Biological age reversal seems closer than it’s ever been

“The dreams of youth are fairest,
The dreams of youth are rarest;
The dreams of youth are brighter
Than the dreams we'll know again.
Hope is the fairy weaver
For youth, a firm believer,
And great the things we'll master
In the days when we are men.”

So go the opening lines of the poem The Dreams of Youth by early 20th century British-born American poet Edgar Albert Guest. The sentiments he captures in the stanza are a near-universal expression of not only the dreams of each young generation but also reveal something of the yearning for youth in old age.

Back in the mid-1980s, three young German dreamers, two identical twins and their friend, all teenage boys with a knack for mathematics, physics and philosophy, would meet regularly to discuss these subjects. By 1989, as young adults, the trio made a pact: They would dedicate their careers to the pursuit of science that could prolong healthy human life.

One of them, the friend to the twins, Jörg Zimmerman, went into computer science and artificial intelligence and is now a postdoctoral researcher at the Institute for Computer Science, University of Bonn, and a member of the Artificial Intelligence Foundations Group (AIF). A part of his bio reads: “… and currently I am teaching courses on applying methods from statistics and machine learning to the analysis of biological data.”

One of the twins, Markus Horvath, “fell off the wagon … and became a psychiatrist”, according to his brother, as reported in an article in the peer-reviewed science and technology journal nature.com.

Between 2011 and 2013, the other twin, Steve Horvath, now an age and ageing researcher, geneticist and professor of human genetics and biostatistics, went on to make a ground-breaking discovery known as the Epigenetic Clock, also known as the Horvath Biological Clock, a biochemical test that can measure the biological age of human tissue by studying DNA methylation levels — measuring the accumulation of methyl groups in a person’s DNA.

“You can think of [DNA methylation] as rust in the context of ageing,” explains Hovarth in his March 2020 TEDx talk titled Epigenetic Clocks Help to Find Anti-Aging Treatments.

More than being a gimmick to spot “rust” at cellular level and estimate age, his discovery has been used by him and other scientists to measure how a range of factors affect how quickly we’re ageing at a biological level, as well as how our inherited DNA predetermines our biological ageing.

Some findings are fairly unsurprising, such as one study in which researchers analysed the epigenetic age of blood samples from people who followed various diets and made different lifestyle choices. The results concluded: “Overall, the epigenetic age analysis of blood confirms the conventional wisdom regarding the benefits of eating a high plant diet with lean meats, moderate alcohol consumption, physical activity and education, as well as the health risks of obesity and metabolic syndrome.”

Some findings were more intriguing, such as the role race and ethnicity play in epigenetic age: “In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva and brain tissue.”

Others were downright frightening, such as this one that found that inherited DNA methylation traits can “predict mortality independently of health status, lifestyle factors and known genetic factors”. 

However, in the still-nascent field of age reversal, the accuracy of Horvath’s Clock presents an opportunity for scientists to measure the effectiveness of experiments that seek to reverse ageing at a cellular level. Many of these experiments are covered under an umbrella term known as reprogramming.

“You can take an old cell and administer certain factors… by administering this cocktail of factors for just a few days, not too long. Because, if you administer it for too long, you greatly [increase] the risk of cancer because the cells lose their identity. But if you do it briefly, let’s say for five days, you get the benefit of rejuvenation; you may have rejuvenated the cells by five years or 10 years, but it still remembers its identity,” Horvath explains in a January 2021 video interview.

This cocktail of age-reversing “factors” he refers to are known as the Yamanaka Factors, named after the Japanese stem cell researcher Shinya Yamanaka, who discovered, back in 2006, a way towards reprogramming mature cells back into pluripotent stem cells; that is, immature cells that are able to develop into all types of cells in the body.

Such is the significance of his work that Yamanaka has won numerous science awards every year from 2007 to 2016, including the Nobel Prize in physiology or medicine in 2012. At the time, the Nobel organisation released the following statement: “We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.”

Building on the work done by Yamanaka and many others, in 2013 researchers were able to genetically engineer living mice, so that their cells would revert to an embryonic stage. However, they all developed tumors. Now the work continues to find out if this biological age-reversal can be done without killing the animals.

Recent studies suggest that similar possibilities for age reversal on living humans, sans tumors, might not be far off. In 2019, Horvath was part of a human study that hinted at the possibility that biological age in humans can be reversed. As reported by nature.com, “For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.”

Horvath further explained what the study means for the future in his TEDx talk: “You need to look at it this way; an age reversal of two and a half years means [that] after 12 months … that we stopped ageing, at least in blood tissue.”

Most recently, in a September 2021 article, the MIT Technology Review reported that Horvath was one of a number of leading scientists to join Altos Labs, a new biotechnology anti-ageing company whose reported investors include Russian-born billionaire Yuri Milner and the world’s richest man Jeff Bezos.

The company is just one of a handful of ventures that are betting millions of dollars on beating age and significantly extending human life, largely by conducting research into the nascent field of biological reprogramming technology. As far back as 2013, Google co-founder Larry Page established Calico Labs, a company that states its mission as wanting to “better understand the biology that controls aging and lifespan … and we want to use the knowledge we gain to discover and develop interventions that enable people to live longer and healthier lives.”

Then there’s Life Biosciences, founded in 2017. They have their sights set on ageing itself. And yet another company, Turn Biotechnologies, seeks to reprogramme the epigenome, which is defined as “a multitude of chemical compounds that can tell the genome what to do”.

By any measure, the pursuit of science that could prolong healthy human life, especially the extension of said healthy life towards a century and a half, or possibly two centuries, is still in its nascence. But the work is moving at a relatively fast pace, which in turn holds a revolutionary promise for humanity and the fight against ageing and age-related disease. Admittedly, we have no way of knowing what all the consequences of arguably changing what it means to be human, might be.

At the close of his TEDx talk, Horvath, still seemingly undeterred from that pact he made with his brother and his friend in 1989 when all of them were barely out of their teenage years, tells his 2020 audience: “I’m really happy to say that thousands, if not over 10,000 people, biomedical researchers, are working on various aspects of slowing ageing. And if only one of them succeeds, it will change the world for the better. To the older people in the audience, I want to say, be brave, hang in there. Exciting interventions are in the pipeline.” DM/ML