Originally posted on Medium on May 11, 2022.
Extending healthy lifespan of mice by 36%, reprogramming old cells into young cells and regenerating lost frog legs with bioelectricity. These are some impressive results from longevity science and regenerative medicine from the last few years. Technologies like these could one day significantly increase human health and lifespan and improve the quality of life for billions. More awareness of these developments, and less confusion about the ethics involved, could speed up progress.
We have seen a dramatic increase in global human life expectancy in the last hundred and fifty years: from 30 years around 1850 to almost 80 years today. This period of improvement, called the ‘health transition’ by epidemiologists, was caused by better sanitation, nutrition, hygiene, and medical science. The top causes of death also changed. While people in the past mainly died from infectious diseases like influenza and pneumonia, tuberculosis, and gastrointestinal infections, today the top killers are chronic diseases like heart disease, stroke, cancer, and diabetes. Interestingly, the chance of dying from one of the modern diseases increases exponentially with age.
Why is that? Why does our health deteriorate when we get older? Although we still don’t know exactly what aging is, a key aspect seems to be an accumulation of damage in the body. This is damage on a molecular and cellular level and includes the loss of genetic information, decreased protein regulation, disrupted cellular communication, stem cell exhaustion and an increase of dysfunctional called ‘senescent’ cells. Young bodies can often repair themselves, but the older you get, the harder this becomes. Eventually the damage builds up, leads to chronic illness and, finally, death.
So far, the most effective method to delay this process is a healthy lifestyle. With eating healthy and in moderation, regular exercise, not smoking and not drinking too much alcohol, you can get up to ten extra years in good health. Having the right genes also helps. About 25% of the variation in human longevity seems to be due to genetic factors. But even with the healthiest lifestyle and genes in the world, there comes a time when your body breaks down and chronic illness appears.
Our medical approach until now has been to deal with each illness in isolation. The problem here is that, even if we manage to halt or slow down one chronic disease, the patient often falls prey to the next one. Their accumulated damage affects their entire body in the end. Disease treatment in the elderly becomes like a game of Whack-A-Mole.
Longevity science, also known as geroscience, approaches the problem from a different angle. It tries to maintain health and prevent disease by intervening in the molecular and cellular causes of aging and helping the body to repair itself early on. This way, it produces results faster than conventional medicine and by targeting the aging process itself, all age-related diseases are dealt with at the same time. Sounds too good to be true? Let’s look at some recent animal studies from this field.
In a study in 2018, researchers from the Mayo Clinic in the US eliminated senescent cells in old mice with certain drugs called ‘synolytics’. As mentioned earlier, senescent cells are dysfunctional. They stopped dividing and release chemicals that can trigger inflammation, but they do not die (they are also called ‘zombie cells’). Initially these cells are cleared by the body’s immune system, but, as an organism ages, this process becomes less effective, causing these cells to damage surrounding tissues. In the study, 2-year-old mice (equivalent to about 70-year-old humans), were given two drugs for over 4 months that kill senescent cells: Dasatinib (an anti-cancer drug) and Quercetin (a plant pigment found in some foods). The result was that these mice stayed healthy longer, walked faster, had better endurance, and eventually lived 36% longer than the untreated mice.
In another study done at Harvard in 2020, researchers led by geneticist David Sinclair were able to rejuvenate eye cells in mice with a technique called ‘cellular reprogramming’. Earlier it was discovered that a cell can be converted back to a stem cell, which in turn can grow into any type of body cell, by activating certain genes called Yamanaka factors. But reprogramming can also be done partly, resetting the cell not all the way back to its stem cell stage (where it has lost its identity), but to a younger version of itself. Sinclair’s group used partial reprogramming on damaged eye cells of blind mice (due to glaucoma or aging), finding that their optic nerves regenerated, and that the mice ultimately could see again.
Results like these have not gone unnoticed outside academia. For instance, Altos Labs, a biotech company started in 2022, will be focusing on reprogramming and received a whopping $3 billion in funding from investors like Amazon’s Jeff Bezos. And they are not the only ones.
Another promising technology comes from the field of bioelectricity. It turns out not only nerve or muscle cells communicate with each other electrically, but all groups of cells do. These electrical signals seem to play a crucial role for building body parts in an organism like eyes, hearts, and legs. Biologist Michael Levin and his colleagues at Tufts University in Boston have been trying to decode these signals the last few years. They also tried to manipulate them with ion channel drugs and others, and this was not without success. They managed to create flat worms with multiple heads and tadpoles with an extra functional eye on their back or their tail. More practically, earlier this year they were able to largely regrow the amputated leg of an adult frog, something that does not naturally happen. They are now testing limb regeneration on mice.
Similar research has been done in labs around the world on yeast, fruit flies, zebrafish, and other organisms. Mind you, as promising as some animal experiments are, there is no guarantee that the studied techniques will also work in humans. And even if they would, first they must go through a long period of testing and clinical trials before they will be available as regular therapies. But exploring this avenue further is highly worth it, for multiple reasons.
First, technologies like these could stave off age-related decline and significantly improve our quality of life. Normally, what awaits us later in life is not only gray hair and wrinkles, but also hearing loss, deteriorated eyesight, weaker muscles, back and joint pain, reduced fertility, diminished memory… the list is long. And when one of the dreaded chronic diseases sets in, our final years are often tainted by chronic pain, fatigue, and depression. To put a number on this, in 2019 The Global Burden of Disease Project calculated the number of lost healthy years in the world due to premature death or disability at 2.5 billion, and half of these lost years are thought to be caused by age-related disease.
Also, the economic case for healthy aging is compelling. People everywhere are getting older than before: it is estimated that between 2015 and 2050, the proportion of the world’s population over 60 years will nearly double from 12% to 22%. Most of these people will eventually get ill, leading to enormous healthcare expenditures. In a recent study it was estimated that increasing healthy life expectancy by just one year could be worth trillions of dollars in the US alone.
Surprisingly, not everyone seems to be in favor of extending healthy life. Misunderstanding might be a factor here. Some are for instance under the impression that geroscientists are trying to extend the part of life when we’re already weak, frail, and sick. This wouldn’t make much sense. The goal always is to extend the healthy part of life, also called healthspan, and postpone sickness as much as possible.
Another popular objection to longer lives is the danger of overpopulation, considering its effects on resource depletion and the climate. But this might be less of a problem than you think. Since the 1970s, growth of the world’s population has been slowing down, and it’s estimated to stop in 2100, stabilizing the number of humans at 11 billion. In many European countries and Japan, the population is even already declining. The main explanation for this is that the fertility rate has been decreasing. Less poverty and improved health conditions are causing people to have fewer children than before because more survive their vulnerable childhood. Also, the position of women has much improved, making them stay longer in school, marry later, and have children later. Of course, a longer lifespan could eventually still lead to a larger population, but this will take decades. In the meantime, technology (energy, agriculture, transportation, space etc.) will progress and could very well provide us with new solutions. And wouldn’t any alternative be better than allowing people to get sick and die?
Then there are those who believe life-extension is somehow unnatural, or not something they want for themselves. Here an interesting question is, what exactly is ‘natural’? In the animal kingdom you will find an impressive range in lifespan: from the 1-day Mayfly to 250-year-old Greenland Sharks. Some species of jellyfish are even immortal. And would longevity technology be any less natural than existing medicine? Most of our treatments so far have been efforts to counter what otherwise would happen ‘naturally’, namely getting sick and possibly dying. Finally, those who don’t want medicine for themselves (longevity-related or not) can of course simply not take them.
People might also fear that longevity technology will only be for the rich. Initially this could be the case. Many technologies like cars, computers and smartphones were first only available to the happy few. But it didn’t take long for them to become widespread. Furthermore, economic forces are expected to drive longevity-tech prices down quickly, like the enormous market size (almost all humans on earth) and subsidies from governments and insurance companies who have an obvious interest in saving on healthcare costs. The Covid-19 pandemic demonstrated what’s possible if we put our minds to it: more than half of the world was provided with important medicines in just two years. Admittedly, rich countries got them first, but poor countries are catching up quickly.
Finally, some could have concerns about the ethics of biomedical research in general. Techniques like genetic engineering and synthetic biology can conjure up images of designer babies, super soldiers, and other dystopian ‘Brave New World’-like developments. Others might have religious motivated reservations. Granted, we must be extra careful with biomedical research. We must firmly protect research subjects, be on the lookout for unwanted side-effects, and minimize the suffering of lab animals. But we should also keep an open mind to the huge potential benefits of these technologies. Remember that many treatments that were once considered dangerous, even obscene, like vaccination, blood transfusion, artificial insemination, and organ transplantation, later turned out to be of tremendous value to healthcare and wellbeing.
Today, we see tantalizing hints on the horizon of technologies that could extend human health- and lifespan. It might even be the dawn of a next ‘health transition’. To make this happen, we need more research into the basic biological processes of aging. International investments in geroscience haven been on the rise the last few years, which is great, but funding is still less than that spent on research into individual diseases like cancer. One of the reasons for this, is that aging is not recognized as a disease itself, making it more difficult to get research grants or expect reimbursement for future treatments by healthcare insurance. More awareness of healthy aging possibilities and their potential, and less concern about their ethical implications, could improve things. It would also speed up the technological progress, which is of the essence. Every year, millions of people get sick from chronic diseases and die, so the sooner we can alleviate some of this suffering, the better. And wouldn’t it be great if we could already enjoy a longer healthy life ourselves?
Some books on longevity science
- Ageless: The New Science of Getting Older Without Getting Old by Andrew Steele (2020)
- Lifespan: Why We Age – and Why We Don’t Have To by David Sinclair (2019)
- Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime by Aubrey de Grey (2007)
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