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2020 was a historic year. It was a challenging year and a disappointing one for many people. This was all due to a novel virus, SARS-CoV-2, but, unlike in the past, this year we also managed to study the structure of the virus, find treatments for it, and finally create vaccines against it.
2020 has also been a landmark year for biotechnology. We witnessed Nobel prizes being awarded for the discovery and cure for hepatitis C, as well as for precision gene editing using CRISPR. In addition to these groundbreaking achievements, our research team has tracked major developments all through the year in longevity biotechnology and its progress in the rest of the world.
This article outlines our research by summarizing the top 10 innovations that will accelerate human health and longevity. These technologies, treatments, or diagnostics should enable humans to live longer and healthier lives, and/or differentiate the biological age of an individual from their chronological age to better inform health decisions.
We have ranked these innovations according to their ability to improve and increase health and longevity in the largest number of people. We use the following four criteria to highlight the unique impacts of each of the 10 longevity innovations of 2020:
Number of people impacted: The approximate total number of people who, within the next decade, are in a position to directly benefit from this innovation.
Years of additional life (per person): Our estimation of the number of years of life gained by individuals who stand to benefit most from this innovation.
Technology: The technology or platform involved in this innovation.
Specific trial, company, or product: The specific research, companies, or products that best exemplify this innovation.
Why we think this is revolutionary:
Automation and machine learning have begun and will continue to radically change the way science and medicine is conducted. On the one hand we are finally beginning to see the automation of laboratory work. Scientists currently spend a huge chunk of their time in the lab carrying out laborious tasks that require no scientific training. Automation of these tasks allows scientists to spend more time designing experiments and analysing results, while also improving experimental reliability and reproducibility to raise the quality of scientific research overall.
On the other hand we have machine learning. Machine learning has opened up entirely new opportunities in both research and clinical settings. It has allowed us to make huge strides in the prediction of 3D protein structures, exemplified this year by Google DeepMind’s AlphaFold system. The sequence of amino acids from which a protein is made ultimately decides how it will fold into a three dimensional shape, which in turn determines its function. However, predicting protein shape computationally has been a massive challenge due to the immense number of possible ways a protein could fold. AlphaFold has largely overcome this challenge, enabling structure to be predicted with very respectable accuracy with its attention based neural network system. This has the potential to save a great deal of laboratory time and money, and will also open the door to new means of drug discovery.
The ability of machine learning to analyse vast datasets has already been used to screen millions of molecular structures to identify new drugs, some of which are entering clinical trials. Machine learning has been used to predict the development of diseases years before they are diagnosed, often with more accuracy than current methods. This has the potential to be hugely impactful as it can improve early detection, which is critical to the outcome of many age-associated diseases. Machine learning also brings the promise of personalised medicine closer, as it provides the means to leverage large datasets in order to tailor treatments on an individual basis.
Why we think this is revolutionary:
We live in an unprecedented age of instant communication and information transfer. Despite this, most health monitoring does not leverage this technology, and relies instead on deliberate action by a patient. This means that often, by the time a health problem is detected, it is already serious enough to have caused a doctor’s visit. Wearable health monitoring devices have the power to solve this problem by allowing for the preventative healthcare that we have known we needed for decades. They also enable users to be more aware of how their lifestyle is affecting their health, which may aid them to avoid developing health conditions in the first place.
The Apple Watch Series 6 and the Samsung Galaxy Watch 3 released this year these watches can detect atrial fibrillation, falls, provide an electrocardiogram (ECG), and continuously monitor your resting heart rate, heart rate variability, blood oxygenation levels, and your sleep habits. The Samsung Galaxy Watch 3 can also measure your blood pressure. Launched this year, the Amazon Halo wristband is the first wearable device that attempts to decipher, measure, and provide feedback about emotions from daily conversations in real time.
2020 has also seen improvements in glucose monitoring technology with Freestyle Libre 3. These devices are now able to measure resting heart rate, heart rate variability, blood pressure, blood oxygen and many other important (and often less obvious) health readouts like time spent sitting per day. Better still, they are becoming increasingly affordable, and when combined with machine learning, could better the health of a vast number of people while fundamentally changing the way diseases are diagnosed.
Why we think this is revolutionary:
Biological, or epigenetic, clocks are biochemical tests which can predict biological age based on DNA methylation. Epigenetic clocks represent a useful diagnostic tool, which can help to more accurately identify an individuals risk of developing an age-related chronic disease years before current detection methods. Through the development of specific clocks for particular tissue types, and the use of big data and machine learning techniques, over the course of 2020 the accuracy of these clocks have been progressively improved.
In almost all chronic diseases, the survival will depend on the disease stage at which the disease is diagnosed and treated. Individuals diagnosed in an earlier stage will tend to have longer survival than those diagnosed in a more advanced stage. Consequently, if an early detection program tends to diagnose individuals in an earlier stage, compared with the stage they would have been diagnosed by usual care, there could be a gain in survival resulting in a reduction in mortality. This is called stage shift and it is where epigenetic clocks, with their ability to predict risk of age-related chronic disease years before the symptoms occur, could have a huge impact on human longevity.
In this particular study early identification and appropriate medical care may delay 34 cases of end-stage kidney disease and prevent diabetes-related complications, 210 cases of diabetes, and 3 cases of late-stage colorectal cancer over 5 years per 1000 cases identified.
Why we think this is revolutionary:
Hyperbaric oxygen treatment (HBOT) involves breathing in oxygen in a chamber where atmospheric pressure is raised up to three times higher than normal. This type of treatment is usually used to treat decompression sickness or sporting injuries.
However, a study published in October this year found that HBOT had a considerable impact on telomere length. Telomeres are short protective caps on the end of the chromosomes, designed to prevent damage to the DNA during cell division. telomeres are degraded and get shorter, inducing cellular senescence and aging.
The shortening of telomeres and resulting cellular senescence has been extremely well documented as two crucial molecular characteristics of aging. There have also been a multitude of animal studies that have found that an increased rate of telomere shortening is associated with a shortened lifespan, and by increasing telomere length these organisms experience significant life extension. Ine study found that doubling the telomere length of mice resulted in a 12.5% increase in lifespan.
Excitingly, the study found that the treatment increased the telomere length of four different types of immune cell; T helper, T cytotoxic, natural killer and B cells, by 20-38%, in humans. This could confer a rather significant extension of lifespan, and importantly, HBOT is a treatment that we, and, we are sure the rest of the medical community, would deem as extremely safe.
Why we think this is revolutionary:
While this line of research has not yet provided us with an increase in lifespan or human health, there is good reason to be hopeful that it will in the near future. It is very clear from animal research that factors in the blood control the ageing process. In studies published this year, treating rodents with young blood or even simply diluting old blood were shown to have rejuvenating effects. These not only included reduced markers of ageing like cellular senescence and inflammation, but also led to a significant reduction in measured biological age. The challenge now is to identify which of the countless factors found within blood are important, and to study whether they have any effect in humans. Fortunately, this year has also provided us with a promising lead in the form of the anti-hypertensive protein Klotho, and some companies such as Alkahest are currently conducting multiple clinical trials for potential anti-ageing blood treatments.
Why we think this is revolutionary:
Senolytic drugs are designed to target senescent cells – cells that have reached their division limit and have halted their replicative cycle. These cells build up as we age, and contribute to age-related diseases by releasing signals that harm surrounding tissues. The world’s two biggest killers, cardiovascular disease and cancer, cut off roughly 15 years of life. Both are driven in part by senescent cells.
Senolytic research in humans is still relatively young, and some senolytic trials have been met with failure or setbacks this year. Most notably, Unity Biotechnology announced the failure of their phase II trial of senolytics to treat knee osteoarthritis. Such setbacks are expected and need not be seen as complete failures, as they help improve our understanding of senolytics and how they can be made to function in humans. In this case, it may be that local administration of senolytics is ineffective as senescent cells throughout the body can contribute to disease. It may also simply be that Unity’s specific target in this trial is not particularly effective.
Despite this result, we still believe that senolytics have the potential to greatly improve human health and longevity, and that progress is being made towards this goal. Preliminary results from last year suggested that senolytics can reduce senescent cell burden and improve physical function in humans with idiopathic pulmonary fibrosis. Multiple clinical trials (see below) of senolytics in a variety of age-related conditions have launched in 2020, and we eagerly anticipate their results within the next 2-3 years. Until then, however, it’s still very much uncertain how many years of additional life these drugs might grant us.
Why we think this is revolutionary:
Sickle cell disease results from an inherited genetic mutation that results in abnormal haemoglobin (the protein in red blood cells that carries oxygen). This causes red blood cells to distort into an inflexible sickle shape, which can then block blood vessels to cause hypertension and organ damage. It is estimated that sickle cell disease shortens life expectancy by around 22 years. As red blood cells are produced by haematopoietic stem cells in the bone marrow, the only cure for sickle cell disease has been stem cell/bone marrow transplant from a healthy donor, but this comes with its own set of risks including transplant rejection by the immune system.
It is now becoming possible to treat sickle cell disease using gene therapy. Stem cells are taken from the patient, and RNA-based gene therapy is used to prevent the expression of a gene called BCL11A. This is the gene that controls the production of the adult form of haemoglobin – the one that carries the sickle cell mutation. In its absence, red blood cells will instead produce foetal hemoglobin, which is produced by babies and does not cause sickling. These altered stem cells are then used to replace the patient’s current stem cells.
As of October this year, six patients had been followed for 6 months or more following gene therapy. Stable foetal haemoglobin production was achieved in all evaluated patients, and clinical manifestations of sickle cell disease were reduced or absent during the follow-up period, which is a very promising finding. Within the next decade, we hope to see ex vivo gene therapy approaches continue to yield results for the treatment of monogenic diseases and beyond.
Why we think this is revolutionary:
Our microbiomes are made up of the populations of microorganisms that live on and in our bodies, such as on the skin or in the gut. The past two decades has seen a boom of research demonstrating that shifts in microbiome bacteria populations have a causal impact on the risk of developing age-related diseases such as diabetes, cancer, Alzheimers and cardiovascular disease. 2020 has been the year where we have seen some of this research manifest itself onto the consumer market in the form of treatments.
Pendulum, a US based pharmaceutical company, put the first FDA approved microbiome therapy for an age-related disease – type 2 diabetes – up on the market earlier this year. Pendulum glucose control is a symbiotic that contains 5 strains of beneficial bacteria to repopulate the gut microbiota and help restore lost functionality of metabolizing fibre into butyrate, a molecular driver of the condition.
In October, American Gastroenterological Association (AGA) released results from the largest trial to date on the effectiveness and safety of faecal microbiota transplantation (FMT). The study enrolled 259 participants receiving FMT in 20 different clinics across the United States and found that 90% of those receiving FMT were cured of C.diff infection within one month.
These treatments will hopefully pave the way for many microbiome based treatments that will help in the battle against aging and age-related disease
Why we think this is revolutionary:
The Targeting aging with metformin (TAME) trial, is the world’s first human clinical trial in which aging will be specifically targeted. Metformin is a drug which has been used to treat type 2 diabetes for the past 62 years. It works by inhibiting glucose production by the liver, resulting in a reduction of blood sugar levels. A long term study in the UK found that people on metformin, even those who were diabetic and obese, had less mortality when compared to control patients without diabetes who were not taking metformin.
The TAME trial, directed by Prof. Nir Barzhali, will be a six year trial involving 3000 participants, between the ages of 65-79 years old. These trials will investigate whether those taking metformin experience delayed development or progression of age-related chronic diseases—such as heart disease, cancer, and dementia.
The impact of widespread metformin supplementation will have a two pronged effect on the life extension of the general public. Metformin is the most widely used drug for treating type 2 diabetes, a disease which reportedly affects a third of the population of developing countries. It is predicted that type 2 diabetes shortens life expectancy by 5-10 years. Not only does it reduce the life expectancy deficit of diabetics back to that of a health control, but it has also been found to possess significant anti-cancer properties, reducing the incidence of some types of cancers from 40-55%.
Why we think this is revolutionary:
mRNA vaccine technology has been around for a while, but it is only recently that we have begun to overcome its drawbacks and see promising results from its use in animals and humans. Our progress came to a head this year with the development of the Pfizer/BioNTech and Moderna COVID-19 vaccines – the former being the first mRNA vaccine to be used in humans outside of human trials.
Unlike conventional vaccines, which usually involve injecting either dead or a weakened form of the virus to stimulate the immune system, the newer technology uses mRNA to instruct cells to make a specific protein or protein fragment belonging to the virus. In this case, the mRNA encodes a harmless piece of the coronavirus spike protein, which the immune system is then primed to attack should the real thing be encountered.
mRNA vaccines avoid the need to culture live viruses as part of development and manufacture, which can drastically reduce costs and, more importantly, time. While the urgency of the pandemic certainly helped accelerate the development of this and other vaccines, the use of the mRNA platform was an important factor that allowed development time to be so drastically cut. Despite the fact that those most at risk from COVID-19 are the elderly and those with chronic conditions, it is still estimated that those who die due to the virus would on average have lived another 10 years or more. For these individuals, the timely delivery of these vaccines will have a significant impact on longevity.
That concludes our roundup of the top 10 developments in health and this year. It wasn’t an easy list to make. Some innovations on this list have immense potential to improve human health and longevity, but were ranked relatively low due to the current uncertainty surrounding their effectiveness. Likewise, estimating the impact on lifespan for many of these innovations was challenging, particularly for technologies that are in an early stage of development. We find it probable that, come 2030, some of our estimations will have been proven wrong, but we are hopeful that most of our picks for this list will lead us further down the path to real improvements in human longevity.
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