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  • Zealley B, de Grey ADNJ. Strategies for engineered negligible senescence. Gerontology. 2013;59(2):183-9. Epub 2012 Oct 1. PubMed: 23037635. Categories: SENS Overviews

    Strategies for engineered negligible senescence.

    Gerontology. 2013;59(2):183-9. Epub 2012 Oct 1.

    Strategies for engineered negligible senescence.

    Zealley B, de Grey ADNJ.

    Abstract

    Abstract:

    In this viewpoint, we describe the strategies for engineered negligible senescence (SENS) concept--a simple and appealing model for the design of therapeutic interventions able to meaningfully and persistently reverse the deleterious effects of aging. We go on to outline how current or foreseeable biotechnologies could feasibly be employed to repair every currently identified category of pathogenic damage that accumulates over a human lifespan. Then, briefly, we explain why this goal is not only ethically sound, but can in fact be considered to verge on an ethical obligation. Finally, we review recent progress in some key areas of the SENS platform, including proof-of-concept research sponsored by the SENS Foundation, a charity based in California.

  • de Grey ADNJ. A strategy for postponing aging indefinitely. Stud Health Technol Inform. 2005;118:209-19. PubMed: 16301780. Categories: SENS Overviews

    A strategy for postponing aging indefinitely.

    Stud Health Technol Inform. 2005;118:209-19.

    A strategy for postponing aging indefinitely.

    de Grey ADNJ.

    Abstract

    Abstract:

    It may seem premature to be discussing approaches to the effective elimination of human aging as a cause of death at a time when essentially no progress has yet been made in even postponing it. However, two aspects of human aging combine to undermine this assessment. The first is that aging is happening to us throughout our lives but only results in appreciable functional decline after four or more decades of life: this shows that we can postpone aging arbitrarily well without knowing how to prevent it completely. The second is that the typical rate of refinement of dramatic technological breakthroughs is rather reliable (so long as public enthusiasm for them is abundant) and is fast enough to change such technologies (be they in medicine, transport, or computing) almost beyond recognition within a natural human lifespan. Here I explain, first, why it is reasonable to expect that (presuming adequate funding for the initial preclinical work) therapies that can add 30 healthy years to the remaining lifespan of healthy 55-year-olds will arrive within the next few decades, and, second, why those who benefit from those therapies will very probably continue to benefit from progressively improved therapies indefinitely and thus avoid debilitation or death from age-related causes at any age.

  • de Grey ADNJ. Challenging but essential targets for genuine anti-ageing drugs. Expert Opin Ther Targets. 2003 Feb;7(1):1-5. PubMed: 12556198. Categories: ApoptoSENS, GlycoSENS, SENS Overviews

    Challenging but essential targets for genuine anti-ageing drugs.

    Expert Opin Ther Targets. 2003 Feb;7(1):1-5.

    Challenging but essential targets for genuine anti-ageing drugs.

    de Grey ADNJ.

    Abstract

    Abstract:

    Contrary to what one might conclude from the popular press, anti-ageing drugs do not yet exist, in the sense in which the term 'drug' is normally used. Since a drug is assumed to be effective against its target human pathology and since the vast majority of deaths in the developed world are from ageing-related causes, it is inappropriate to describe something as an anti-ageing drug unless one has good reason to believe that it will appreciably extend the life expectancy of those in the developed world who receive it. A drug that rejuvenates aspects of the aged body but does not increase life expectancy is an antifrailty drug, not an anti-ageing one. This distinction is critical for decision makers in the drug discovery sphere because, while the market for antifrailty drugs (even unproven ones) is large, that for genuine anti-ageing drugs - which, as the author explains, are now foreseeable - will certainly be far larger. In this article, the author surveys the main aspects of age-related degeneration that are believed to be essential targets for genuine anti-ageing drugs - that is, without whose amelioration human life expectancy probably cannot be greatly increased - and some promising strategies for the design of such drugs.

  • de Grey ADNJ. An engineer's approach to the development of real anti-aging medicine. Sci Aging Knowledge Environ. 2003 Jan 8;2003(1):VP1. Also in: The Fountain of Youth: Ethical, Religious, and Existential Perspectives on a Biomedical Goal (S.G. Post and R.H. Binstock, eds.), Oxford University Press, 2003, pp. 249-267. PubMed: 12844502. Categories: SENS Overviews

    An engineer's approach to the development of real anti-aging medicine.

    Sci Aging Knowledge Environ. 2003 Jan 8;2003(1):VP1. Also in: The Fountain of Youth: Ethical, Religious, and Existential Perspectives on a Biomedical Goal (S.G. Post and R.H. Binstock, eds.), Oxford University Press, 2003, pp. 249-267.

    An engineer's approach to the development of real anti-aging medicine.

    de Grey ADNJ.

    Abstract

    Abstract:

    In this Viewpoint, I list the various age-related molecular and cellular changes that are thought to limit mammalian life-span, and I outline a problem-solving approach to reversing these detrimental changes. This approach should help to prevent the development of these age-related changes into life-threatening pathologies and possibly, in due course, allow a large increase in healthy human life expectancy.

  • de Grey ADNJ, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJM, Stock G. Time to talk SENS: critiquing the immutability of human aging. Ann N Y Acad Sci 2002;959:452-462. PubMed: 11976218. Categories: SENS Overviews

    Time to talk SENS: critiquing the immutability of human aging.

    Ann N Y Acad Sci 2002;959:452-462.

    Time to talk SENS: critiquing the immutability of human aging.

    de Grey ADNJ, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJM, Stock G.

    Abstract

    Abstract:

    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.

  • de Grey ADNJ, Baynes JW, Berd D, Heward CB, Pawelec G, Stock G. Is human aging still mysterious enough to be left only to scientists? BioEssays 2002;24(7):667-676. PubMed: 12111727. Categories: SENS Overviews

    Is human aging still mysterious enough to be left only to scientists?

    BioEssays 2002;24(7):667-676.

    Is human aging still mysterious enough to be left only to scientists?

    de Grey ADNJ, Baynes JW, Berd D, Heward CB, Pawelec G, Stock G.

    Abstract

    Abstract:

    The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY Acad Sci 959, 452-462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it.