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All scientists are acutely aware of the profound challenge that they face when communicating scientific findings to nonscientists, especially when great uncertainty is involved and when the topic is of personal interest to the general public. Simplification of the issues--sometimes extending to a degree of oversimplification--is a sad but generally recognized necessity. It is not, however, a necessity when scientists communicate with each other, and when that happens, the explanation may lie elsewhere: either in the speaker's vested interests or in overconfidence on the speaker's part in the extent to which he or she has grasped the topic under discussion. Both these explanations are serious allegations and must not be made without good reason, not least because an alternative explanation is often the entirely legitimate preference for scientific "shorthand." However, when a general tendency toward oversimplification emerges within an expert community, not only in informal interactions but in learned publications, the field in question can suffer a loss of reputation for rigor, which may especially infect younger scientists joining that field (or contemplating joining it). I feel that this has occurred to a dangerous degree within biogerontology in respect of the way in which the effect of the environment on the rate of aging-whether that of an individual organism or of a lineage-is described. There are still important controversies in that area, but I refer here strictly to issues concerning which a thorough consensus exists. In this essay I highlight some fundamental tenets of biogerontology that are frequently, and to my mind problematically, mis-stated by many in this field in their printed pronouncements. Greater precision on these points will, I believe, benefit biogerontology at many levels, avoiding confusion among biogerontologists, among other biologists, and among the general public.

The early days of biogerontology were blessed with an undiluted forthrightness concerning the field's ultimate goals, epitomized by its leaders. Luminaries from Pearl to Comfort to Strehler declared the desirability of eliminating aging with no more diffidence than that with which today's oncologists aver that they seek a cure for cancer. The field's subsequent retreat from this position garnered a modicum of political acceptability and public financial support, but all biogerontologists agree that this fell, and continues to fall, vastly short of the funding that the prospect of even a modest postponement of aging would logically justify. The past 20 years' discoveries of life-extending genetic manipulations in model organisms have weakened the argument that a policy of appeasement of the public's ambivalence about defeating aging is our only option; some of the biogerontologists responsible for these advances have espoused views of which our intellectual forefathers would be proud, without noticeably harming their own careers. With the recent emergence of a detailed, ambitious, but practical roadmap for the comprehensive defeat of aging, this process has moved further: our natural and most persuasive public stance is, more than ever, to reembrace the same unassailable logic that served pioneering biogerontologists perfectly well. In particular, we are in a position to explain that the disparate strands of contemporary biomedical gerontology are not in conflict, but rather that they constitute a portfolio of approaches with a range of potential efficacies and degrees of difficulty of implementation, which can save more lives together than any can save individually, and all of which thus merit intensive pursuit.

Criticisms of demographers by other demographers have become frequent in scientific literature, generally consisting of accusations that trends observed in the recent past have been extrapolated unjustifiably into the future. Demographers, along with their colleagues in the actuarial profession, are in an invidious position in this regard, knowing full well that extrapolation is almost always only minimally justifiable, but knowing also that their readers, colleagues, and sources of funding tend to be much more interested in the future than in the past. It is unfortunate that, while actuaries typically resolve this dilemma by emphasizing the limitations of their methods and thereby lowering expectations that their predictions will be accurately fulfilled, demographers are more prone to respond combatively, attempting to reinforce the credibility of their extrapolations by recourse to data from areas in which their expertise is less tested, such as biology. This is valuable in that it raises the profile of the debate on the likely rate of scientific progress relevant to mortality rates, but it also runs the risk of lowering the technical quality of that debate, by telling policy makers and the public what they want to hear and thereby entrenching their expectations without recourse to the relevant biological facts. Extrapolations based on plausible sequences of scientific advances and the sociopolitical responses to them, summarized in this article, have led to the prediction of four-digit life expectancies of cohorts born in the 21st century and possibly even in the 20th. This prediction has attracted inevitable ridicule from prominent demographers, but being founded on science and sociology rather than on history it may be much more reliable than the extrapolations that those demographers presently prefer.

Aging is unpopular with the general public-but, it would seem, only up to a point. Treatments that claim (sometimes justifiably) to extend the total and/or healthy life span of elderly people, or even just make them look younger, are welcomed with open wallets throughout the world. If, however, one suggests to the typical nonbiologist-or even to the typical nongerontologist biologist-that we should therefore aim, in due course, to take this desire to its logical conclusion and bring aging under the same degree of control that we currently have over most infectious diseases, one is nearly always met with strong and sometimes strident opposition. I argue here that the prevalence of this outright irrationality is largely the fault of gerontologists themselves. Most people harbor a deep-seated fear of profound change in their lives and embrace it only after extensive soul-searching to convince themselves of its benefit. It cannot and should not be denied that a postaging world would be as profoundly different from today's as we can imagine. Hence, when given the opportunity to postpone sober consideration of its pros and cons, most people leap at that opportunity. It is provided to them by the nearly universal refusal of gerontologists to speculate about the timescales within which truly effective rejuvenation therapies may be developed. I suggest that this reticence, while appropriate in purely scientific fields, is hugely irresponsible in a biomedical discipline, because of its potential to delay the development of such therapies by denying them the funding that would be forthcoming if society had greater optimism concerning their foreseeability. Arguments that such funding, and/or the public's trust in scientists, would be short-lived if timescale predictions were not borne out are too flimsy to outweigh this. A further danger is the avoidable loss of life following the development of rejuvenation therapies that would result from inadequate ability to provide them universally; here again, scientists today can minimize this loss of life by agitating for forward planning by government, which will only occur when policymakers' minds are concentrating on timescale predictions.

Despite enormous effort, progress in reducing mortality from cancer remains modest. Can a true cancer "cure" ever be developed, given the vast versatility that tumors derive from their genomic instability? Here we consider the efficacy, feasibility, and safety of a therapy that, unlike any available or in development, could never be escaped by spontaneous changes of gene expression: the total elimination from the body of all genetic potential for telomere elongation, combined with stem cell therapies administered about once a decade to maintain proliferative tissues despite this handicap. We term this therapy WILT, for whole-body interdiction of lengthening of telomeres. We first argue that a whole-body gene-deletion approach, however bizarre it initially seems, is truly the only way to overcome the hypermutation that makes tumors so insidious. We then identify the key obstacles to developing such a therapy and conclude that, while some will probably be insurmountable for at least a decade, none is a clear-cut showstopper. Hence, given the absence of alternatives with comparable anticancer promise, we advocate working toward such a therapy.

Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates. This accumulating damage ultimately drives age-related degeneration. Interventions can be designed at all three stages. However, intervention in metabolism can only modestly postpone pathology, because production of toxins is so intrinsic a property of metabolic processes that greatly reducing that production would entail fundamental redesign of those processes. Similarly, intervention in pathology is a "losing battle" if the damage that drives it is accumulating unabated. By contrast, intervention to remove the accumulating damage would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely. We survey the major categories of such damage and the ways in which, with current or foreseeable biotechnology, they could be reversed. Such ways exist in all cases, implying that indefinite postponement of aging--which we term "engineered negligible senescence"--may be within sight. Given the major demographic consequences if it came about, this possibility merits urgent debate.