New Horizons: Dietary protein, ageing and the Okinawan ratio.

Nutrition has profound effects on ageing and lifespan. Caloric restriction is the major nutritional intervention that historically has been shown to influence lifespan and/or healthspan in many animal models. Studies have suggested that a reduction in protein intake can also increase lifespan, albeit not as dramatically as caloric restriction. More recent research based on nutritional geometry has attempted to define the effects of nutrition on ageing over a broad landscape of dietary macronutrients and energy content. Such studies in insects and mice indicate that animals with ad libitum access to low-protein, high-carbohydrate diets have longest lifespans. Remarkably, the optimum content and ratio of dietary protein to carbohydrates for ageing in experimental animals are almost identical to those in the traditional diets of the long-lived people on the island of Okinawa.

[1]  Foreman,et al.  The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. , 2013, JAMA.

[2]  T. Mckeown The Role of Medicine , 1979 .

[3]  L. Partridge,et al.  Promoting Health and Longevity through Diet: From Model Organisms to Humans , 2015, Cell.

[4]  R. de Cabo,et al.  The evolution of research on ageing and nutrition. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  S. Klein,et al.  Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Richard G Melvin,et al.  The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. , 2014, Cell metabolism.

[7]  R. Wolfe,et al.  Is the optimal level of protein intake for older adults greater than the recommended dietary allowance? , 2013, The journals of gerontology. Series A, Biological sciences and medical sciences.

[8]  D. Willcox,et al.  The Okinawan Diet: Health Implications of a Low-Calorie, Nutrient-Dense, Antioxidant-Rich Dietary Pattern Low in Glycemic Load , 2009, Journal of the American College of Nutrition.

[9]  R. de Cabo,et al.  Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice. , 2015, Cell reports.

[10]  K. Yano,et al.  Caloric Restriction, the Traditional Okinawan Diet, and Healthy Aging , 2007, Annals of the New York Academy of Sciences.

[11]  S. Simpson,et al.  Obesity: the protein leverage hypothesis , 2005, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[12]  O. Witte,et al.  Branched-chain amino acid catabolism is a conserved regulator of physiological ageing , 2015, Nature Communications.

[13]  R. Wolfe,et al.  Optimal protein intake in the elderly. , 2008, Clinical nutrition.

[14]  M. Levine,et al.  Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. , 2014, Cell metabolism.

[15]  J. Powles,et al.  Food, livestock production, energy, climate change, and health , 2007, The Lancet.

[16]  L. Redman,et al.  Effect of Two‐Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non‐Obese Younger Adults: A Randomized Clinical Trial , 2016, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  D. Willcox,et al.  Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: controversies and clinical implications , 2013, Current opinion in clinical nutrition and metabolic care.

[18]  T. Kirkwood,et al.  Food restriction, evolution and ageing , 2005, Mechanisms of Ageing and Development.

[19]  J. Baur,et al.  Are sirtuins viable targets for improving healthspan and lifespan? , 2012, Nature Reviews Drug Discovery.

[20]  M. Westerterp-Plantenga,et al.  Food Intake in the Daily Environment After Energy-reduced Lunch, Related to Habitual Meal Frequency , 1994, Appetite.

[21]  S. Simpson,et al.  Perspective: Tricks of the trade , 2014, Nature.

[22]  R. de Cabo,et al.  Macronutrients and caloric intake in health and longevity. , 2015, The Journal of endocrinology.

[23]  V. Longo,et al.  Protein and amino acid restriction, aging and disease: from yeast to humans , 2014, Trends in Endocrinology & Metabolism.

[24]  E. Mercken,et al.  Of mice and men: The benefits of caloric restriction, exercise, and mimetics , 2012, Ageing Research Reviews.

[25]  David Raubenheimer,et al.  Putting the Balance Back in Diet , 2015, Cell.

[26]  H. Daniel,et al.  Branched-chain amino acids as biomarkers in diabetes. , 2016, Current opinion in clinical nutrition and metabolic care.

[27]  R. Wolfe Update on protein intake: importance of milk proteins for health status of the elderly. , 2015, Nutrition reviews.

[28]  Shinichi Nakagawa,et al.  Comparative and meta‐analytic insights into life extension via dietary restriction , 2012, Aging cell.

[29]  C M McCay,et al.  The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. , 1935, Nutrition.

[30]  E. Masoro,et al.  Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics. , 1985, Journal of gerontology.

[31]  G. D’Antona,et al.  Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. , 2010, Cell metabolism.

[32]  J P Bunker,et al.  The role of medical care in contributing to health improvements within societies. , 2001, International journal of epidemiology.

[33]  R. Pamplona,et al.  Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection. , 2006, Biochimica et biophysica acta.

[34]  B. Rasmussen,et al.  Dietary protein recommendations and the prevention of sarcopenia , 2009, Current opinion in clinical nutrition and metabolic care.

[35]  Corby K. Martin,et al.  A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. , 2015, The journals of gerontology. Series A, Biological sciences and medical sciences.

[36]  Marion Nestle,et al.  Food Politics , 2002 .

[37]  Richard G Melvin,et al.  The Influence of Macronutrients on Splanchnic and Hepatic Lymphocytes in Aging Mice. , 2015, The journals of gerontology. Series A, Biological sciences and medical sciences.

[38]  David Raubenheimer,et al.  Lifespan and reproduction in Drosophila: New insights from nutritional geometry , 2008, Proceedings of the National Academy of Sciences.

[39]  Corby K. Martin,et al.  The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. , 2011, Contemporary clinical trials.

[40]  E. Børsheim,et al.  Health effects of protein intake in healthy adults: a systematic literature review , 2013, Food & nutrition research.

[41]  Rod D. Roscoe,et al.  Genetic determinants of exceptional human longevity: insights from the Okinawa Centenarian Study , 2006, AGE.

[42]  D. Tilman,et al.  Global diets link environmental sustainability and human health , 2014, Nature.

[43]  R. de Cabo,et al.  The impact of low-protein high-carbohydrate diets on aging and lifespan , 2015, Cellular and Molecular Life Sciences.