True Age Measure : Genetics Master Essay

 

It can be said we have two ages: a fixed chronological age based on when we were born and a malleable biological age – the age at which our body is functioning, which can be affected by our lifestyle choices. Dr Morgan Levine designs tools that measure the latter.

In her new book, True Age, she argues that we should regularly measure our own biological age – giving us information we could use to monitor, and even gain control over, our own individual ageing process. 

Levine, 37, is an assistant professor of pathology and epidemiology at Yale University’s school of medicine. This June she will join Altos Labs, a new $3bn (£2.2bn) anti-ageing biotech startup whose funders are said to include Jeff Bezos.

What got you interested in the science of biological ageing?

Growing up with an older father. He was 54 when I was born and people always assumed he was my grandfather. Most kids aren’t pondering their parents’ mortality early on, but I was already consumed with the fear that he might not be around. My mother, who works on ageing policy, also influenced me. I saw the resources it takes to care for older adults and wondered if there was a possibility to delay that need.

Why is biological age important?

It is more informative than chronological age for predicting risk of disease or death. That’s because it is not chronological time that drives the development of disease, but rather the biological changes taking place among the molecules and cells in our bodies.

Most people’s biological age will be within plus or minus five years of their chronological age, but you can have outliers of up to 10 or more years. The wonderful thing, compared with chronological age, is that biological age is modifiable.

We don’t yet know exactly how to modify it to the greatest extent, but the clock can be made to tick slower, or even possibly go backwards, in response to our behaviours (though it can also speed up). The first step is getting a valid and reliable measure of it, which my lab has been working on.

You advocate getting our biological age measured regularly – once or twice a year. Is the science really advanced enough for that?

It is early days for these tests, and they still need improvement. There is no standard, agreed upon way yet for measuring biological age – different methods give different numbers – and there’s probably no “perfect” way either, because there is nothing to compare against.

But they are good enough to give people a general sense of their health status. Both my and others’ labs have shown these measures are better than just the standard cholesterol or glucose level tests that physicians currently use. Doing it regularly gives a more accurate picture: people can put too much weight on a single measurement and things like being sick or uncharacteristically stressed can misconstrue it.

There are various consumer tests available. How might we best measure?

Right now, probably the cheapest and easiest way is based on regular clinical lab tests that people would get done as part of an annual physical. I have published a method of estimating biological age that combines nine blood measures and the calculator to do it is free online.

But there are other ways too. Counting the diseases and/or high-risk conditions a person has and adding this up into a single score is one method, though it is much less predictive for younger people. Molecular-level methods include the measurement of telomere length [the protective sections of DNA at the end of our chromosomes which shorten with age], though I don’t think it is such a powerful predictor.

Another, which my lab has worked on, is epigenetic clocks. These use machine learning to decode some of the patterns of DNA methylation – chemical tags on our DNA throughout our genome that can alter quite dramatically with ageing. Results from our epigenetic measure match with the clinical test because we trained the former on the latter.

You have a vested interest here. You helped develop “Index”, a $499 epigenetic age test which uses a saliva sample and is offered by Elysium Health…

Elysium Health did license [my lab’s] epigenetic measure. I decided to work with them because I wanted to make sure what they provided to consumers was the most valid and reliable version possible. I stopped work with the company last year and I am not receiving any compensation from them (though it was too late to correct for this book).

I’ve never received a dime for the clinical test, which is freely available and I promote equally to the epigenetic test.

Your own biological age is five years younger than your chronological age. But it might not feel so great to discover you are older biologically. Do you understand why people might not want to know?

Completely. It is a personal choice. For me it is just a way to start evaluating things; a potential early wake-up call that could lead to behaviour change. And, because it is potentially modifiable, it is less worrisome than a genetic test, where these are the cards you’re dealt at birth.

Is it just the usual lifestyle factors we all know about but find so hard to implement that can alter biological age?

The patterns we observe are nothing surprising. People who tend to age slower don’t smoke, don’t really drink, exercise regularly, eat lots of plants, get better sleep, and experience less stress. On average, only 10-30% of our lifespan is estimated to be due to genetics.

That means how we age will largely be down to our behaviours – along with some random chance. Something we don’t have control over which has a huge impact is socioeconomic status. Being poor reduces your life expectancy by about 10 years on average, which is on a par with being a current smoker. We think it is chronic stress to some degree.

Caloric restriction (CR) is popular in the tech world as a way of increasing longevity. What evidence is there it works in humans to slow ageing?

The Calerie study [Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy] is really the only randomised clinical trial. Some of the biological age estimates I have created have been applied and they do seem to show some impact from CR, though whether it is down to the restriction of calories or just the lack of overeating, we don’t know.

There is also a question about whether the benefit would be maintained over the long term. Obviously, CR should be at a level where you’re still getting adequate calories. In the Calerie study it was only a 12% reduction. I am not a proponent of CR for most people – there are better ways – but there are probably less health risks with moderate CR versus what is more common, which is overeating.

You and your husband – who also studies ageing – are leaving your current positions at Yale to join Altos Labs, which is focused on turning back the ageing clock through cellular reprogramming. What will you be doing?

One goal is developing biological age measures to a level that they could be a surrogate end point in clinical trials to slow or reverse ageing (using lifespan or disease incidence isn’t really feasible because results can take decades). I’ll also continue to study epigenetic clocks.

They are a bit of a black box. We can estimate ageing epigenetically, but we don’t really understand what is going on.

The mega-rich have a penchant for funding anti-ageing research and Altos Labs seems no exception. Isn’t this just an effort to extend the lives of plutocrats?

That’s not why I joined [Altos Labs]. I would actually have a big problem working on anything that increased health disparities. I joined because I want to keep the majority healthier for longer. Scientists involved in ageing research need to make the case that our involvement is for the greater good.

Wouldn’t anti-ageing research funding be better spent on combating diseases such as cancer, heart disease and so on, which we know are killers?

We look at diseases in a very siloed way, and our medical system goes after one at a time. But the process – biological ageing – that gives rise to cancer is the same one that gives rise to diabetes, Alzheimer’s, heart disease and others. If we can tackle the thing that causes all of them simultaneously, it could deliver a bigger benefit. You would be saving people from, or at least postponing their incidence of, not just one but many major chronic diseases.

At what point does an obsession with staying young and healthy become negative? Shouldn’t wisdom, wrinkles and grey hair be celebrated rather than fought and derided?

I struggle with this. I don’t want to stigmatise ageing. For most people wrinkles and grey hair don’t have a huge effect on quality of life. Delaying biological ageing is about preventing or slowing the accumulation of diseases, which do affect quality of life.

A lot of people in the field want to call ageing a disease. I disagree. Not only does it further stigmatise ageing, but I don’t think we could settle on a chronological or even biological age where you could say: you are diseased now, and you weren’t diseased before.

Is there such a thing as too much exercise?

If you bottled the effect of exercise and sold it as a pill, it would be one of the best anti-ageing interventions on the market. And it is never too late!

But, yes, there is probably a sweet spot for optimal benefits. Past a certain point and there seem to be diminishing returns. It is difficult to know the optimal level and type of exercise for each of us, but likely most of us aren’t even getting close to it.

What do you do to lower your own biological age?

I try to eat a mostly plant-based diet, stay active and exercise. Sleep and stress levels are the areas where I know I need to pay more attention. I do intermittent fasting where I restrict the time window in which I eat. I don’t know if it is CR – I don’t really count my calories – but implementing it isn’t hard.

I always calculate my biological age based on my clinical numbers from my annual physical and I’m due another epigenetic test. But I’m no biohacker: I leave my experimenting to the lab.

Any advice for those who want to go further with biohacking their ageing process to quantify the specific effect of their regimes?

I would caution those interested in self-experimentation not to put too much faith in every single metric. While hypothetically in the future we could have these applications, we aren’t there yet. If anything, I think this kind of testing might dissuade people from unproven interventions: most of the regimes people might test I doubt will show a sustained effect on biological age.

The World Students Society The Guardian.