It's Never Too Late: Calorie Restriction is Effective in Older Mammals

Rae, Michael J.

doi:10.1089/154916804323105026

Cited by 20 publications

(13 citation statements)

References 19 publications

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“…In that time period, the control group spent a total of 219 days in the infirmary, and 13 deaths occurred, while the corresponding figures in the CR group were 123 days and 6 deaths respectively. These results are all the more striking when one considers the reasonable expectation that an elderly, presumably frail study cohort might have adapted poorly to CR (as is seen under suboptimal conditions in older rodent populations (Weindruch and Walford 1982;Rae 2004).…”

Section: Brass Monkey Weathermentioning

confidence: 94%

“…Recently, and somewhat counterintuitively, it has been found that this antiaging effect is fully available even at relatively advanced ages, after substantial molecular aging damage has already accumulated Rae 2004). The standard extrapolation of these findings, which available interspecies CR data seem prima facie to uphold, is that a given degree of CR imposed on an animal of a given species leads to a similar extension of LS expressed as a proportion of the species maximum LS: what de Grey terms Bthe proportionality principle^(PP).…”

Section: Introductionmentioning

confidence: 99%

“…While juvenile rodents respond robustly to the simple feeding of reduced portions of the AL diet, this protocol has been repeatedly demonstrated to fail in adult and older organisms; full provision of essential nutrients appears to be essential for effective anti-aging CR in these animals(Weindruch and Walford 1982;Dhahbi et al 2004;Rae 2004).…”

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confidence: 99%

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You don't need a weatherman: famines, evolution, and intervention into aging

Rae¹

2006

AGE

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Calorie restriction (CR) is the most robust available intervention into biological aging. Efforts are underway to develop pharmaceuticals that would replicate CR's anti-aging effects in humans ("CR mimetics"), on the assumption that the life- and healthspan-extending effects of CR in lower organisms will be proportionally extrapolable to humans (the "proportionality principle" (PP)). A recent argument from evolutionary theory (the "weather hypothesis" (WH)) suggests that CR (or its mimetics) will only provide 2-3 years of extended healthy lifespan in humans. The extension of healthy human lifespan that would be afforded by intervention into aging makes it crucial that resources for therapeutic development be optimally allocated; CR mimetics being the main direction being pursued for interventive biogerontology, this paper evaluates the challenge to the potential efficacy of CR mimetics posed by the WH, on a theoretical level and by reference to the available interspecies data on CR. Rodent data suggest that the anti-aging effects of CR continue to increase in inverse proportion to the degree of energy restriction imposed, well below the level that would be expected to be survivable under the conditions under which the mechanisms of CR evolved and are maintained in the wild. Moreover, the same increase in anti-aging effects continues well below the point at which it interferes with reproductive function. Both of these facts are in accordance with the predictions of evolutionary theory. Granted these facts, the interspecies data-including data available in humans-are consistent with the predictions of PP rather than those of the WH. This suggests that humans will respond to a high degree of CR (or its pharmaceutical simulation) with a proportional deceleration of aging, so that CR mimetics should be as effective in humans as CR itself is in the rodent model. Despite this fact, CR mimetics should not be the focus of biomedical gerontology, as strategies based on the direct targeting of the molecular lesions of aging are likely to lead to more rapidly developable and far more effective anti-aging biomedicines.

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Section: Brass Monkey Weathermentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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You don't need a weatherman: famines, evolution, and intervention into aging

Rae¹

2006

AGE

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“…For example, a 1994 European clinical study on non-obese, middle-aged subjects under a 10-week, 20% energy reduction (Velthuis-te Wierik et al 1994), and the 2-year Biosphere experience (Walford et al 1999(Walford et al , 2002), produced promising human data on CR's efficacies (Rae 2004). Further, a recent report (Fontana et al 2004) shows CR's beneficial effects, including the suppression of an atherosclerosis and inflammation biomarker in humans, solidifying the possibility of CR's extension of human longevity.…”

Section: Data On the Cr's Effect In Humansmentioning

confidence: 99%

“…In my view, a couple of reasons could be at the root of the controversy (Phelan and Rose 2005;Rae 2004). The most obvious reason is that at present, there are no experimental human data that permits us conclude that CR extends maximum lifespan, because the CR paradigm has not been tested out under the same wellcontrolled conditions on human subjects as with rodent studies (Dirks and Leeuwenburgh 2006).…”

Section: Introductionmentioning

confidence: 98%

Why calorie restriction would work for human longevity

2006

Biogerontology

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Experimentally imposed calorie restriction (CR) is shown to result in the most reproducible endpoint of lifespan extension in all animals models tested. In this presentation, the question of CR's effect on human longevity is reviewed by discussing data pertinent to the putative efficacy of CR on humans. Arguments are presented in support of this possibility based on CR's unique abilities to retard biological functional declines and to deter pathological processes, both of which are major targets of deleterious oxidative stress. To delineate the cellular and molecular mechanisms of CR's efficacy on human longevity, this review elaborates on the modulation of CR on the inflammatory process, a common risk factor for many chronic diseases. Discussions also include evidence from human data on the effect of CR in the loss of body weight, known to suppress inflammatory cytokines, subsequently leading to the reduction of chronic diseases known to compromise the functional longevity of humans.

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