This popular press article covering one arm of the longevity science research community in the US is better than most, in that it seems moderately accurate when it comes to identifying some of the people who matter and a few of their views on the topic. Of course in any such article you are flying over the terrain at a great height, seeing only the mountaintops, and little of what really makes the place live and breathe. You are also missing the other regions you cannot see. My chief complaint here is unfortunately a typical one, in that the author presents the SENS rejuvenation research program in a fairly disingenuous way. This is no way to treat the class of research and development most likely to turn back aging in the near future.
For decades, the solution to aging has seemed merely decades away. In the early nineties, research on C. elegans, a tiny nematode worm that resembles a fleck of lint, showed that a single gene mutation extended its life, and that another mutation blocked that extension. The idea that age could be manipulated by twiddling a few control knobs ignited a research boom, and soon various clinical indignities had increased the worm's life span by a factor of ten. Death would no longer be a metaphysical problem, merely a technical one. The celebration was premature. Gordon Lithgow, a leading C. elegans researcher, told me, "At the beginning, we thought it would be simple - a clock! - but we've now found about five hundred and fifty genes in the worm that modulate life span. And I suspect that half of the twenty thousand genes in the worm's genome are somehow involved."
For us, aging is the creeping and then catastrophic dysfunction of everything, all at once. Our mitochondria sputter, our endocrine system sags, our DNA snaps. Our sight and hearing and strength diminish, our arteries clog, our brains fog, and we falter, seize, and fail. Every research breakthrough, every announcement of a master key that we can turn to reverse all that, has been followed by setbacks and confusion. A few years ago, there was great excitement about telomeres, DNA buffers that protect the ends of chromosomes just as plastic tips protect the ends of shoelaces. As we age, our telomeres become shorter, and, when these shields go, cells stop dividing. If we could extend the telomeres, the thinking went, we might reverse aging. But it turns out that animals with long telomeres, such as lab mice, don't necessarily have long lives - and that telomerase, the enzyme that promotes telomere growth, is also activated in the vast majority of cancer cells. The more we know about the body, the more we realize how little we know.
In the murk of scientific inquiry, every researcher looks to a ruling metaphor for guidance. Aubrey de Grey likes to compare the body to a car: a mechanic can fix an engine without necessarily understanding the physics of combustion, and assiduously restored antique cars run just fine. De Grey is the chief science officer of Silicon Valley's SENS Research Foundation, which stands for Strategies for Engineered Negligible Senescence - a fancy way of saying "Planning Your Comprehensive Tune-up." De Grey has proposed that if we fix seven types of physical damage we will be on the path to living for more than a thousand years. "Gerontologists have been led massively astray by looking for a root cause to aging, when it's actually that everything falls apart at the same time, because all our systems are interrelated. So we have to divide and conquer." We just need to restore tissue suppleness, replace cells that have stopped dividing and remove those that have grown toxic, avert the consequences of DNA mutations, and mop up the gunky by-products of all of the above. If we can disarm these killers, de Grey suggests, we should gain thirty years of healthy life, and during that period we'll make enough further advances that we'll begin growing biologically younger. We'll achieve "longevity escape velocity."
De Grey vexes many in the life-extension community with his prophetic air of certainty. His 2007 book, "Ending Aging," is replete with both exacting research into the obstacles to living longer and proposed solutions so ambitious that they resemble science fiction. De Grey's fix for mitochondrial mutation, for instance, is to smuggle backup copies of DNA from the mitochondria into the vault of the nucleus, which evolution annoyingly failed to do-probably because the proteins needed in the mitochondria would ball up during their journey through the watery cell body. His fix for that, moving the DNA one way and the proteins that it produces another, amounts to a kind of subcellular hokey pokey. A number of scientists praise de Grey for anatomizing the primary threats, yet they see troubleshooting all seven pathways through such schemes - and you have to troubleshoot them all for his plan to work - as a foredoomed labor. Biogerontologist Matt Kaeberlein said, "It's like saying, 'All we have to do to travel to another solar system is these seven things: first, accelerate your rocket to three-quarters of the speed of light... ' "
Ned David is a biochemist and a co-founder of a Silicon Valley startup called UNITY Biotechnology. UNITY targets senescent cells - cells that, as they age, start producing a colorless, odorless, noxious goo called SASP, which UNITY's researchers call "the zombie toxin," because it makes other cells senescent and spreads chronic inflammation throughout the body. In mice, UNITY's treatments delay cancer, prevent cardiac hypertrophy, and increase median life span by thirty-five per cent. "We think our drugs vaporize a third of human diseases in the developed world." Pharma and biotech companies make money only if they treat a disease, and, because aging affects everything, the FDA doesn't recognize it as an "indication" susceptible to treatment (or to insurance-company reimbursement). So UNITY is taking aim at glaucoma, macular degeneration, and arthritis.
It has to be said that allotopic expression of mitochondrial genes in the cell nucleus is a poor example to pick for something that is alleged to be a doomed labor. The work has been accomplished for three of the thirteen genes needed; this is a capability that exists, and is underway towards completion. The allotopic expression of ND4 is the basis for a therapy that is currently going through clinical trials in Europe. Yes, it takes work, but so does everything else. This is one of the things that frustrates me immensely about many of the critics of SENS - they willfully ignore the progress that has been made, pretending it doesn't exist.
And that isn't even to start in on what is said - and, more importantly, not said - about senescent cell clearance, something that de Grey and other SENS advocates have been promoting as a path to treat aging for the past fifteen years, on the basis of strong evidence. It is right there in the SENS outline; hard to miss. Targeted removal of senescent cells has finally taken off these past few years, the evidence for a significant impact on aging has grown to be nigh irrefutable, and near everyone in the research community is enthused. Yet SENS and many researchers' past rejection of senescent cell clearance as a part of SENS is swept under the rug, never to be mentioned. It is unconscionable behavior, and it happens here: despite covering UNITY Biotechnology, the senolytics company, no mention of senescent cells is made in connection with the SENS vision. It takes some brass to claim SENS to be a doomed effort and then roll right into a discussion with one of the UNITY co-founders on the topic of removing senescent cells to treat aging.