[ExI] First hint that body’s ‘biological age’ can be reversed

[John Clark]

This article came from the September 5 2019 New-scientist magazine:
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*Drug cocktail seems to reverse biological signs of ageing in people*

Is this the world’s first anti-ageing drug? Scientists have made people
younger for the first time, or so they think. Nine men took a year-long
drug regime that appeared to reverse the ageing process, leaving them
one-and-a-half years younger – biologically – than when they started.

The clinical trial was the first to investigate the possibility that a drug
might be able to reverse the biological signs of ageing, increasing
lifespan. However, the results are limited by the fact that this was a
feasibility study without a placebo.

The men, aged 51 to 65, took a drug cocktail involving recombinant human
growth hormone (rhGH), three to four times a week for a year. At the
beginning and end of the trial they had their biological age measured.

We all have a chronological age – the number of candles on our birthday
cake – and an epigenetic, or biological age, which is a measure of how
quickly the cells in our body are deteriorating compared with the general
population. These two figures can differ, and our epigenetic age is often a
better predictor of lifespan.

The researchers used four different tests of epigenetic age. On average,
across the four tests, the volunteers’ epigenetic age was 1.5 years younger
than it was at the beginning of the treatment. This means someone who had
an epigenetic age of 55, say, at the beginning of the trial had an
epigenetic age of 53.5 at the end of the year-long trial. The most advanced
test, “GrimAge” – named after the Grim Reaper – showed a 2-year decrease in
epigenetic versus chronological age that persisted six months after the men
stopped taking the drug therapy.

GrimAge determines your epigenetic age by analysing chemical tags that are
added or removed to DNA, which in turn influence which genes are switched
on and off. This is called methylation and changes to this process can be
used to predict your lifespan, as well as your “healthspan” – the time you
have that is disease-free.
Without a placebo, it is difficult to prove that the intervention caused
the anti-ageing effect. However, the team say that despite the small number
of participants, the results would not be expected by chance, and it is
unlikely that lifestyle changes would have contributed significantly to the
outcome. They acknowledge that a placebo effect could have influenced the
results, which they will study in a future trial involving 100 participants.

Spontaneous ageing reversal is intrinsically unlikely, says lead author
Greg Fahy, at 21st Century Medicine in Fontana, California. “If placebo by
itself caused such a strong effect, it would be expected that many prior
interventions would have reported similar effects.”

Fahy points out that his collaborator Steve Hovarth, professor of human
genetics & biostatistics at the University of California in Los Angeles,
has done many studies of diet and exercise in which epigenetic age has been
measured at the beginning and end, and has never observed a 1.5 year
decrease a year later by chance. “Both [diet and exercise] have a benefit,”
says Hovarth, “but the effect is very small. You need thousands of people
to detect it.”

Immune boostThe drug used in the trial aimed at repairing the thymus, a
small organ that plays a key role in the immune system, and which shrinks
with age. Shrinking is associated with poor immune function, and is linked
to an increase occurrence of cancer, infectious disease and auto-immune
conditions. It also leads to an early death. Fahy and his colleagues gave
participants rhGH because studies suggest it can regenerate the thymus.
Extra rhGH can trigger diabetes, however, so they added a supplement called
dehydroepiandrosterone (DHEA) and a drug called metformin, which can
prevent this from occurring. MRI scans taken at the beginning and end of
the trial revealed thymus regeneration, accompanied by improvements in the
immune system, in seven of the participants.

“Perhaps just undergoing this trial somehow changed the behaviour of these
men towards a more healthy lifestyle,” says João Pedro de Magalhães, a
microbiologist, involved in ageing studies at the University of Liverpool.
“Having said that, this study certainly opens exciting avenues for future
work and doing a larger trial with proper controls is now warranted.”

John K Clark
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