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Substantial life extension and quality of life

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Abstract

Caloric restriction mimetics (CRMs) are emerging biotechnologies that promise to substantially enhance human lifespan. CRMs like resveratrol, metformin and rapamycin have been extensively tested in animals and have undergone clinical trials in humans, with positive indications for extended lifespan. This raises important questions for individuals and society: Is it really better to have a longer life? Would life-extending biotechnologies contribute to social problems like overpopulation? Will CRMs increase the longevity gap between haves and havenots? Worryingly, many of these concerns are neglected, both in individual choices and in social policy. The imminent availability of interventions that substantially increase lifespan creates an urgent need for informed individual and policy decisions. As a step in this direction I focus on whether life extension by CRMs would make a person's life better. One of the greatest fears in this regard is that lifespan augmenting technologies would result in a prolonged old age, and an extended period spent in intolerably poor health. On the basis of empirical studies, I claim that CRMs will not result in worse health than is normally the case in old age. However, since they slow down the ageing process they will extend the period in which one is more susceptible to the diseases of old age. Though preferable to substantially worse health, prolonged old age may seem undesirable to some. I make the case that CRMs would most likely improve one's quality of life. This is because they would add to life's value by increasing the number of years spent in good health. Moreover, I argue that even years spent in worse health, above a certain level, can contribute to the goodness of life. These considerations mean that this emerging biotechnology is likely to increase both the quantity and quality of life, and should provide part of the basis for informed decisions about the individual consequences of extending lifespan using CRMs.

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Studies on mice and rats have demonstrated that calorie restriction (CR) slows primary aging, has a protective effect against secondary aging, and markedly decreases the incidence of malignancies. However, the only way to determine whether CR "works" in humans is to conduct studies on people. Such studies are difficult to perform in free-living people. While research on CR in humans is still at an early stage, a modest amount of information has accumulated. Because it is not feasible to conduct studies of the effects of CR on longevity in humans, surrogate measures have to be used. Preliminary information obtained using this approach provides evidence that CR provides a powerful protective effect against secondary aging in humans. This evidence consists of the finding that risk factors for atherosclerosis and diabetes are markedly reduced in humans on CR. Humans on CR also show some of the same adaptations that are thought to be involved in slowing primary aging in rats and mice. These include a very low level of inflammation as evidenced by low circulating levels of c-reactive protein and TNFalpha, serum triiodothyronine levels at the low end of the normal range, and a more elastic "younger" left ventricle (LV), as evaluated by echo-doppler measures of LV stiffness.
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Caloric restriction remains the only nongenetic intervention that has been consistently and reproducibly shown to extend both average and maximal lifespan in a wide variety of species. If shown to be applicable to human aging, it is unlikely that most people would be able to maintain the 30-40% reduction in food intake apparently required for this intervention. Therefore, an alternative approach is needed. We first proposed the concept of caloric restriction (CR) mimetics in 1998. Since its introduction, this research area has witnessed a significant expansion of interest in academic, government, and private sectors. CR mimetics target alteration of pathways of energy metabolism to potentially mimic the beneficial health-promoting and anti-aging effects of CR without the need to reduce food intake significantly. To date, a number of candidate CR mimetics including glycolytic inhibitors, antioxidants and specific gene-modulators have been investigated and appear to validate the potential of this approach.
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