Do We Finally Have an Anti-Ageing Drug? No, It's Not That Simple

At the outset, the study had a lot going for it: Harvard scientists, paper published in a fancy journal, etc. But most coverage ignored two key issues with it.

As we age, our cells start to lose their ability to repair mistakes in their DNA. That’s why older people’s DNA is more prone to damage, making them more prone to diseases like cancer. Recently, scientists at Harvard Medical School showed that it is possible to stop this aspect of ageing. When the elderly subjects of their experiment were fed with water containing a specific molecule, their cells became more resistant to DNA damage – just like when they were younger. This study was published in one of the more reputed scientific journals in the world, Science, on March 24, 2017. So have we finally found our anti-ageing drug?

It’s not that simple.

L. Aravind, an evolutionary biologist at the US National Centre for Biotechnology Information, is one of the authors of the paper. In an email interview, he confirmed that this discovery, at its core, is a biochemical one. It deals with three proteins found in most of our cells: NAD, DBC1 and PARP1. Of these, NAD is a central molecule that is most familiar to us. It is a critical ingredient in hundreds of reactions that keep the cell running. Without NAD, a cell cannot survive.

The PARP1 protein is important because it raises an alarm when the DNA in a cell has been damaged. The cell’s machinery is then triggered to correct this DNA. And DBC1 is a protein that is abundant in cells but the details of its role are a mystery. The researchers now discovered that DBC1 likes to attach itself to PARP1. But this is a problem because a PARP1 stuck to a DBC1 can no longer act as an alarm. That’s bad news for the cell because if its DNA somehow gets damaged, it is then less likely to repair itself.

So is this the end for the cell? No. The team also discovered that NAD can come to the rescue. It turns out that DBC1 also likes to attach to NAD. And DBC1 cannot go stick to a PARP1 anymore if it is already stuck to a NAD. This leaves the PARP1 free to conduct DNA damage correction. In fact, NAD is so dynamic that it even has the power to free a PARP1 from the clutches of a DBC1.

This all implies that the more NAD our cells contain, the more hardy – and capable of correcting DNA damage – our cells are. Older cells have less NAD and so are less hardy than younger cells. This is why these scientists propose that replenishing our cells with NAD “can be used as a means of reducing the side effects of chemotherapy, protecting against radiation exposure, and slowing the natural decline in DNA repair capacity during ageing.”

As an evolutionary biologist, Aravind explored a more fundamental question that this discovery threw up: “Why should such a paradoxical mechanism exist in the first place?”

“PARP1s are major NAD consumers – in a typical run, they can consume several hundred NAD molecules,” he said in an email, pointing out that since NAD is such a central molecule in running the cell, we don’t want PARP1 to run away with all of it unless there is a real danger to the cell. This is why we need DBC1. “It is critical to have a sensor that allows the PARPs to be unleashed only if the concentrations of NAD are high enough to allow this luxury. DBC1 is that sensor. Given that NAD levels decrease with age, this luxury diminishes and thereby [affects] DNA repair.” He summed up this: “Supplementation by NAD precursors might offset some of the issues associated with ageing.”

At the outset, the study has a lot going for it: Harvard scientists, interest from NASA (the research won a NASA competition for its lifesaving potential during space exploration) and a paper in Science. And it did not take long for the media to latch on to the sensational implications of this research. Soon enough, there came headlines like ‘Is this pink pill the elixir of youth?’, ‘Anti-cancer ‘youth pill’ available in three years’, ‘Discovery could reverse ageing and help us live on Mars’, ‘New wonder pill to reverse effects of ageing’ and even ‘Revolutionary anti-ageing drug makes you look younger and live longer’. All of these statements have some basis in truth but none have laid enough emphasis on two key points.

Point 1: The study was done in mice

To get started on testing their hypothesis that NAD could bolster DNA repair, the scientists used mice. It worked. Old mice, even when they were subjected to radiation (which mutates DNA), had their DNA-repair powers boosted to the levels of young mice when fed with an NAD precursor. But something that works in mice need not work in humans. With this in mind, David Sinclair, the lead author of this paper, has announced in a press release that human trials will begin in a hospital in six months and that if all goes well, we could have an NAD-based drug hit the markets in three to five years.

This is hugely optimistic because, as popular as mice are as model organisms for such studies, they come with serious caveats. Radhika Nair, a cancer biologist at the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, told The Wire, “Unfortunately, translating mouse models into actual human trials is a long, expensive process and fraught with failure. This can be attributed to a number reasons such as the differences in mouse and human physiology, the set-up of clinical trials, etc.” She was not involved with the study.

The problem of translating basic research into clinical applications is so severe that a Nature feature in 2008 termed this gap ‘the valley of death’. Aravind, who worked with Sinclair and team on this study, agrees that this bit of research will also have to cross several hurdles before being useful to human beings. “What works well in smaller animals like mice might not scale in large ones like humans. Importantly, the difference in terms of lifespan means the time of initiating treatment in terms of human age needs much more study.”

Point 2: The lead scientist has a commercial interest in this research

David A. Sinclair is a biologist at the Harvard Medical School and a prominent figure in the study of ageing. His lab has come up with significant discoveries in the area before, many of which have also been published in reputed journals and widely publicised. However, all of the papers are careful to disclose this fact “D.A.S. is an unpaid consultant, board member, inventor on patent applications, and holds equity in companies developing NAD precursor–based medicines”.

There is nothing particularly fishy about this. It is quite common for scientists to also be entrepreneurs; some even believe that commercialisation is necessary for promising molecules to be translated quickly into clinically useful products. Nevertheless, it’s important to realise that when a scientist behind a discovery has a company that is looking to cash in on it, it means that he or she has a lot to gain by any hype resulting from the discovery.

It is thus common to see many of these scientist-entrepreneurs go out of their way to make their research accessible to their future customers: the layperson. Sinclair, for example, is a popular face, having given a TEDx Talk, made animations and given plenty of interviews. The unfortunate side-effect of this is that many journalists get lazy when all this information is made readily available for them. There is a temptation to take the information fed to them at face value and that’s how we get sensational reports like the headlines mentioned earlier. Sinclair could not be reached for comments on the media’s coverage of his research.

This is still an important study

None of this is to say that this study is not a significant one. Indeed, it does seem to be, and there are also other scientists involved in the research like L. Aravind who have no commercial interests in it. “I am personally for all research relating to any aspect of human health not being used as an instrument of monetisation,” he clarified. “As an employee of the US government, at least the part my group plays in such research is made entirely publicly available for anyone to use and I don’t gain monetarily from such findings.”

Aravind pointed out that claims of miracle cures have cropped up throughout history, each time disguised as a breakthrough. “Hence, skepticism in this regard is entirely warranted, given that though we understand much more now than 1,000 years ago, we still don’t know a whole lot,” he said. “It is important that the media communicate the logic behind the biochemistry and what these studies are contributing to the understanding of workings of our bodies than trying to sell the hope of the latest elixir.”