Researcher Jon Ramsey, PhD is Professor in the Department of Molecular Biosciences within the School of Veterinary Medicine at UC Davis. His study of animals focuses on nutrition as it relates to obesity and aging. The goal of his research is to understand the biological mechanisms that contribute to the aging process and to develop dietary interventions that promote healthy aging and weight loss.

In this podcast, NBT Scientific Director Megan Roberts interviews Dr. Ramsey about his research in the area of calorie restriction and its beneficial effects on longevity and healthspan. They examine the scientific literature on energy and macronutrient restriction, including some of the possible biological mechanisms driving the anti-aging effects of these interventions. They also discuss what this all means in practical terms for those seeking optimal health as they age.

Here’s the outline of this interview with Jon Ramsey:

[00:01:35] Calorie restriction for increasing lifespan.

[00:02:01] Theories of aging.

[00:04:40] Osborne and Mendel; Study: Osborne, Thomas B., Lafayette B. Mendel, and Edna L. Ferry. "The effect of retardation of growth upon the breeding period and duration of life of rats." Science 45.1160 (1917): 294-295.

[00:04:58] Clive McCay; Studies: McCay, Clive Maine, and Mary F. Crowell. "Prolonging the life span." The Scientific Monthly 39.5 (1934): 405-414 and McCay, Carl M., Mary F. Crowell, and Lewis A. Maynard. "The effect of retarded growth upon the length of life span and upon the ultimate body size: one figure." The journal of Nutrition 10.1 (1935): 63-79.

[00:06:25] Calorie restriction literature in animals.

[00:07:39] Types of rodents studied.

[00:08:09] Comparing effect of caloric restriction (CR) on different strains of mice; Study: Liao, Chen‐Yu, et al. "Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening." Aging cell 9.1 (2010): 92-95.

[00:09:08] Time restricted feeding in animal models.

[00:11:51] Calorie restriction vs. malnutrition.

[00:12:00] Different levels of calorie restriction. Study: Weindruch, Richard, et al. "The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake." The Journal of nutrition 116.4 (1986): 641-654.

[00:13:36] Effects of 10% dietary restriction: Richardson, Arlan, et al. "Significant life extension by ten percent dietary restriction." Annals of the New York Academy of Sciences 1363.1 (2016): 11-17.

[00:15:09] CALERIE study and resulting Publications.

[00:17:56] Analyses of CALERIE data. Studies: Belsky, Daniel W., et al. "Change in the rate of biological aging in response to caloric restriction: CALERIE Biobank Analysis." The Journals of Gerontology: Series A 73.1 (2017): 4-10. and Redman, Leanne M., et al. "Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging." Cell metabolism 27.4 (2018): 805-815.

[00:19:21] Dietary restriction and oxidative stress; Study: Walsh, Michael E., Yun Shi, and Holly Van Remmen. "The effects of dietary restriction on oxidative stress in rodents." Free Radical Biology and Medicine 66 (2014): 88-99.

[00:20:29] Podcast: How Oxidative Stress Impacts Performance and Healthspan, with Megan Roberts.

[00:20:40] Effects of CR on reactive oxidative species production; Study: Ramsey, Jon J., Mary-Ellen Harper, and Richard Weindruch. "Restriction of energy intake, energy expenditure, and aging." Free Radical Biology and Medicine 29.10 (2000): 946-968.

[00:20:59] Effects of fasting on the liver; Study: Salin, Karine, et al. "Decreased mitochondrial metabolic requirements in fasting animals carry an oxidative cost." Functional Ecology (2018).

[00:21:56] Control of food intake: Do animal models accurately reflect human behavior?

[00:25:06] Enriched environment; Study: McMurphy, Travis, et al. "Implementation of environmental enrichment after middle age promotes healthy aging." Aging (Albany NY) 10.7 (2018): 1698.

[00:26:16] Monkey studies; Study: Ramsey, J. J., et al. "Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study." Experimental gerontology 35.9-10 (2000): 1131-1149.

[00:26:35] University of Wisconsin study: Colman, Ricki J., et al. "Caloric restriction delays disease onset and mortality in rhesus monkeys." Science 325.5937 (2009): 201-204.

[00:26:35] National Institute on Aging study: Mattison, Julie A., et al. "Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study." Nature 489.7415 (2012): 318.

[00:31:34] Biological mechanisms behind the beneficial effects of CR.

[00:33:09] Central metabolism sensors.

[00:35:28] Mitochondrial proton leak.

[00:37:41] Study: Bevilacqua, Lisa, et al. "Effects of short-and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production." American Journal of Physiology-Endocrinology and Metabolism 286.5 (2004): E852-E861.

[00:40:59] The influence of dietary fat source; Study: Villalba, José Manuel, et al. "The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice." Biogerontology 16.5 (2015): 655-670.

[00:42:16] Effects of protein restriction on longevity; Studies: 1. Davis, Teresa A., Connie W. Bales, and Roy E. Beauchene. "Differential effects of dietary caloric and protein restriction in the aging rat." Experimental gerontology 18.6 (1983): 427-435; 2. Pugh, Thomas D., Roger G. Klopp, and Richard Weindruch. "Controlling caloric consumption: protocols for rodents and rhesus monkeys☆." Neurobiology of aging 20.2 (1999): 157-165.

[00:42:23] More recent studies on protein restriction: 1. Pamplona, Reinald, and Gustavo Barja. "Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection." Biochimica Et Biophysica Acta (BBA)-Bioenergetics 1757.5-6 (2006): 496-508; 2. Caro, Pilar, et al. "Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver." Biogerontology 10.5 (2009): 579-592.

[00:43:42] Morris Ross study: Ross, Morris H. "Length of life and nutrition in the rat." The Journal of nutrition 75.2 (1961): 197-210.

[00:44:03] Effects of dietary lipid composition on lifespan; Study: López-Domínguez, José A., et al. "The influence of dietary fat source on life span in calorie restricted mice." Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences 70.10 (2014): 1181-1188.

[00:45:07] Anthony J. Hulbert.

[00:48:46] Omega-3 study: Aung, Theingi, et al. "Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals." JAMA cardiology 3.3 (2018): 225-234.

[00:50:02] Ketogenic Diets.

[00:50:05] Study: Roberts, Megan N., et al. "A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice." Cell Metabolism 26.3 (2017): 539-546. Podcast: A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice, with Megan (Hall) Roberts.

[00:53:47] Intermittent fasting study: Mitchell, Sarah J., et al. "Daily fasting improves health and survival in male mice independent of diet composition and calories." Cell metabolism(2018).

[00:54:19] Valter Longo, PhD.

[00:54:49] Weight cycling; Study: Smith Jr, Daniel L., et al. "Weight cycling increases longevity compared with sustained obesity in mice." Obesity 26.11 (2018): 1733-1739.

[00:55:22] Exercise in the context of carb restriction and longevity.

[00:56:08] Study: Holloszy, John O., et al. "Effect of voluntary exercise on longevity of rats." Journal of applied physiology 59.3 (1985): 826-831.

[00:58:41] Take home points.

[01:01:08] With unlimited resources, what would you study?

[01:02:08] Jon Ramsey, PhD at UC Davis.