Forever young: the science of aging well

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“Is aging a disease?”

For a long time, the answer to this question seemed obvious: aging is a natural thing that happens to all of us. It is an inevitable side-effect of growing older. However, with new insights into the processes underlying many chronic diseases and aging, the answer is seeming less clear and researchers are starting to challenge this long-held view.

Tales of the Fountain of Youth have sparked the imagination of mankind for thousands of years, but now it appears as if the dream could become true. Well, at least partially. The aim these days isn’t on eternal life, but rather prolonging our “health spans”: the years of healthy, disease-free living before the effects of old age set in. Who wouldn’t want to live into their late 80s or 90s without any age-related ailments like type 2 diabetes, osteoporosis, or various forms of cancers? Aging and longevity; until recently these were topics that mainly concerned the cosmetic industry and quacks, yet they are now becoming hot topics in the scientific community and biotech industry as well.

Zombie cells

David Sinclair, co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, puts it as such: “The only difference [between aging and disease] in medical textbooks is that: if the majority of people get an age-associated disorder, we call it aging. If less than half of people get something over time: it’s a disease.

While some might be very skeptical and concerned about this ‘attack on aging’, from a scientific and medical point of view it makes a lot of sense.

Disease or not, aging is a highly relevant and independent risk factor for the onset of several chronic diseases in later life-stages. Part of what’s fueling the shifting perception of aging is the identification and characterization of so-called senescent cells. Normally, damaged cells and ill-functioning cells are eliminated by cell death known as apoptosis. However, some cells “zombify” instead of dying, turning into cells that do not proliferate, or fulfil any useful tasks. These senescent cells are persisting in the body and secreting inflammatory compounds which disrupt the functions of healthy cells adjacent to them, thereby contributing to the development of chronic diseases. Studies have shown that the elimination of these senescent cells with “senolytics” (compounds that induces cell death in those zombie cell) not only increase the lifespan but also the health-span of old mice. The process also works in reverse: by injecting a small portion of artificially aged “Methuselah” cells into young mice, you can make the animals slower, weaker and frailer within two weeks’ time.

While some might be very skeptical and concerned about this ‘attack on aging’, from a scientific and medical point of view it makes a lot of sense. It would, for example, be hard to explain why it´s fine to remove precancerous cells, but not senescent cells, from an ailing patient. The difference seems to be purely philosophical.

Miracle pills

Recent long-term studies on type 2 diabetes patients taking metformin (a drug launched in 1957 for the treatment of diabetes) have revealed some very unexpected outcomes. Diabetics taking metformin tend to be healthier, in many ways, compared to diabetics taking other medications: they live longer; have fewer cardiovascular events; and in at least some studies, they were less likely to suffer from dementia and Alzheimer’s Disease. However, the most shocking result was in relation to cancer.: metformin patients seemed to get cancer far less frequently, 25 to 40 percent less often, than diabetics taking two other popular medications. Furthermore, when they did get cancer, they tended to outlive diabetics with cancer who were taking other diabetes drugs. Even more astoundingly, metformin takers did not only outlive diabetic patients taking a different drug, but also outlived the nondiabetic control patients.

Would these drugs be covered by healthcare agencies, or would they create a divide between those who can afford ‘buying’ a longer, healthy life and those that simply can’t?

So far, the FDA and other regulatory agencies do not accept age as a disease, so there will be no clinical trials dedicated to preventing aging anytime soon. Nonetheless, the FDA is willing to allow testing of existing drugs as a prevention against various age-related ailments; a few studies are already underway to test if drugs approved for other indications could be repurposed.

A new age?

Repurposing old, extensively studied drugs might be a low cost and risk endeavor, but as they are already available as cheap generics there is hardly any interest from pharma companies to revive these medications for new indications. Still, there are now several start-up companies focusing on the development of novel ‘anti-aging’ drugs and treatments, which will come with a hefty premium price. The most prominent and secretive company is probably Calico (backed by Googles Alphabet), but there are also many others, with promising names like Human Longevity, Elysium, Unity, Gero, Navitor Pharmaceuticals or Genescient. These companies are trying everything from identifying longevity genes, to selectively targeting potentially beneficial pathways, administering stem cells and even infusing people with ‘young’ blood.

To read more about curing all the world’s diseases, read this previous V-Bio article

There are still many open questions left unanswered: Do we all want to ‘pop a pill’ every day protect ourselves from aging? Would such a pill actually have the opposite effect on the health of many people, by encouraging them to skip healthy habits (counting on the drug to do the job)? Would it lead to a reduction in healthcare costs, or would the costs explode? Would these drugs be covered by healthcare agencies, or would they create a divide between those who can afford ‘buying’ a longer, healthy life and those that simply can’t? How would we determine who should take which of these miracle drugs and can the planet bear even more healthy, active, consuming humans?

One thing is for sure: it will be a (life)long experiment, but the studies have already begun. The launch of every new “anti-aging” company indicates that VCs are starting to believe that this concept is more than just a wild dream. Only time will tell if this is indeed the dawning of a new age.