CALORIE RESTRICTION MIMETICS
An Introduction to Calorie Restriction
A quest of modern medical practice is to promote longevity (long life in good health). Anti-aging medicine is oversubscribed with “band-aid” approaches in the relentless pursuit of the elusive “fountain of youth.” That being said, the only intervention that has been shown unequivocally to extend average and maximal lifespan, in a wide variety of living organisms, is the restriction of calorie intake. While genetic manipulations could enhance lifespan, modern science has a long way to go before this futuristic intervention can be applied. There are thousands of published articles, over a seventy year period, that focus on the ability of significant reductions in calorie intake to exert their effects on enhancing lifespan and reducing the incidence and prevalence of age- related diseases. Much of this literature refers to animal models of aging. It appears that the application of calorie restriction of the order of 30-50% (up to 70%) below average free-feeding calorie intake may induce an inhibitory effect on many aspects of aging, including aging processes in non-human species, primates and most probably humans. A precise definition of the required level of calorie restriction to promote longevity is not possible, especially in these days of much “social gluttony". About a 30-40% reduction below a 2000Kcal intake in humans may suffice to promote longevity (“a hard act to follow”). Many people ingest 3-6,000 calories per day which may require about a 50-70% reduction in intake. Much research has been performed on calorie restriction in rodents, but it appears that biological responses to calorie restriction are quite similar in primates and many other species, including humankind. However, one could anticipate intraindividual and interindividual responses to different levels of reductions in daily calorie intake and episodic fasting has not been studied in detail.
Despite isolated arguments to the contrary, it seems that calorie restriction is an effective-longevity promoting strategy for humans, but the widespread application of the degree of dietary restriction required to retard aging creates potential compliance problems of an insurmountable magnitude. It is a formidable task to change the eating habits of a nation, but the North American continent has a recalcitrant problem with “food-portion-size distortion”, resulting in excessive calorie intake. This issue is a pivotal component of the “obesity epidemic” in North America, and elsewhere. Emerging nations are now at great risk. There are many proponents of the use of food restriction strategies for anti-aging. The first observations of the lifespan enhancing ability of calorie-restriction were made more than 70 years ago. These observations lay somewhat dormant in the medical literature, until the 1950s, when the pioneer of modern calorie restriction interventions, Professor Roy Walford started to popularize his concepts of the “120 Year Old Diet”. In brief, Walford discussed the advantage of the “high/low diet”, where he suggested a combination of “under-nutrition without malnutrition for health and longevity".
The proposals of Professor Walford involved the careful application of a calorie restricted diet that was “nutrient dense”. Nutrient density implies the provision of vital and essential nutritional cofactors, most notably vitamins and minerals with phytonutrients. Thus, popping a standard “multivitamin” pill is not a comprehensive or adequate intervention to provide nutrient density in a calorie restricted diet. Interests in calorie restriction have accelerated to a point where this approach has generated great interest as a research focus for the US National Institutes of Aging. Recent research has expanded beyond laboratory animals to human interventions using dietary calorie restriction or substances that can mimic the biological changes that are seen in the presence of significant reductions of daily calorie intake (so-called “Calorie Restriction Mimetics”). Conservative scientists demand to see more research into the human effects of calorie restriction as an anti-aging strategy, but it seems prudent to accept this intervention as a valid, reliable and safe approach to enhancing lifespan. Governments of industrialized societies have made recent calls to lower calorie intake in the diets, while the food industry continues to peddle calorie excess, especially with cheap calories such as high fructose corn syrup and saturated or even hydrogenated fats.
The Concept of the Calorie Restriction Mimetic
As experimental studies started to define the beneficial biochemical and physiological outcomes of calorie restriction, scientists started to propose that there were a variety of substances (drugs and natural compounds) that could mimic these desirable effects on body structures and functions. In the late 1990’s scientists started to propose the notion that there were “calorie restriction mimetics” (CRM) that have putative antiaging properties. These proposals incorporated notions that some compounds could prolong life, as a result of their ability to induce some of the biological changes that occur as a consequence of direct reductions of overall calorie intake. Many experiments involving reduction of total calorie intake have shown that calorie restriction improves a number of biomarkers of aging, with overt evidence of improved general health. The use of calorie restriction mimetics, in isolation of significant dietary calorie reduction, has the naïve appeal to some of providing an “easy option” for longevity promotion. The popularity of fad diets is driven by the “easy way out” mentality. However, it seems quite reasonable to conclude that the combined use of calorie restriction mimetics, with tolerable reductions of overall calorie intake, would act in a highly synergistic manner (additive together in their benefits) (Appendix C). This approach seems to be deeply-rooted in good scientific agreement, derived from almost eight decades of research on the benefits of dietary or calorie restriction per-se.
An Introduction to Calorie Restriction
A quest of modern medical practice is to promote longevity (long life in good health). Anti-aging medicine is oversubscribed with “band-aid” approaches in the relentless pursuit of the elusive “fountain of youth.” That being said, the only intervention that has been shown unequivocally to extend average and maximal lifespan, in a wide variety of living organisms, is the restriction of calorie intake. While genetic manipulations could enhance lifespan, modern science has a long way to go before this futuristic intervention can be applied. There are thousands of published articles, over a seventy year period, that focus on the ability of significant reductions in calorie intake to exert their effects on enhancing lifespan and reducing the incidence and prevalence of age- related diseases. Much of this literature refers to animal models of aging. It appears that the application of calorie restriction of the order of 30-50% (up to 70%) below average free-feeding calorie intake may induce an inhibitory effect on many aspects of aging, including aging processes in non-human species, primates and most probably humans. A precise definition of the required level of calorie restriction to promote longevity is not possible, especially in these days of much “social gluttony". About a 30-40% reduction below a 2000Kcal intake in humans may suffice to promote longevity (“a hard act to follow”). Many people ingest 3-6,000 calories per day which may require about a 50-70% reduction in intake. Much research has been performed on calorie restriction in rodents, but it appears that biological responses to calorie restriction are quite similar in primates and many other species, including humankind. However, one could anticipate intraindividual and interindividual responses to different levels of reductions in daily calorie intake and episodic fasting has not been studied in detail.
Despite isolated arguments to the contrary, it seems that calorie restriction is an effective-longevity promoting strategy for humans, but the widespread application of the degree of dietary restriction required to retard aging creates potential compliance problems of an insurmountable magnitude. It is a formidable task to change the eating habits of a nation, but the North American continent has a recalcitrant problem with “food-portion-size distortion”, resulting in excessive calorie intake. This issue is a pivotal component of the “obesity epidemic” in North America, and elsewhere. Emerging nations are now at great risk. There are many proponents of the use of food restriction strategies for anti-aging. The first observations of the lifespan enhancing ability of calorie-restriction were made more than 70 years ago. These observations lay somewhat dormant in the medical literature, until the 1950s, when the pioneer of modern calorie restriction interventions, Professor Roy Walford started to popularize his concepts of the “120 Year Old Diet”. In brief, Walford discussed the advantage of the “high/low diet”, where he suggested a combination of “under-nutrition without malnutrition for health and longevity".
The proposals of Professor Walford involved the careful application of a calorie restricted diet that was “nutrient dense”. Nutrient density implies the provision of vital and essential nutritional cofactors, most notably vitamins and minerals with phytonutrients. Thus, popping a standard “multivitamin” pill is not a comprehensive or adequate intervention to provide nutrient density in a calorie restricted diet. Interests in calorie restriction have accelerated to a point where this approach has generated great interest as a research focus for the US National Institutes of Aging. Recent research has expanded beyond laboratory animals to human interventions using dietary calorie restriction or substances that can mimic the biological changes that are seen in the presence of significant reductions of daily calorie intake (so-called “Calorie Restriction Mimetics”). Conservative scientists demand to see more research into the human effects of calorie restriction as an anti-aging strategy, but it seems prudent to accept this intervention as a valid, reliable and safe approach to enhancing lifespan. Governments of industrialized societies have made recent calls to lower calorie intake in the diets, while the food industry continues to peddle calorie excess, especially with cheap calories such as high fructose corn syrup and saturated or even hydrogenated fats.
The Concept of the Calorie Restriction Mimetic
As experimental studies started to define the beneficial biochemical and physiological outcomes of calorie restriction, scientists started to propose that there were a variety of substances (drugs and natural compounds) that could mimic these desirable effects on body structures and functions. In the late 1990’s scientists started to propose the notion that there were “calorie restriction mimetics” (CRM) that have putative antiaging properties. These proposals incorporated notions that some compounds could prolong life, as a result of their ability to induce some of the biological changes that occur as a consequence of direct reductions of overall calorie intake. Many experiments involving reduction of total calorie intake have shown that calorie restriction improves a number of biomarkers of aging, with overt evidence of improved general health. The use of calorie restriction mimetics, in isolation of significant dietary calorie reduction, has the naïve appeal to some of providing an “easy option” for longevity promotion. The popularity of fad diets is driven by the “easy way out” mentality. However, it seems quite reasonable to conclude that the combined use of calorie restriction mimetics, with tolerable reductions of overall calorie intake, would act in a highly synergistic manner (additive together in their benefits) (Appendix C). This approach seems to be deeply-rooted in good scientific agreement, derived from almost eight decades of research on the benefits of dietary or calorie restriction per-se.
