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LETTER TO THE EDITOR |
Department of Anatomy University of California, San Francisco E-mail: len{at}gene.com
School of Public Health University of Illinois at Chicago E-mail: sjayo{at}uic.edu
New England Centenarian Study Boston Medical Center E-mail: thperls{at}bu.edu
Michael Rae's complaint of "imbalance" in the choice of authors for the two issues of the Journal of Gerontology: Biological Sciences that we guest-edited (1) is without merit because several of the people that he has specifically named or quoted, and others who he might have named, were asked to contribute. They chose not to.
Rae's characterizations of Hayflick as an "extreme ... pessimist" and Olshansky as a "moderate ... pessimist" are both inaccurate. Rae fails to understand that intervention in the aging process must be distinguished from intervention in the determinants of longevity. Both could produce serious unintended consequences. It would serve Rae well to read carefully some of what has been written on this subject (2–4). He might then appreciate why Hayflick and others believe themselves to be both pragmatists and "extreme optimists" because they are persuaded to believe that the low probability of intervening in the human aging process during this century is a blessing.
It is unclear why Rae views Olshansky as a pessimist. In his two Science articles devoted to the future of human life expectancy (5,6), Olshansky stated unambiguously that current technologies and lifestyle interventions could lead to 55% reductions in death rates at all ages from all causes combined within the coming decades in low mortality populations—a feat that would rival the elimination of both cancer and heart disease. It is hard to imagine how this view could be construed to be pessimistic.
Rae's unfortunate reaction of "embarrassment" in reading Hayflick's contribution should be evaluated in light of the fact that this article was, as were all other articles, processed using "... the normal standards of external peer review ..." that Rae champions and that have been the hallmark of the Journals of Gerontology since their inception. All of the reviewers are professional researchers in biogerontology who clearly failed to suffer embarrassment because they approved of Hayflick's offering. Rae, a member of the Calorie Restriction Society is, according to them, a "core-scientific researcher ... conducting an on-going study on the effects of Calorie Restriction (CR) in humans" (7).
Rae's assertion that "... retardation of aging has already been accomplished in entities far more complex than an automobile ..." like "... rodents and other laboratory animals ... through caloric restriction (CR)" could only be made by someone who has failed to understand the main thrust of Hayflick's paper and the definitions of terms that he provided. He also ignores the fundamental differences between longevity determinants and the aging process. Age changes are a fundamental property of matter, and neither CR nor any other proposed intervention has been demonstrated to reverse, arrest, or slow the process once it has begun. Failure to agree on biomarkers of aging is only one of several major impediments. On the other hand, manipulation of longevity determinants to prolong life in laboratory animals is a fact.
Even if intervention in the aging process could be estimated empirically by utilizing the actuarial rate of aging (which is the only way that biological aging can be estimated today), a CR experiment on humans would not only require a statistically large sample, but experimenters and participants would also be faced with serious ethical questions. In addition, careful monitoring of participants would be required over many decades to detect unwanted physical or mental side effects. This would be equivalent to mounting phase II and phase III clinical trials for drug safety and efficacy and would incur costs well into the hundreds of millions of dollars. Furthermore, close to a century of observation would be required to determine whether the participants lived significantly longer than people not on CR.
More importantly, the opposite interpretation of the usual CR experiments is equally tenable. That is, the overconsumption of calories (which only occurs with human intervention) reduces longevity. The almost universal laboratory finding that CR increases longevity may simply have revealed the life-shortening effect of gluttony rather that the life-extending effect of CR.
Rae's gratuitous choice of terms and phrases such as "errors of logic," "gaps in reasoning," "Hayflick's intonation," "a particularly glaring example of a lack of critical review," and "Neither Hayflick nor the Editors of this issue can be ignorant of this robust finding" speak more to Rae's preference for empty, ex cathedra assertions than it does to facts. It would have been far more productive for him to present data that could have invoked scientific debate.
Contrary to Rae's placement of blame for many of his unfounded complaints on "the Editors (who) chose to primarily present articles devoted to a facile critique of the foibles of the current pseudoscientific ‘anti-aging’ marketplace," we invited credentialed authors who represented a wide range of views. The failure of some potential authors to accept our invitation is a matter over which no editor has control. But, the Journals of Gerontology do have control over an uncompromising peer review process to which it scrupulously adhered. As for Rae's belief that "the readership of a gerontological journal is already quite aware that neither growth hormone injections nor vitamin C capsules retard biological aging," we find no evidence proffered by him of polling data that support his unsubstantiated assertion.
Rae's claim that it is a "fact that attempts to retard aging in mammals via hormesis have consistently failed (although they have often normalized survival in genetically or environmentally disfavored organisms)" reflects an unfamiliarity with the enormous hormesis literature. Although it will fly in the face of his world view, Rae might benefit from reading the April 2001 issue of the Belle Newsletter (8).
Rae further reveals his failure to have read and understood the contents of both issues (1) by his assertion that "By monopolizing the allocation of space to such distractions, the second issue failed to explore its stated subject: avenues by which biological aging might, in fact, be delayed, slowed, arrested, or reversed." No major scientifically based approach that might affect longevity was omitted in the two special sections of these issues, including his favorite: caloric restriction. What we believe Rae is actually objecting to, and is unwilling to state, is that none of the authors presented data that confirm his several biases.
Rae offers his opinion that "some of the finest minds in aging research have proposed and updated a far more ambitious therapeutic program to restore youthful organismal molecular fidelity and functionality in aged humans. Th(is) ... led the authors to the conclusion ‘that indefinite postponement of aging—which we term ‘engineered negligible senescence’—may be within sight. One has yet to hear a cogent rejoinder to these proposals from the ‘anti-aging’ skeptics."
The "cogent rejoinder" that Rae seeks is this: No one is conducting, or is planning to conduct, an "ambitious therapeutic program to restore youth ... in aged humans" not only because the benefits of doing so are questionable but also because sufficient faith that the proper design and implementation of such a study, in which the principles of ethics, statistics, and proof of safety and efficacy can be observed, has persuaded no one to risk the necessary investment in time and resources.
Rae may be interested to know that one of the "fine mind(s) in aging research," to which he alludes, was invited to submit a paper, but it did not pass independent external peer review conducted by the Editor (not the Guest Editors).
Those of us who have suffered long from less than "fine minds in aging research," but who, in spite of this failing, have dedicated ourselves to the conduct of decades of original research in this field make no apologies for the way in which we guest-edited the special sections of the June and July issues (1).
References
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