When we talk about curing ageing, it is tempting to imagine that there is one obvious objective, which is to find a way to stop the human body from deteriorating and therefore allow people to remain healthy for much longer than they do today. There are two different ways of approaching that goal, one approach is to repair the damage that ageing causes, while the other is to alter the underlying biological processes that cause ageing in the first place.
The longevity scientist Aubrey de Grey's philosophy is built around the idea that ageing can be understood, at least in large part, as an accumulation of molecular and cellular damage. Rather than attempting to prevent every biochemical process that produces this damage, he proposes developing therapies that can periodically repair or remove it, and the important point here is that the objective is not simply to treat the diseases that tend to appear in old age, but instead to intervene earlier and repair the underlying cellular and molecular problems before they eventually develop into disease.
He divides ageing damage into several broad categories, including the loss of cells, the accumulation of senescent cells, mitochondrial mutations, intracellular and extracellular waste and structural changes such as extracellular crosslinking. The proposed solutions therefore include regenerative medicine, gene therapies, molecular waste removal and the elimination of senescent cells, among other approaches. This is a serious and intellectually appealing way of thinking about ageing because, if an ageing body accumulates damage over time, it seems reasonable to ask why we should not simply find ways to remove that damage and restore the body to a more functional state. A classic car provides a useful analogy for understanding the idea.
Imagine a classic car that is kept in exceptionally good working order for several decades, and as its tyres gradually wear out, they are replaced, while its brakes are renewed when they begin to deteriorate and, eventually, components of the engine are replaced as they become worn out. The suspension can also be renewed, the electrical system can be repaired when faults develop, and the bodywork can be restored when it begins to corrode. If this process of maintenance is sufficiently effective, then there is no obvious reason, at least in principle, why a sufficiently well-maintained car could not remain functional for an extraordinarily long period of time.
De Grey explicitly makes use of this kind of engineering-maintenance analogy, because his argument is essentially that the human body could similarly be maintained by repairing the damage that normal metabolism inevitably produces over time. There is something quite compelling about this idea because we do not necessarily need to understand every single detail of why a car ages in order to keep repairing it; instead, we need to understand what has gone wrong, identify the component that has failed or deteriorated, and then develop a reliable way of fixing or replacing it. If that principle can be successfully transferred from engineering to biology, then perhaps we could maintain a human body in much the same way.
However, this is where I have a philosophical reservation, because even if we eventually develop extraordinarily sophisticated rejuvenation medicine, there remains an important question about what exactly we would mean by having "cured" ageing. Suppose, for example, that at the age of 60 you undergo a treatment that restores your tissues to something resembling their condition when you were 40, and as a result you remain healthy for another 20 years. At 80, the damage has accumulated again, and so you undergo another treatment, while at 100 you require another, and then at 120 you require another after that.
Such a development would unquestionably represent an astonishing medical achievement, because it could allow people to remain healthy for vastly longer than they do today. Nevertheless, we would still have to ask whether we had actually cured ageing, or whether we had simply become exceptionally good at maintaining an ageing organism. To me, that distinction is important, because there is a conceptual difference between stopping a biological process and repeatedly repairing the consequences produced by that process.
A facelift provides a relatively simple illustration of this distinction. A facelift can make an ageing face look considerably younger, and although the result can be dramatic, the underlying biological processes of ageing continue regardless. Eventually, therefore, another facelift might be required, and nobody would normally describe the original facelift as having cured ageing. It has altered one of the visible consequences of ageing, but it has not fundamentally changed the process that produced that consequence.
Likewise, imagine a future in which we could repeatedly restore an elderly person's tissues to a youthful state, perhaps even making an 80-year-old function biologically more like a 40-year-old. That would certainly be revolutionary medicine, and it could potentially transform the human experience of old age, but if the underlying biological ageing process continued beneath the treatment and continued producing the same forms of damage, then I would still describe this as a form of age management. It would be extraordinarily sophisticated and effective age management, but it would nevertheless still be age management.
This is where the classic-car analogy becomes particularly interesting, because de Grey's answer is essentially that it does not necessarily matter whether the car's components would naturally deteriorate if we become sufficiently good at replacing them. If the car can remain permanently functional because we are capable of continually repairing whatever goes wrong, then from a practical perspective we have effectively defeated the consequences of ageing, even if we have not eliminated every underlying reason why individual components would otherwise deteriorate. I think that is a perfectly reasonable definition of success, and indeed, from a practical medical perspective, it might be the definition that matters most. However, there is another way of looking at the same car, and that is to ask whether we could eventually discover why every component was wearing out in the first place.
Suppose that, rather than continually replacing the car's parts, we discovered how to alter the underlying mechanisms that caused those parts to deteriorate. Imagine that we could change the engine so that it no longer gradually wore out, alter the suspension so that it no longer degraded, prevent the electrical system from accumulating faults, and protect the bodywork from corroding. In that situation, we would no longer merely have become exceptionally good at repairing an old car; instead, we would have fundamentally changed the ageing process of the car itself.
That, to me, is a fundamentally different achievement, and it is a distinction that I think can become lost when the term "anti-ageing" is used too broadly. If we use the same phrase to describe everything from slowing biological deterioration to periodically repairing accumulated damage and, ultimately, completely preventing the biological processes associated with ageing, then we risk treating very different achievements as though they were essentially the same thing.
There is actually a third approach as well, because rather than repairing damage after it has appeared, we can attempt to slow the rate at which that damage accumulates in the first place. This is where many of the interventions being investigated within geroscience sit, because exercise, nutrition and various pharmacological interventions might influence processes such as metabolism, nutrient sensing, inflammation, mitochondrial function, autophagy and other biological mechanisms that are associated with ageing.
The drug Rapamycin is particularly interesting in this context because it targets mTOR, which is a major nutrient and growth-sensing pathway, and its effects have made it one of the more extensively studied pharmacological approaches to slowing certain aspects of ageing. However, even here, there is an important conceptual distinction, because slowing ageing is not necessarily the same thing as stopping ageing. If a drug reduces the rate at which biological deterioration occurs by 20%, for example, that could still be enormously valuable if it means that a person remains healthy for several additional years. Nevertheless, the underlying ageing process would still be operating, albeit at a slower rate.
This is why I find the distinction between slowing, repairing and stopping ageing so useful, because it allows us to separate several different goals that are sometimes grouped together under the same general term. Slowing ageing means that damage accumulates more slowly, while repairing ageing means that accumulated damage is periodically removed or corrected, and stopping ageing would mean that the underlying processes responsible for progressive biological deterioration had been fundamentally altered. Reversing ageing would then take the idea one step further, because it would involve restoring an already old organism to a younger biological state and then somehow allowing it to remain in that state rather than simply beginning the ageing process again.
None of this means that the “repair-and-repeat” approach should be dismissed, because far from being something I would consider undesirable, it could represent one of the greatest achievements in the history of medicine. If I could choose between ageing normally and having access to periodic treatments that restored my biological condition to that of a much younger person, I would choose the latter. A treatment that allowed an 80-year-old (I am not 80, by the way!) to function more like a healthy 50-year-old would be an extraordinary achievement, even if that treatment had to be repeated throughout the person's life, and de Grey's concept of “longevity escape velocity” makes the argument considerably more ambitious still.
The basic idea behind longevity escape velocity is that the first generation of rejuvenation therapies does not necessarily have to solve every form of ageing damage once and for all. Instead, those therapies would only need to provide enough additional healthy life for subsequent generations of technology to be developed, and those improved therapies could then provide additional time for still better therapies to emerge. In this way, each generation of medicine could potentially extend healthy life sufficiently for the next generation of medicine to arrive before the damage of ageing once again became overwhelming.
Under that scenario, medicine could theoretically remain ahead of ageing indefinitely, and the person would therefore not necessarily receive exactly the same treatment every few years forever because the treatments themselves would continue to improve. First-generation rejuvenation might repair some forms of damage, while second-generation therapies could repair a broader range of problems, and third-generation therapies might become considerably more precise, effective and safer. Eventually, the cumulative effect of these improvements could potentially result in indefinite healthy life, which is an extremely interesting possibility even if it does not quite amount to what I would personally call a cure for the ageing process itself.
For me, a genuine cure for ageing would require something more fundamental. Imagine, for example, that at the age of 60 a person undergoes an intervention that restores their biological state to approximately that of a 40-year-old, but instead of simply allowing the same ageing processes to begin again, the intervention has fundamentally altered whatever mechanisms are responsible for progressive biological deterioration. In that situation, the person could remain biologically around 40 even as their chronological age continued to increase, so that at 70 they were still biologically 40, at 80 they were still biologically 40, and even at 100 or 120 they remained approximately at that same biological state.
Such a person might still eventually die from an accident, an infection, cancer or some other disease, because preventing ageing would not necessarily make someone completely invulnerable to every possible cause of death. However, they would no longer be undergoing the progressive biological deterioration that we currently call ageing, and therefore I think such an intervention would genuinely deserve to be described as a cure. It would no longer be a matter of continually putting a plaster over the consequences of ageing; instead, it would be more like removing the mechanism that keeps producing the wound. There is also no reason to think that these different approaches are mutually exclusive, because the eventual longevity toolbox could contain several different layers that work alongside one another.
