AI-Designed Rentosertib Makes Blood Profiles Look Biologically Younger

You cannot alter the age shown on your ID card. But could the age of your body be changed?

New research suggests that a drug developed with artificial intelligence made the blood profiles of people with lung disease appear biologically younger.

The finding was generated by six computer models that estimate biological age by assessing blood proteins. Scientists refer to these models as biological aging clocks.

Although each clock gave distinct estimates according to the treatment dose and phase, all six notably registered a change in the same direction.

Rentosertib and idiopathic pulmonary fibrosis

The drug assessed in the study, published in Nature Biotechnology, is rentosertib.

It was created to treat a disease that causes lung scarring and progressively worsens breathing, while also acting on biological processes connected with aging.

The disease, idiopathic pulmonary fibrosis (IPF), generally affects older people. It is characterised by inflammation, cellular injury and disrupted tissue repair - features that overlap with some changes associated with aging.

This link prompted an important question: might a medicine developed for lung disease also alter biological processes related to aging?

Scientists from Insilico Medicine, Harvard Medical School and other organisations set out to explore this. They revisited blood samples gathered during an earlier clinical trial of rentosertib.

That initial trial included 71 people with IPF. Participants were given one of three rentosertib doses or a placebo. For this new assessment, researchers studied samples from 42 participants, whose average age was 67.

They measured almost 3,000 proteins in the blood. Inflammation, illness, energy metabolism, tissue injury and aging may all leave identifiable signatures in these molecules.

The team then examined these protein patterns with six biological aging clocks. Some models were developed to estimate a person’s age, whereas others were intended to forecast health and mortality risk.

Why six biological aging clocks were used

Why is it significant to use six clocks?

There is no flawless method for measuring biological aging. The result from a single clock might be shaped by the proteins it measures or by how its calculations are constructed.

However, when multiple independently created models identify a comparable shift, the finding is less likely to be merely an oddity of one model.

In this analysis, every one of the six clocks found a move towards a lower predicted biological age in people treated with rentosertib. The placebo group changed very little, while some clocks indicated rising biological age.

The strongest findings appeared at four weeks. In the group taking 60 milligrams once daily, clocks designed to estimate chronological age indicated reductions of between 2.71 and 3.46 years.

Other clocks and dose groups generated different results, including considerably larger estimates from certain exploratory models intended to assess individual organs. Consequently, the researchers did not specify one figure for the total reduction in biological age attributed to rentosertib.

What mattered most was the direction of the effect: despite their different designs, all six clocks detected protein profiles that looked younger in people given the drug.

Rentosertib also changed the levels of 326 proteins, compared with just two in the placebo group. Several were associated with lung scarring and tissue repair. Others had roles in inflammation, energy use, cellular stress and the behaviour of aged or damaged cells.

Many of the protein changes persisted during the 12-week study. Yet the apparent shift towards a younger biological age ceased to grow after week four, instead reaching a plateau.

Limits of the rentosertib findings

Researchers do not yet understand the reason for this. The body may have adjusted to the drug, a different dosing timetable might be required, or the aging clocks may have reached the limit of what they could identify in such a brief study.

The findings are compelling, but they have major limitations.

All participants had serious lung disease. If rentosertib reduced fibrosis or improved their lung condition in another way, that improvement itself could have caused their blood to appear biologically younger.

The clocks may therefore have picked up an improvement in disease, rather than an alteration in aging itself. The study was unable to completely distinguish between these explanations.

The analysis also involved only 42 people and ran for 12 weeks. It did not show that participants had become younger, would stay healthier for longer or would live longer.

It is also important to note that several authors are employed by Insilico Medicine, the company developing rentosertib. Lead author Alex Zhavoronkov is the company’s founder and co-CEO.

At present, rentosertib cannot be called an anti-aging drug. The results must be examined in larger, longer studies, including trials with people who do not have IPF.

Still, six separate clocks indicating the same direction are difficult to dismiss. The research suggests a future in which medicines designed for diseases of old age could do more than address one condition, helping scientists establish whether broader biological processes associated with aging can also be altered.

The study appeared in Nature Biotechnology.

This article was fact-checked and edited by Peter Dockrill. Although we take pride in our process, we are only human. Please let us know if you notice an error.