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My Turn: Dartmouth science, Chinese billionaires and Tolkien’s elves



For the Monitor
Saturday, November 25, 2017

Bowhead Whales can live more than 230 years. Greenland sharks live more than 400. Various other non-vertebrates live even longer, but first let’s catch up to our mammal cousins. If we delay decrepitude and senility for two centuries, then suddenly health care costs, Social Security, how to find time to binge-watch that Netflix series, etc., become solved problems.

The Bowhead’s health span is impressive when you consider that it has 500 times as many cells as we do. That multiplied by the two-century life span means that the whale is more than a thousand times more resistant to cancer than our supposedly advanced species.

Yet when you study the whales’ cells (as I did under the flickering red fluorescent lights of the Shay-Wright cell-culture lab in the early 2000s), they don’t look much different from ours. They also have p53 as a checkpoint protein, their non-stem cells also have telomeres that shorten and serve as an aging clock.

Later researchers sequenced the Bowhead genome, ran protein arrays, etc. They found things that suggest better DNA repair, but overall not too much difference between a whale and a cow (their closer relative) or human cell.

This wide discrepancy in lifespans between apparently similar organisms is common in nature. There are rodents that live 10 times longer than other similar rodents. As Dr. Austad realized two decades ago, animals that can evade predators and disease will often live much longer than species in more risky environments.

Aging is a program. A self-destruct program, written into the DNA memory in each of our cells. Rewrite the program, even tweak the epigenetic expression, and you rewrite the health span.

Different humans have different programs. A mutation in some of the Berne Amish in Indiana adds about 10 years to their average life span. The mutants don’t have an extra gene; their longevity comes from one of their SERPINE1 genes being inactive. It is the absence of a death-program gene that extends their lives.

We have been reprogramming cell programs in the lab for a long time. In the Shay-Wright lab, we added active telomerase genes to cells from many species of mammals, birds, reptiles and grad students. In every genera we were able to immortalize the cells.

A telomerized cell no longer runs out of telomere and senesces. It can replicate forever. That’s not 100 percent a good thing, of course, if the cell turns cancerous. But using drugs to temporarily activate telomerase allows us to reset the telomeres in each cell back to their optimum length. Sierra Sciences has developed two series of telomerase activation drugs, and is working on more.

Another approach to extending life span is caloric restriction. Of course anyone who suggests that Americans could eat less must immediately be driven from our country, nay, our solar system!

Fortunately, there are ways to mimic caloric restriction with drugs, consistent with our traditional culture and mores.

Okay, don’t call them drugs (unless you want to have the FDA lock them away for 19 years), but wholesome natural nutrients. Nicotinamide riboside raises the level of NAD+ in human cells. This leads to sirtuins doing lots of things that I can’t cover in an op-ed. But the result is that the cells, like American voters, become confused into thinking that they are in an environment low on resources and opportunities. They regenerate their mitochondria, reduce their self-destructive behavior and try to outlive what they think is a crisis.

The U.S. company that makes nicotinamide riboside, Chromadex, has recently expanded into China with funding from Chinese billionaires Li Ka-Shing and Solia Chau. Their scientific advisers include Dr. Charles Brenner, former associate director for basic sciences at Norris Cotton Cancer Center.

They have completed a Phase 2 study on the health effects of NR, and it will be published in a peer-reviewed journal at the usual pace of 21st-century science (which is 10 months – 10 months to get something from one computer in a lab to another in the web server of a “journal” – the same time it took to publish information 30 years ago).

Anyway, soon we’ll know something about metabolic interventions in human aging.

The future of our health spans has little to do with the current “health care system.” Real change is being driven by these disruptive researchers and small startup companies that are attacking the underlying biology of aging and cancer.

Like Tolkien’s elves, we may be living in our New Hampshire forests for a very long time.

(Bill Walker worked as a technologist in cell biology labs at UTSW and Mayo Clinic Rochester, and now works at M2S in West Lebanon.)