There are a number of annoying clichés of science reporting, prime among them being the need to make a connection from any research to a specific application. It must be deeply embedded in the journalism culture, or written in a handbook somewhere.
In medicine this means that any study that involves viruses or the immune system’s ability to fight off infection might lead to a cure for the common cold. Any study that has anything to do with cell function might lead to a cure for cancer. Almost any study of the brain might one day cure Alzheimer’s disease.
Add to this – any study that alters a metabolic parameter that changes with age might, of course, reverse the ageing process.
Such were the headlines about a recent study in Cell looking at mitrochondrial function in mice. Here is the summary:
Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD+ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible.
They used the magic word, “reversible” – that means to the media, apparently, the fountain of youth.
The research itself is very interesting. Mitochondria certainly are vitally important to cell function and are implicated in a number of disease processes. The more we learn about the function, regulation, and ageing of mitochondria, the better.
One thing we have certainly learned over the last couple of centuries is that biochemistry and physiology are complex webs of interactions. Our bodies are Rube Goldberg machines, evolved over millions of years to work well enough. Our biology is like code that has been patched, upgraded, and expanded millions of times – it’s a mess.
Another meta-lesson from medical science is that pulling on one thread in the complex biological web rarely has simple or predictable outcomes. If one small change has a clear positive outcome without any downsides, we probably would have evolved that solution long ago. Rather, biological interventions tend to have complex outcomes with many side effects.
What the researchers have found here is one tiny slice of the regulation of mitochondrial function – lower levels of NAD+ with ageing contribute to the decline in mitochondrial function, and artificially raising NAD+ levels restores certain measured aspects of mitochondrial function.
Here is what we do not know – what are the net effects on cell function of prolonged increase in NAD+, what are the net health effects on the organism, are such effects sustained, what are the negative effects?
The researchers, of course, acknowledge this. Reporting on this news item, however, focuses on the potential to “reverse the ageing process” in gushing terms, before finally adding the usual caveats – far enough down that most people probably won’t read that far. The BBC writes:
Experiments showed that boosting NAD levels, by giving mice a chemical which they naturally convert into NAD, could reverse the sands of time.
One week of youth-medication in two-year-old mice meant their muscles became akin to those of a six-month-old in terms of mitochondrial function, muscle wastage, inflammation and insulin resistance.
The words “reverse the sands of time,” or “youth medication” did not appear in the study publication.
The researchers note that the mice did not demonstrate any change with the treatment. Their muscle strength did not increase, despite the reported changes to the muscle cells. In the final paragraph to the BBC article they quote Dr. Ali Tavassoli, from the University of Southampton:
This could be for one of two reasons. Either they need to treat for longer so that the changes occurring in the cells have time to affect the whole organism, or alternatively, the biochemical changes by themselves are not sufficient to reverse the physical changes associated with ageing in the mouse.
More experiments are necessary to see which of these cases are true.
Which do you think is more likely? I certainly hope that increasing NAD+ levels turns out to be an elixir of youth, but I won’t hold my breath. Whenever a study of an intervention fails to find an effect it appears to be obligatory for someone to point out that the lack of effect could be because the dose was too low or the duration of treatment too short. This is, of course, generically true, but doesn’t change the fact that no effect was seen.
Take a look at this headline from The Guardian:
Harvard scientists reverse the ageing process in mice – now for humans.
This article is not about the current research – it is from 2010 and refers to a study in mice involving telomeres. The study looked at mice who lacked the gene for telomerase, which cause premature ageing and organ damage. Some of this damage was reversed when these mice were given injections to reactivate telomerase. Restoring mice to something closer to normal physiology is hardly reversing ageing.
Again, deep in the bowels of the article they discuss the fact that humans are different from mice in important ways regarding telomerase. The enzyme is suppressed as we get older to help prevent cancer from forming and spreading. Reactivating telomerase to reverse aging would likely result in rampant cancer. That is what we call a non-trivial problem.
To be clear, I am not against research into life extension or methods for limiting senescence. These are likely to be useful avenues of medical research. When reporting on such research, however, I would prefer if it were put into a more realistic context.
Ageing is not one process – it is many complex processes. No single intervention is likely to have a significant impact on overall ageing. Interventions are likely to have unwanted consequences, and overall risk-benefit will need to be carefully studied (just like with all medical interventions).
The difference here is that we are not talking about compensating for a dysfunction, but enhancing normal physiological function. This is a much trickier game.
