There’s been a lot of talk lately about possibilities for treating aging—from blood transfusions from old mice to young, to eradicating “zombie” cells, to taking daily rapamycin and metformin pills to extend your healthspan. Some of it sounds like science fiction; some of it is. But what is very real is what is underlying all the talk: the creation of a very substantial new field of science, and a new area of biology, focused on the aging process.
Aging doesn’t kill people—diseases kill people. Right? In today’s world, and in a country like the United States, most people die of diseases such as heart attack and stroke, cancer, and Alzheimer’s. These diseases tend to be complex, challenging, difficult, and extremely ugly to experience. And they are by nature chronic, caused by multifactorial triggers and predispositions and lifestyle choices.
What we are only now beginning to understand is that the diseases that ultimately kill us are inseparable from the aging process itself. Aging is the root cause.
What we are only now beginning to understand is that the diseases that ultimately kill us are inseparable from the aging process itself. Aging is the root cause. This means that studying these diseases without taking aging into account could be dangerously misleading… and worst of all, impede real progress.
Take Alzheimer’s disease. To truly treat a disease like Alzheimer’s, we would need to identify and understand the biological targets and mechanisms that trigger the beginning of the disease, allowing us to intervene early—ideally, long before the onset of disease, to prevent any symptoms from happening. But in the case of diseases like Alzheimer’s, the huge problem is that we actually understand very little about those early targets and mechanisms. The biology underlying such diseases is incredibly complex. We aren’t sure what the cause is, we know for sure there isn’t only one target to hit, and all prior attempts to hit any targets at all have failed. When you start to think about how much of what we think we know about Alzheimer’s comes from very broken models—for example, mice, which don’t get Alzheimer’s naturally, so how could you test drugs for it on them?—it becomes totally obvious why we’re at a scientific stalemate in developing treatments for the disease, and that we’ve likely been coming at this from the wrong direction entirely.
The biggest risk factor for Alzheimer’s isn’t your APOE status; it’s your age. People in their twenties don’t get Alzheimer’s. But after you hit the age of 65, your risk of Alzheimer’s doubles every five years, with your risk reaching nearly one out of three by the time you’re 85.
What if going after this one biggest risk factor is the best vector of attack? Maybe even the only way to truly address it? This isn’t about the vanity of staying younger, about holding on to your good looks or your ability to run an 8 minute mile. It’s about the only concrete possibility we have to cure these diseases. Instead of choosing targets for a single specific disease, i.e. a specific condition that arises in conjunction with aging, we can get out in front of disease by choosing targets that promote health. And we can identify these by looking at disease through the lens of the biology of aging.
Take the example of senescent cells. These “zombie” cells that accumulate with aging were long postulated to be actively toxic. In 2016 scientists discovered that simply deleting these cells in middle-aged mice could dramatically increase lifespan and delay the onset of age-related disease. While the first clinical skirmish against this toxic cell type was not successful (for a particular target, and a particular indication, osteoarthritis), today there is a whole new crop of biotech companies actively targeting this cell population with different small molecules addressing multiple different biological pathways, and planning human clinical trials in a broad range of different indications: Alzheimer’s, COPD, macular degeneration, frailty… the list goes on. The one common risk factor underlying all these different diseases? Aging.
Looking at aging will be our compass to the medicines of the future.
Looking at aging will be our compass to the medicines of the future.
The study of aging itself is a tantalizing and magical one—conjuring images of a fountain of youth. And there is much evidence to show that such a broad vision might actually be within reach, one day; that we could stop cell death, that we could slow down or even reverse our internal molecular clocks. But in a way, the study of aging is a trojan horse, gaining us access to a much more concrete, immediate new world of possibility. Our next, best set of targets for the therapeutics of the future will come from aging biology—therapeutics for diseases that have a massive unmet need, and that many of us are suffering from right now.
So what will that future look like, developing a new drug that treats so many different disease mechanisms? What does a longevity therapeutic even look like? If we think of this new field of aging and longevity as following the path of drug development from other new fields of biology, individual small molecules and biologics that hit specific factors will be the low hanging fruit that is tested in the clinic first. In time, newer and more precise modalities may better target the molecular factors that cause aging. And because aging is multifactorial and driven by multiple independent pathways and mechanisms, ultimately a combinatorial strategy of hitting multiple pathways simultaneously will have the highest impact.
Even with our best efforts, best technologies, and best science for each of these major diseases, curing age related diseases one at a time is ultimately low impact. Let’s say we completely cured cancer; that would add a paltry 4yrs to average lifespan, because another major killer like stroke would be just around the corner. Only by targeting aging itself can we make significant impact on improving quality of life and healthspan.
Understanding how we age is a way into a new era of medicine, into identifying new targets for diseases we’ve never truly understood (let alone known how to treat).
The cure for aging just might be the cure for disease.
