Today's popular science article for consideration is the usual mix of frustrating and interesting remarks that result when various researchers are convinced to talk to the press on the subject of SENS rejuvenation research. I in no way exaggerate when I say that all approaches to the research of aging, all of the intent in aging research, all of the fundamental disagreements in the field, ultimately revolve around SENS, the Strategies for Engineered Negligible Senescence. The advocacy and the science of SENS are the moral and technological sun in this solar system, for all that many of those orbiting it apparently would rather things were otherwise. Is the point of aging research to cure aging, rejuvenate the old, and greatly extend healthy human life spans? Is the point of aging research to move as rapidly as possible to this goal? In the SENS view, yes, and with specific plans for how the medical control of aging can be realized. Everyone else in the field must be defined by their answers to these questions, and thus by their position on SENS, their differences from the SENS view.
When looking in on this situation from the outside, it is important to realize that (a) more than fifteen years after its introduction, SENS research still represents only a tiny fraction of the research field, (b) that its origins are as an outsider group, its founders entering the research community because they were sufficiently outraged by its lack of action with regard to aging to put aside their own plans, and (c) that only SENS and SENS-like research appears to be producing the basis for cost-effective interventions to address aging as a medical condition. Given this situation, no-one in the field can really ignore SENS, but there are nonetheless a great many who would prefer to.
In one sense, the SENS approach to aging, considering it as the downstream consequence of fundamental damage that should be repaired, has already won the war of ideas: establishment research groups have taken up their own SENS-like agendas based on identifying damage and addressing it in order to turn back aspects of aging. Researchers now argue over how to effectively treat aging rather than remaining silent. Senescent cell clearance, on the SENS list for more than fifteen years on this basis of many lines of research from the past few decades, has in recent years been proven to be a reliable means of reversing numerous aspects of aging in animal studies. It is well on the way to the clinic, under development by a number of funded startup companies. This significant progress has required a fraction of the expenditure to date on, say, calorie restriction mimetic drugs or other ways to slightly slow aging that are diametrically opposed to the SENS philosophy. These are approaches that do not repair root cause damage, but rather try to alter metabolism to slow down accumulation of damage. Senescent cell clearance therapies to date demonstrate very well the point that SENS approaches are cheaper and better, as we should expect of any attempt to repair damage rather than just slow it down.
Yet in another sense, SENS has barely touched on the bigger picture of research and development. It is a tiny fraction of the ongoing work in the field. The vast majority of aging research remains investigative only, with no intention of producing therapies. Only a couple of the characteristically SENS approaches have made it into the mainstream in a big way, senescent cells and amyloid clearance. The first working, real rejuvenation therapies are not yet available in the nearest clinic. Yet tiny fraction as it is, it is the fraction that matters when it comes to results, as the past few years of work on senescent cell clearance has demonstrated. When the only thing that really matters is results, given that the successful treatment of aging is a matter of life and death for all of us, that puts SENS firmly at the center of the field.
SENS as a line of advocacy and set of specific research programs to achieve rejuvenation has helped to fundamentally change the research community since the turn of the century, from one in which no-one could talk about treating aging as a medical condition, to one in which young researchers publish openly on this topic and the first therapies are moving towards the clinic. Yet the researchers whose field has been changed remain on the whole remarkably unwilling to credit any of this to the small community of advocates and researchers who have occupied the central point of strategy and intent in their field. Even those researchers who ten years ago penned a letter dismissing all of SENS as something other than science, the presented evidence for the merits of senescence cell clearance included, find it hard today to admit outright that they were completely wrong. But everything of importance in aging research comes back down to SENS in the end: are research groups working on meaningful ways to turn back aging, or are they just wasting time and funding? What matters more than saving all of the lives lost to degenerative aging? Than preventing all of the suffering caused by degenerative aging? This is a meaningful question in a field that is still in the ragged process of a slow - and apparently sometimes reluctant - change from pure research to applied research, and whose members often seem quite hostile to the SENS advocates who ask these and other pointed questions.
It's just after 10:30 a.m. on a pleasant weekday morning at the SENS Research Foundation, a biotech lab in Mountain View, California. I've come to speak to its chief science officer, Aubrey de Grey. The 54-year-old's long hair, tied back in a ponytail, is turning gray, a change that would be unremarkable if he weren't one of the world's most outspoken proponents of the idea that aging can be completely eradicated. Unlike most scientists, he isn't shy about making bold speculations. He believes, for example, that the first person who will live to be 1,000 years old has most likely already been born. In 2009, de Grey founded the nonprofit SENS Research Foundation, the world's first organization dedicated to "curing" human aging, not just age-related diseases. The organization, which conducts its own research and funds studies by other scientists, occupies an unassuming space in a small industrial park. Its walls are affixed with large, colorful posters illustrating human anatomy and the inner workings of cells.
The basic vision behind SENS is that aging isn't an inevitable process by which your body just happens to wear out over time. Rather, it's the result of specific biological mechanisms that damage molecules or cells. Some elements of this idea date back to 1972, when the biogerontologist Denham Harman noted that free radicals cause chemical reactions, and that these reactions can damage the mitochondria, the powerhouses within cells. De Grey takes this concept further than most scientists are willing to go. His 1999 book argued that there could be a way to obviate mitochondrial damage, slowing the process of aging itself. Now SENS is working to prove this. Its scientists are also studying other potential aging culprits, such as the cross-links that form between proteins and cause problems like arteriosclerosis, and senescent cells that stop dividing but accumulate inside us, secreting proteins that contribute to inflammation. They're looking at damage to chromosomal DNA, and at "junk" materials that accumulate inside and outside cells (such as the plaques found in the brains of Alzheimer's patients). As de Grey's thinking goes, if we could figure out how to remove senescent cells and other damage using approaches like drugs or gene therapy, along with other types of repair, we could potentially keep our bodies vital forever.
This desire to eradicate aging has, in the last decade, inspired a mini-boom of private investment in Silicon Valley, where a handful of labs have sprung up in SENS' shadow, funded most notably by tech magnates. It's this influx of wealth that has brought novel anti-aging theories out of the scientific fringes and into gleaming Silicon Valley labs. De Grey notes that developing the means to make everyone live forever is not cheap. Further, immortality, it turns out, is not such an easy sell: Most people don't like the idea of living forever. "I find it frustrating that people are so fixated on the longevity side effects," de Grey says, clearly irritated. "And they're constantly thinking about how society would change in the context of everyone being 1,000 years old or whatever. The single thing that makes people's lives most miserable is chronic disease, staying sick and being sick. And I'm about alleviating suffering."
Judy Campisi works in Novato at the Buck Institute for Research on Aging, a gleaming profit research institution. "For 99.9 percent of our human history as a species, there was no aging," she says. Humans were very likely to die by our 30s from predation, starvation, disease, childbirth or any number of violent events. Life spans in the developed world have more than doubled over the past century or so, but this hasn't happened through any interventions against aging itself. Rather, it's a byproduct of innovations such as clean water, medication, vaccinations, surgery, dentistry, sanitation, shelter, a regular food supply and methods of defending against predators. A biochemist and professor of biogerontology, Campisi has spent her career studying aging and cancer, and the role senescent cells play in both. She has researched these cells in her lab and published widely on the possible evolutionary reasons they remain in our bodies. She posits that for most of human history, natural selection didn't favor living to old age. Evolution protected younger people so they could pass along their genes, and senescent cells play a very important role.
"One thing evolution had to select for was protection from cancer," she says. "Because we are complex organisms, we have lots of cells in our body that divide, and cell division is a very risky time for a cell because it's easy to pick up a mutation when you are replicating three billion base pairs of DNA." If a cell doesn't divide, there are fewer chances for such a mutation to creep in. "So evolution put into place these very powerful tumor suppressant mechanisms - senescent cells - but they only had to last for 40 years at the most." Senescent cells contribute to inflammation, and "inflammation is the number one risk factor for all diseases of aging, including cancer." The idea that senescent cells contribute to aging was first postulated in the 1960s. Yet 50 years later, scientists still don't entirely understand the role they play. All Campisi can say definitively is that, for most of human history, there was "no evolutionary pressure to make that system better because everybody died young."
When I ask Campisi why some scientists talk about "curing" aging, she says it comes down to getting interventions approved. "There are people who want to consider aging a disease for the purposes of going to regulatory agencies and having a specific drug able to treat a specific symptom, which you can only do if it's recognized as a disease." But Campisi stresses that living forever is not the goal of most research on aging. Instead, she says it's primarily aimed not at life span but "health span" - increasing the number of years that people can remain physically and mentally agile. Campisi has known de Grey for years, collaborates with SENS and even serves on the organization's advisory board. I ask what she makes of his assertion that someone alive today will reach the age of 1,000. "I have to tell you Aubrey has two hats," she says, smiling. "One he wears for the public when he's raising funds. The other hat is when he talks to a scientist like me, where he doesn't really believe that anyone will live to 1,000 years old. No."
In 2006, the magazine MIT Technology Review published a paper called "Life Extension Pseudoscience and the SENS Plan." The nine co-authors, all senior gerontologists, took stern issue with de Grey's position. "He's brilliant, but he had no experience in aging research," says Heidi Tissenbaum, one of the paper's signatories and a professor of molecular, cell and cancer biology at the University of Massachusetts Medical School. "We were alarmed, since he claimed to know how to prevent aging based on ideas, not on rigorous scientific experimental results."
More than a decade later, Tissenbaum now sees SENS in a more positive light. "Kudos to Aubrey," she says diplomatically. "The more people talking about aging research, the better. I give him a lot of credit for bringing attention and money to the field. When we wrote that paper, it was just him and his ideas, no research, nothing. But now they are doing a lot of basic, fundamental research, like any other lab." In marked contrast with de Grey, however, Tissenbaum doesn't see aging itself as the problem. "I don't think it's a disease," she says. "I think it's a natural process. Life and death are a part of the same coin." Meanwhile, scientists are trying to understand why the brain deteriorates over time, losing mass and neural circuitry. Tissenbaum and others are trying to understand these mechanisms, hoping to find new treatments for neurodegenerative diseases. But she doesn't expect any intervention to keep humans healthy forever. "It may be that the brain has a finite life span," she says.