Sci. Aging Knowl. Environ., 5 April 2006
Vol. 2006, Issue 7, p. pe8
[DOI: 10.1126/sageke.2006.7.pe8]

PERSPECTIVES

SENS and the Polarization of Aging-Related Research

Douglas A. Gray, and Alexander Bürkle

Douglas A. Gray is at the Ottawa Health Research Institute, Ottawa K1H 8L6, Canada. Alexander Bürkle is in the Department of Biology, University of Konstanz, D-78457 Konstanz, Germany. E-mail: dgray{at}ohri.ca (D.A.G.)

http://sageke.sciencemag.org/cgi/content/full/2006/7/pe8

Key Words: strategies for engineered negligible senescence • Aubrey de Grey • life extension • rejuvenative medicine • SENS challenge • Methuselah mouse prize

In its original conception, what follows would have been a rather conventional meeting report on "Strategies for Engineered Negligible Senescence (SENS), Second Conference" which took place in Cambridge, United Kingdom, in September of 2005. There is nothing at all conventional about SENS (the concept or the meeting of the same name), and a greater purpose may be served by addressing the deepening controversy that SENS has generated, something a conventional meeting report would surely fail to capture. What follows, therefore, are the thoughts of two SENS II conference participants, one (D.A.G.) who is still relatively new to the field and was eager to hear from the leading lights, and the other (A.B.) who has a long-standing interest in biogerontology and who gave a short talk at SENS II.

The author of the SENS concept is Aubrey de Grey, who has organized the SENS meetings to promote his life-extension program in both the scientific and public relations sense. de Grey's argument is that age-related pathology can be attributed to seven types of damage, ranging from DNA mutations to the accumulation of intracellular junk. For each of these types of damage, he has proposed a strategy of molecular or cellular redress (see de Grey Viewpoint). These strategies range from the seemingly plausible (the enzymatic or chemical removal of advanced glycation end products) to the wildly ambitious [the whole-body interdiction of lengthening of telomeres (WILT) strategy of eliminating telomerase and the alternative pathway of telomere lengthening from all mitotic cells as a means of precluding cancer cell proliferation]. It would be fair to say that de Grey recognizes the inherent difficulty of some aspects of SENS, but he appears adamant that all components are possible. Indeed, in collaboration with Technology Review (TR), he has offered a sizable cash reward to anyone who can demonstrate that collectively they are not possible. More about that later.

Like SENS I (the subject of a previous SAGE KE meeting report; see Gray Perspective), the SENS II conference offered a stellar lineup of speakers, many of whom would be considered leading authorities in aspects of what can be loosely categorized as rejuvenative medicine. A partial list of topics discussed at the meeting includes (i) tissue engineering (with presentations from Tony Atala and Buddy Ratner), (ii) nuclear gene engineering (Matthew Porteus), (iii) manipulation of the mitochondrial genome (Bob Lightowlers, Takao Yagi, Rafal Smigrodski, and Henry Weiner), (iv) dealing with cellular aggregates (Bruce Rittman, Janet Sparrow, Jay Jerome, Wendy Jessup, David Rubinsztein, Ralph Nixon, Ana Maria Cuervo, and Roscoe Brady), and so forth. One session dealt with stem cell strategies and featured a spectacular presentation by Woo Suk Hwang, the South Korean cloning expert whose work on human stem cells has subsequently been shown to be fraudulent. The atmosphere in the room was of history in the making (a feeling reinforced by the subsequent and largely political talk given by Gerald Schatten praising Hwang, a collaborator with whom he has since severed relations). Altering the course of history is very much within Aubrey de Grey's own purview (could human immortality be considered anything less?), and the inclusion of Hwang at his very zenith must have been deeply satisfying to de Grey at the time and deeply troubling thereafter. If de Grey is to succeed in his quest to draw in substantial funding for SENS (1), he must deflect any suspicion of the charlatanism that has plagued aging-related research. The sensitivity of legitimate biogerontology researchers to this problem is evident from a position statement saying that "anti-aging" products do not exist and should be considered pseudoscience, signed by 52 eminent researchers (2). On the issue of immortality, the position statement reads as follows: "The prospect of humans living forever is as unlikely today as it has always been, and discussions of such an impossible scenario have no place in a scientific discourse." Surprisingly, Aubrey de Grey was a signatory to this statement.

The potential damage of SENS to mainstream research was recently highlighted by one of the leading figures in biogerontology, Tom Kirkwood. In a Nature book review (3) he wrote: "why is there a pervasive sense that advocates of life extension must make preposterous claims about imminent longevity claims if they are to gain public notice?" and referred to a specific example reported by the BBC, the "laughable claim that the first human who will live to 1000 years is 60 already." The author of that claim was Aubrey de Grey, who in support of the claim referred to the TR "SENS Challenge" in a response posted on the SAGE KE Bulletin Board.

The legitimacy of the SENS approach and the media-friendly face provided by its originator came under attack once again in a multiauthored critique in EMBO Reports (4). Positing that the SENS agenda is "so far from plausible that it commands no respect at all within the informed scientific community," these authors wish to "dissociate themselves from the cadre of those impressed by de Grey's ideas in their present state." This statement is both forceful and ambiguous. It can be read as the relatively benign wish to be placed in a nonoverlapping circle on the Venn diagram of who believes what in aging-related research, or it can be read as a more sinister threat of shunning the apostates. If the authors intended the latter, what are the requirements for admission into the shunned cadre? It could not be attendance at one SENS conference, for some of the signatories have attended. Would attendance at both suffice? Further, is it not possible to express interest in or contribute to some of the scientific objectives of SENS without being judged a SENS acolyte? The objective of eliminating insoluble cellular waste using a bioremediation approach (5) is novel and may have merit in ameliorating the undesirable consequences of aging. The strategy is of interest to one of the authors (D.A.G.; see Gray and Woulfe Review)--could he not endorse this component of SENS, for example, without buying into the whole program, including the possibility and/or advisability of immortality? Actually, one of the authors (A.B.) did not consider speaking at the SENS conference to be an endorsement of the SENS program but instead an active participation in an unconventional conference on aging-related research featuring a number of speakers outside mainstream biogerontology who were bringing in very interesting and inspiring experimental data. Apparently, the same motivation was shared by a number of other SENS speakers and conference participants at large, who were attracted by the novel scientific data they expected to see at the conference, irrespective of the prospects for SENS in life extension.

The TR SENS Challenge is frequently mentioned by Aubrey de Grey (indeed he has devoted an editorial to it in Rejuvenation Research (6), the journal of which he is editor). Half of the wager on offer in the $20,000 TR SENS Challenge derives from the Methuselah Mouse Foundation (which de Grey chairs), and whereas the TR Challenge and the Methuselah Mouse Prize (see "Rewarding Research") both offer cash prizes drawn from a common source, that is where the similarity would appear to end. They are both public relations gambits, but the mouse prize was designed to be won, the TR Challenge to be lost (where the definition of "lost," as determined by de Grey, would encompass situations in which the SENS concept withstood a scientific critique or was simply left uncontested). The mouse prize is without question a clever way of attracting public interest to aging-related research, and by extending the mouse life span its winner will have made a contribution to knowledge. The TR Challenge serves no purpose but to attract attention to Aubrey de Grey and the increasingly bitter dispute with his detractors. Although it allows him to taunt them (baselessly, given the way in which the criteria have been set), it is hard to imagine how this could be a positive thing for future SENS conferences, which are likely to become increasingly populated by media in search of controversial sound bites from its organizer. From all indications, they are likely to come away satisfied. Whether the same will still be said for attending scientists remains to be seen.


April 5, 2006
  1. A. D. de Grey, Resistance to debate on how to postpone ageing is delaying progress and costing lives. Open discussions in the biogerontology community would attract public interest and influence funding policy. EMBO Rep. 6 Spec. No. , S49-S53 (2005).[CrossRef][Medline]
  2. S. J. Olshansky, L. Hayflick, B. A. Carnes, Position statement on human aging. J. Gerontol. A Biol. Sci. Med. Sci. 57, B292-B297 (2002).[Abstract/Free Full Text]
  3. T. Kirkwood, Live longer and prosper. Nature 436, 915-916 (2005).
  4. H. Warner, J. Anderson, S. Austad, E. Bergamini, D. Bredesen, R. Butler, B. A. Carnes, B. F. Clark, V. Cristofalo, J. Faulkner et al., Science fact and the SENS agenda. What can we reasonably expect from ageing research? EMBO Rep. 6, 1006-1008 (2005).[CrossRef][Medline]
  5. A. D. de Grey, P. J. Alvarez, R. O. Brady, A. M. Cuervo, W. G. Jerome, P. L. McCarty, R. A. Nixon, B. E. Rittmann, J. R. Sparrow, Medical bioremediation: Prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res. Rev. 4, 315-338 (2005).[Medline]
  6. A. D. de Grey, The SENS challenge: 20,000 US dollars says the foreseeable defeat of aging is not laughable. Rejuvenation Res. 8, 207-210 (2005).[Medline]
Citation: D. A. Gray, A. Bürkle, SENS and the Polarization of Aging-Related Research. Sci. Aging Knowl. Environ. 2006 (7), pe8 (2006).








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