Question of the Month #15: Would Other Rejuvenation Biotechnologies Keep Us Cancer-Free?

Q: SENSRF has backed a bold, long-term strategy to eliminate cancer. But cancer is very rare in young and early middle-aged adults. Might keeping the body young with other rejuvenation biotechnologies be enough to hold cancer at bay without the need for more intensive, specific approaches?

A: It’s certainly a good bet that applying rejuvenation biotechnologies to remove, repair, and replace other kinds of aging damage will in some ways make us less vulnerable to cancer. Notably, ablating senescent cells would eliminate the “senescence-associated secretory phenotype” (SASP), which promotes the growth and invasiveness of cancers in several ways, including stimulating early-stage cancer cells to continue replicating, encouraging the growth of new blood vessels needed by cancer cells to supply themselves with fuel and oxygen, and breaking down the physical barriers that prevent them from metastasizing, which is when most cancers become deadly. Also, rejuvenating the aging immune system (by eliminating the dysfunctional T-cells that accumulate with age and rebuilding the atrophied thymus gland) will restore the body’s ability to suss out and eliminate cancers as they emerge.

But it’s also clear that deploying these other rejuvenation biotechnologies won’t be enough to eliminate cancer altogether, and that must be our ultimate goal.

First, we already know that cancers can evolve multiple mechanisms to avoid being hit or destroyed by antibodies and immunological factors targeting “cells with antigen X,” and the longer a person lives with proto-cancerous cells (even in the presence of a healthy, young immune system), the longer those cells have to develop ways to evade such an immune system. This is one of the reasons that cancer is an age-related disease, despite the fact that young people can and do certainly get cancer, and despite the fact that many late-life cancers originate with mutations that arise in the body decades earlier.

More importantly, perhaps, there is good reason to worry that otherwise-rejuvenated tissues in a body that is still vulnerable to the core processes of cancer may actually become more vulnerable to cancer than they would be under “aging as usual.” Consider the following contrasting scientific findings.

On the one hand, it has been shown in animal experiments that when you transplant a pre-formed cancer into an old host, it usually grows more quickly than the same cancer does when transplanted into a young one.¹ This is as you’d expect from things that make the aged host more vulnerable to cancer: senescent cells make it easier for the implanted cancer to take root and spread, and a flagging immune system is less able to root out the invader.

On the other hand, when you infect mice with a virus that can cause new cancers to form, it is actually less likely to happen in an old mouse than in a young one — and the tumors that do form grow more slowly,² despite the weakened immune system and burden of senescent cells in the older animal. This strongly suggests that something about biological aging itself eventually makes our tissues less prone to forming cancers.

Consistent with this, consider the phenomenon of people (and mice) with mutations in DNA repair genes that cause them to accumulate mutations more rapidly than the rest of us. These people develop an “old” burden of potentially cancer-causing mutations in a body that is otherwise still young. This would be similar to having an otherwise-rejuvenated body in which the problem of age-associated mutations had not been solved by a specific rejuvenation biotechnology. As is well-known from cases like the BRCA1 mutations borne by Angelina Jolie, such people develop what are often very aggressive cancers at much younger ages than is typical in the general population. This suggests that once the mutations needed to form a cancer take hold, even an otherwise-young body is unable to hold the invasion back.

There are also ways in which older bodies may actually be more resistant to the growth and spread of cancer than young bodies. As we age, the cells needed to make the extra blood vessels required by cancer cells to maintain the supply of oxygen and nutrients they need to fuel their furious growth either run out of replicative steam or are lost altogether. As well, levels of the hormones, cytokines, and other growth factors that stimulate cancer cells to grow decline with age, which is why ongoing replacement of such hormones in older women seems to increase the risk of breast cancer, and why testicular, breast, uterine, and cervical cancer incidences tend to peak and then plateau or even fall in middle age, instead of continuing to rise like most other cancers. (This is also a cautionary tale about the heterochronic parabiosis phenomenon, considered as a model for long-term anti-aging therapies instead of as a source for factors to be used during brief windows to optimize the administration of cell therapies and transplantation of engineered organs).

Thus, rejuvenating the body will reduce the risk of some cancers (notably, by reversing immunosenescence, clearing out senescent cells, and restoring the structural integrity of the extracellular matrix of our tissues³). In other ways, however, rejuvenation could restore the host tissues’ intrinsic vulnerability to forming new cancers, and to that extent make cancer more of a risk: all those fresh, proliferation-competent cells, and a restored signaling environment full of growth factors. Again we see evidence for this in current cancer patterns. People who develop metastatic colorectal cancer are significantly more likely to suffer disease progression and death when the disease hits them as either young adults or when they have reached today’s older ages, while people in late middle age who are struck with the disease have the lowest risk of both.⁴

And then there is just the sheer passage of time, which gives more time for cancer to develop, irrespective of how the body’s capacity to resist the disease are affected by aging or by rejuvenation treatments that restore youthful resilience. Autopsy studies of men who die in non-cancer-related conditions show that as men age, an increasing number of them actually die with cancer cells in their prostate, even though they die of something else: the numbers are generally found to be around 10%, 30%, 40%, 45%, 70% and 80% of men in their 3rd, 4th, 5th, 6th, 7th and 8th decades of life (respectively).⁵ Doubtless, some of these cells would become dangerous cancers if simply given more time — time that would be bought by eliminating the cellular and molecular damage underlying cardiovascular disease, dementia, and other diseases of aging.

It’s clear that we can’t precisely quantify the residual cancer risk for an individual who had been rejuvenated in other ways, but who had not benefited from rejuvenation biotechnology specifically addressing the central cancer process. But it’s also clear that it would clearly be substantial. It will not be enough to cleave crosslinks from aging tissues, clear aggregated proteins out of aging cells, remove amyloids from aging organs, and so on: we need to make our tissues intrinsically incapable of developing into cancers.

The strategy to do that (discussed in detail in chapter 12 of Ending Aging) is one we call Whole-body Interdiction of Lengthening of Telomeres (WILT). WILT therapy would make our bodies invulnerable to life-threatening cancers by disabling the telomere-maintenance capacity of all the body’s cells. Denied this capacity, cells that had suffered all the mutations needed to become cancers would be unable to replicate enough times to become life-threatening, and would instead self-destruct or become senescent (at which point they could be safely ablated like other senescent cells). Achieving this goal entails the elimination of some indispensable part of the machinery for both of the body’s telomere-maintenance systems: the telomerase system and the less-understood Alternative Lengthening of Telomeres (ALT) system. WILT is ambitious, but it is the only once-and-for-all solution to the cancer program yet proposed — and a future free of all the diseases and debility of degenerative aging depends on putting this plague, specifically, to rest.