SciTech

Aubrey De Grey

Aubrey de Grey, a Cambridge, U.K.-based​ biogerontologist, visited Carnegie Mellon on Feb. 12th to give a talk, titled “Prospects for defeating aging altogether.” The lecture, sponsored by AB Lectures, centered around a collection of techniques he dubs Strategies for Engineered Negligible Senescence (SENS), which de Grey claims holds the promise for potentially limitless extension of life. “People like to characterize me as an immortalist,” reflected de Grey. “What I’m interested in doing is helping people from getting sick.” Life extension research is a controversial topic — partly because the National Institutes of Health (NIH) does not classify aging as a disease. According to Danith Ly, assistant Professor of Chemistry here at Carnegie Mellon, there is no known “aging regulon,” no molecule whose presence unequivocally means that aging is taking place.

According to de Grey, “Aging is, without a doubt, a side effect of being alive in the first place.” Metabolism, the complex series and cycles of processes involving chemical energy that define life, produces various types of damage.
When enough damage accumulates, a large-scale problem surfaces, which is then called a disease. When considering strategies for the intervention of elderly-onset diseases, one might look to the study of metabolism.

If it were understood how metabolism and, more specifically, its by-products, negatively impact individual cells, it would be possible to make therapies targeting those damaging pathways. Unfortunately, metabolism is not understood very well, and what is already known paints a complex picture.
Since we have little hope of understanding metabolism, de Grey contends that we have much less of a chance at improving it. Another strategy, then, might be to investigate better treatments of the diseases associated with old age, the study of geriatrics. The problem is that “[treatment] gets harder as the patient gets older, because the precursors of the targets of the geriatric approach are continuing to accumulate.”

The hope of successful treatment dwindles as the patient ages. As de Grey claims, geriatrics is a short-term strategy, merely “slowing down the rate at which damage converts into pathology.” Metabolism is not understood well enough to be improved upon, and so it is not possible to prevent damage from occurring. The disease, resulting from large concentrations of damage, can only be reined in for a while — some time can be bought — before other problems stemming from the still-present damage become apparent.

Given that it is difficult either to prevent the damage from occurring or to control the effects of damage, de Grey offers a third strategy: limit the damage. As long as damage is kept below a certain threshold, he claims, we can indefinitely postpone the corresponding disease, a process that de Grey calls “the engineering approach.” He claimed that all types of damage have been isolated and that there are only seven of them. For each of these types of damage, de Grey outlined treatments in various stages of development that hold the promise to moderate or negate the damage.
These treatments are what de Grey collectively refers to as SENS, which he opines may lead to “robust human rejuvenation,” the total circumvention of the aging process. The Methuselah Foundation, of which he is a co-founder, offers a cash prize to the research team that extends the life of the common laboratory mouse, Mus musculus.

The ultimate motive of the prize is to develop techniques for robust mouse rejuvenation, which de Grey believes could be translated to human application within 10 years of discovery. His beliefs have stirred up passionate debate among biologists. In February 2005, the MIT Technology Review published “Do You Want to Live Forever?” In his article, Sherwin Nuland, a professor at Yale University’s School of Medicine, portrayed de Grey as a well-meaning scientist, but whose “grand design will almost certainly not succeed. Were it otherwise, he would surely destroy us in attempting to preserve us.” According to a piece written by Jason Pontin, then the editor-in-chief and publisher of Technology Review, in his blog, many readers of Technology Review were not satisfied with Nuland’s treatment of the topic. In response to the criticism, the publication issued the SENS Challenge, offering $20,000 to the team that could convincingly demonstrate the infeasibility of SENS to a panel of independent judges. No team was successful, and in “Is Defeating Aging Only a Dream?” — published in the Technology Review in July 2006 — the author related the opinion of the panel: “SENS is a collection of hypotheses that have mostly not been subjected to [the scientific] process and thus cannot rise to the level of being scientifically verified.... SENS exists in a middle ground of yet-to-be-tested ideas that some people may find intriguing but which others are free to doubt.”

Regardless, there have been some indications that de Grey’s hypotheses may not be as far-fetched as is thought. Lysosomes are the waste disposal sites of the cell — if these are not working properly, then toxic waste builds up and damages the cell. In a study published in August 2008 in Nature Medicine, Cong Zhang and Ana Cuervo of Yeshiva University reported that liver function in rats can be maintained for longer when additional copies of certain genes related to the function of the liver cells’ lysosomes are introduced.

By showing that the age-related dysfunction of a certain organ can be postponed, they give hope to the possibility that other gene therapies may be able to target the aging of other organs of the body. When asked what the common person could do to spur research on the aging problem, de Grey responded “evangelization.”
According to de Grey, society is experiencing an “aging trance” — a hypnosis that has us bound to the idea that aging is inevitable and moreover a good thing, and that therefore we should not fund life extension research. He suggests that a younger, less entrenched audience may be able to change attitudes toward the inviolability of the aging process.