently the biggest risk factor behind most of the age-related diseases. Quite often when one disease in older people is addressed through treatment and it improves, another disease will often replace it, unless ageing itself is targeted.
Ageing research is therefore focusing not only on extending human life, but the eradication of disease itself.
Although the processes for extending life are complicated, the metformin research has shown that sometimes it may be as simple as repurposing medications that are already available and affordable.
If we ask a person to point out persons who are 70 years old it is quite easy, since we all know the biology of ageing. But to think that it is normal and that we cannot do anything about it, is an error.
Research shows that we can intervene in ageing, even in the later phases. People 50 years or older most probably have a brighter future since it is possible that they would not be ageing as fast or poorly as their parents.
Over the years cosmetic companies have through clever marketing convinced women to buy moisturisers and other anti-ageing cosmetics. Most pharmacies would have at least fifty or more products that falsely claim to be anti-ageing.
Unfortunately most creams achieve very little and the vitamins only give users expensive urine. Currently this market is worth hundreds of billions of rand per year. Just imagine how much a pill that could really slow ageing or stop death could be worth. In the era of the fourth industrial revolution nothing seems to be impossible – everything could be hacked, including the human body.
Although some people might frown on the possibility of a tablet extending human life, the situation is not unfamiliar. Before Louis Pasteur enlightened the world with his germ theory in the 1880s, people believed death by disease was inevitable.
The discovery of penicillin in 1928 totally changed this believe. So why not envisage a time in the future when scientists could stop ageing and age-related illnesses and offer a better quality of life? Economically it would bring welcome relieve to overextended healthcare services and the ill-planned National Health Insurance of South Africa.
The technologies being developed now would not only give us extra years of life, but also extra years of youth.
In the years to come we will begin to understand that ageing is something that can be reversed.
Whether we will live long enough to benefit from innovation in this sector – or be the last generation to live a relatively short life – depends on current innovation, human trials and regulatory changes to make it possible.
Perhaps, it is indeed time that we start treating age as a disease.
Professor Louis C H Fourie is a futurist and technology strategist.