Associations of antioxidant nutrients and oxidative DNA damage in healthy African-American and white adults. 2015. Future research is required to understand whether these findings translate to humans. Davinelli S, Willcox DC, Scapagnini G. 2012. TRF is a type of intermittent fasting in which all calories are consumed within a consistent time window, usually between 6 and 12 waking hours of a day (95, 129). The Biosphere-II experiment provided an unexpected, involuntary opportunity to observe CR in humans. Body fat distribution with long-term dietary restriction in adult male rhesus macaques. Similar to the Phase 1 CR through dietary intervention alone, the majority (69%) of the weight loss consisted of FM; however, a loss of FFM (4.0 0.3%) was also observed (103). A low-glycemic load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE trial. The most-recognized metabolic difference between African Americans and Caucasians is the difference in metabolic rate. Participants would weigh themselves daily, plot the weight on their personal nomogram, and receive weekly coaching to understand that more or less weight loss could be achieved by modifications to calorie intake. Bowers J, Terrien J, Clerget-Froidevaux MS, Gothie JD, Rozing MP, et al. For nonhuman primates and humans, diets with prescriptions ranging from 10% to 30% CR have shown beneficial effects on biomarkers of aging and health span. In controlled preclinical studies using various animal models, CR has extended life span by 50300% (43). Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity. The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly, The calorically restricted low-fat nutrient-dense diet in Biosphere-2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Larson-Meyer DE, Heilbronn LK, Redman LM, Newcomer BR, Frisard MI, et al. Limited evidence suggests greater preservation of FFM with intermittent fasting due to changes in gene expression and enzymatic activity associated with mitochondrial biogenesis and autophagy with fasting (2, 87). Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys. Interestingly, the reduction in core temperature reflected a reduction in body temperature at night only (105). Wegman MP, Guo MH, Bennion DM, Shankar MN, Chrzanowski SM, et al. In elderly persons, the combination of exercise training and increased protein intake promotes greater improvements in muscle mass and strength than either approach alone (77). 2017. Such disparities in health and aging may be related to socioeconomic, environmental, and behavioral factors, including low physical activity and smoking, which are more prevalent in African Americans (149), but significant differences in metabolic pathways may contribute to the increased mortality of African Americans. (a) Aging in a hypercaloric environment presents many physiological stressors, resulting in unhealthy aging. You May Live Longer By Severely Restricting Calories, Scientis The mechanism or In one of the 6-month pilot trials, declines in core body temperature occurred in both CR (0.2 0.05C) and CR+Ex (0.3 0.08C) participants. Evidence from observational, preclinical, and clinical trials suggests the ability to increase life span by 15 years with an improvement in health span and quality of life. WebCALORIE RESTRICTION. 2011. Finally, compared with CR animals, ad libitumfed animals had double the rate and more severe cases of age-associated diseases, including diabetes, cancer, cardiovascular disease, and osteoporosis (81). Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the worlds longest-lived people and its potential impact on morbidity and life span. The 6-month pilot study at the Pennington Biomedical Research Center compared 25% CR achieved through (a) diet restriction alone and (b) a combination of dietary restriction (12.5%) and exercise-induced energy expenditure (12.5%) (CR+Ex) with an ad libitum control group (AL) (42). Preclinical studies suggest that intermittent fasting regimes stimulate protective cellular mechanisms observed with CR, such as autophagy, mitochondrial efficiency, reduced ROS production, and declines in inflammatory cytokines (1). Figure 1: The myriad effects of caloric restriction (CR). With advancing age (>65 years), this J-shaped BMImortality curve is right-shifted (lowest risk, 2728 kg/m2) (151); thus, reducing body weight (to BMI <27 kg/m2) through CR may be associated with an increased mortality risk. Confirming the hypothesis was the finding that mass-adjusted sleeping energy expenditure was reduced after 6 months of CR and CR+Ex, indicating metabolic adaptation and perhaps a slowing of primary aging (Figure 2) (42). Energy expenditure and substrate oxidation in White and African American young adults without obesity. 2008. More than 100 theories exist to explain the mechanisms of the aging process, but many can be consolidated into two prevailing theories. 2019. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. Finally, it may be necessary to consider the population (e.g., young, obese, elderly) and length of prescription (long versus short term) when determining the optimal dose of CR. All diets varied between 20% and 35% fat, 15% and 30% protein, and 40% and 60% carbohydrate and provided a fiber ratio of 14 g/1,000 kcal. The innate progression of aging is defined as primary aging (Figure 1). Damage to these components impairs their function and requires increased energy for repair, breakdown, resynthesis, or elimination and increases oxidative stress, for instance, by activation of the uncoupled protein response (107). After 1 year, CR produced improvements in left ventricular function in healthy older adults, a benefit typically observed with exercise (109). Increased activation of protein chaperones, in particular a 1.8-fold increase in heat shock protein 70, along with increased regulation of several autophagy genes, was also evident in comparison to matched controls (153). 2019. McKiernan SH, Colman RJ, Aiken E, Evans TD, Beasley TM, et al. The publisher's final edited version of this article is available at, calorie restriction, aging, CALERIE, metabolic adaptation, intermittent fasting, Fasting or caloric restriction for healthy aging. Mortality as an adverse outcome of sarcopenia. During the 6-month pilot at Pennington Biomedical, participants in both CR groups achieved 10% weight loss (42) with a 25% reduction in total FM and a 27% reduction in visceral fat (104), the depot that is most closely related to metabolic diseases (17). A recent trial investigated the effect of aerobic, resistance, or combined resistance and aerobic exercise training during 6 months of CR with 1 g/kg/day protein intake in older, obese adults; it showed that the combination of aerobic and resistance training improved myocellular quality and muscle protein synthesis and preserved muscle mass (22). 2016. The CALERIE studies reported in the media have been critiqued for their generalized reports suggesting self-implementation of moderate to severe CR to improve life span (65). 2004. Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones. This transition to fatty acids and fatty acidderived ketones, known as the metabolic switch, may be responsible for many of the underlying health adaptations to intermittent fasting. Colleluori G, Aguirre L, Phadnis U, Fowler K, Armamento-Villareal R, et al. Purportedly, a more tolerable approach to ADF is modified ADF, in which a small percentage of calories (i.e., ~25% of daily caloric needs) is permitted on fasting days while ad libitum eating continues on alternative days. 2013. The molecular, cellular, tissue-level, and organ-level changes that are affected by these stressors and cause a decline in physiological function have been described as overlapping sets of 510 processes (72). Notably the reductions in bone mineral density in CALERIE persisted despite the provision of a multivitamin and mineral supplement (and additional calcium), suggesting that adaptations to bone metabolism expand beyond micronutrient availability. 2019. To date, studies of TRF have been relatively short in duration (days to less than 9 weeks) and have involved very few subjects. Three 9-day diets were provided in a 3-day rotating menu. Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. An emerging concern regarding CR in elderly individuals is sarcopenia, which is a major cause of immobility, frailty, and mortality (54, 93). More research is required to discern the genetic, environmental, lifestyle, and metabolic factors that cause the distinct differences in hallmarks of aging between African Americans and whites. Caloric restriction may reverse age-related autonomic decline in humans. Das SK, Roberts SB, Bhapkar MV, Villareal DT, Fontana L, et al. 2016. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms, Muscle fiber specific apoptosis and TNF- signaling in sarcopenia are attenuated by life-long calorie restriction. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Initiated by the late Roy Walford, a Biosphere-II participant, CR Society International is a group of free-living individuals who have voluntarily restricted their energy intake for 3 to 15 years. 2016. 2013. WebThe diet known as calorie restriction (CR) is the most reproducible way to extend the lifespan of mammals. Aerobic plus resistance exercise in obese older adults improves muscle protein synthesis and preserves myocellular quality despite weight loss. Aging describes the decline in physical and physiological functioning of living organisms. In this population, the RDA for protein is 0.8 g/kg/day (26); protein intake below 1 g/kg/day negatively affects muscle strength (40, 84), while intake above 1.2 g/kg/day may be optimal for skeletal muscle health with advancing age (9). Yet, the penultimate study to test the effects of CR on life span in a controlled clinical setting is impractical, and may never be performed. However, the degree of weight loss was influenced by the glycemic load of the diet and baseline insulin secretion; individuals with higher insulin secretion lost more weight on a low-glycemic diet than on a high-glycemic diet (99, 100). The Panacea of Human Aging: Calorie Restriction Versus Exercise 8600 Rockville Pike Also, quality of sleep and sexual function were not affected or even improved (sexual drive and relationships). Improved mitochondrial energy efficiency occurs when mitochondrial respiration is closely coupled to ATP production and electron leakage is decreased. Calorie restriction and fasting diets: What do we know? Epigenetic changes involve alterations in DNA methylation patterns, posttranslational modification of histones, and chromatin remodeling. It is thought that eating during a restricted time interval brings metabolic processes in concert with circadian rhythms, allowing anticipatory and acute metabolic responses to synergistically maintain nutrient homeostasis (19). 2005. Mitochondrial respiration is associated with lower energy expenditure and lower aerobic capacity in African American women. Long-term caloric restriction ameliorates the decline in diastolic function in humans. The seven pillars of aging include adaptation to stress, inflammation, metabolism, macromolecular damage, proteostasis, epigenetic modification, and stem cells and regeneration. The 40% CR led to severe adverse effects, both physical (e.g., chronic weakness, reduced aerobic capacity, and painful lower limb edema) and psychological (e.g., emotional distress, confusion, apathy, depression, hysteria, hypochondriasis, suicidal thoughts, and loss of sex drive), which emerged after 6 weeks (59). Can Calorie Restriction Extend Your Lifespan - Science NIA-supported studies suggest that calorie restriction may improve immune function and reduce chronic inflammation, as well as diminish risk factors for heart 2000. 2007. and transmitted securely. 2018. Furthermore, data that would shed light on primary and secondary aging or the molecular mechanisms from the standpoint of the seven pillars of aging have not been reported. As with most behavior-based interventions, compliance wavers over time. The future research agenda of the National Institutes of Health (NIH) described the need for long-term CR interventions (i.e., 5 years) to evaluate long-term sustainability and the attenuation or amplification of biological aging (92). As depicted in Figure 1, the minimal slope allows the human life span to reach approximately 120 years. 2016. However, exciting research in preclinical models suggests that CR may have a positive impact on the underlying molecular mechanisms of developing sarcopenia (23, 83). 1999. These nonhuman primate studies provide exciting data regarding the potential for sustained CR to keep age-associated diseases at bay while preserving physical functionality. Unlike chronological aging, which advances at the same rate in everyone, biological aging refers to the gradual and progressive decline in the integrity of the bodys systems and therefore can be widely variable. 2013. Considering the rate of living and oxidative damage theories of aging, these findings suggest lower rates of primary aging in African Americans and thus cannot explain their lower life expectancy compared with that of whites. The Effect of calorie restriction with or without exercise on insulin sensitivity, -cell function, fat cell size, and ectopic lipid in overweight subjects. Over approximately 9 years, CALERIE comprised three pilot studies (CALERIE 1) followed by a large multisite randomized study (CALERIE 2). Belsky DW, Huffman KM, Pieper CF, Shalev I, Kraus WE. Use of modern technology has shown that methylation patterns are strongly associated with mammalian aging and alone can approximate biological age to within 1.9 years (47). Martin CK, Bhapkar M, Pittas AG, Pieper CF, Das SK, et al. Importantly, the 2-year trial showed that improvements in cardiometabolic health biomarkers were robust even after controlling for weight loss (88). Winter JE, MacInnis RJ, Wattanapenpaiboon N, Nowson CA. With the reduction in FFM, aerobic fitness was unaffected by CR in the younger cohort (64) but declined in the older cohort (141). 2010. (59), which is often discussed in the context of human CR, demonstrated that CR can likely be overprescribed. Effect of two-year caloric restriction on bone metabolism and bone mineral density in non-obese younger adults: a randomized clinical trial. sharing sensitive information, make sure youre on a federal Part 2. Therefore, a proper comparison against traditional, sustained CR is not yet possible. At age 50, weighing and exercising 2009. Stem cell exhaustion limits production of adaptive immune cells, hematopoietic cells, and myocytes. A TRF intervention in prediabetic individuals found improvements in -cell function, insulin sensitivity, oxidative stress, and blood pressure, independent of weight loss (123). With advancing age, greater muscle mass is associated with better physical function and a lower risk of immobility. The CALERIE 2 intervention aimed to reduce caloric intake without enforcing a set nutrient composition and required only that the self-selected diets meet daily Life and death: metabolic rate, membrane composition, and life span of animals. 2006. Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, et al. 2019. Life span is dictated by the process of aging. 2012. With the use of a frequently sampled intravenous glucose tolerance test, 25% CR and CR+Ex led to a 40% and 37% increase, respectively, in insulin sensitivity after 6 months (63). 2017. The lack of persistent slowing of metabolic rate in the longer-duration trial was likely confounded by adherence (~15% during the first 12 months, ~9% during the next 12 months) (103). Since the weight loss trajectory of Phase 1 was modeled for Phase 2, it is not surprising that participants in the multisite trial also evidenced a 10% weight loss at 6, 12, and/or 24 months. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. Moreover, individuals self-practicing CR demonstrated significant improvements in the circulatory system, with a 40% lower carotid intima media thickness (37, 85) and a left ventricular elasticity that was comparable to that of individuals 16 years younger (46). 2006. 2006. Together, these findings regarding the anti-inflammatory benefits of CR are realized only after longer periods (61). Abbreviations: ADF, alternate-day fasting; BMI, body mass index; CR, calorie restriction; mADF, modified ADF; TRF, time-restricted feeding. At this point, research on intermittent fasting remains limited, and randomized controlled trials incorporating various strategies and populations are needed before therapeutic interventions can be prescribed. 2018. Determinants of energy expenditure and fuel utilization in man: effects of body composition, age, sex, ethnicity and glucose tolerance in 916 subjects. 2017. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. (10) calculated the change in biological age across the 24-month trial using two different validated equations. Mechanistically, the rate of living theory is supported by the free radical theory of aging (41), which postulates that 13% of oxygen consumed by mitochondrial ATP production generates reactive oxygen species (ROS), that is, oxidative stress. Intermittent fasting is a broad term used to describe a variety of eating patterns in which food consumption occurs during a restricted time period in order to extend the length of time spent fasting. Toward a unified theory of caloric restriction and longevity It is important to note that effects from TRF may differ according to the time of day that the feeding window occurs, with early feedings superior to late feedings (123). CR is the most prominent and well-researched intervention with the intent to attenuate mammalian aging. Fontana L, Meyer TE, Klein S, Holloszy JO. Larson-Meyer DE, Redman L, Heilbronn LK, Martin CK, Ravussin E. 2010. While the extent of FM loss was similar between males and females, sex had a significant effect on FFM loss: Males evidenced greater declines than females (29). Mammalian mitochondria and aging: an update. Unlike continuous CR, TRF may preserve resting energy expenditure, which negates positive impacts on primary aging yet may be superior for protection against secondary aging. Similar findings were observed for resting metabolic rate measured in CALERIE 2, but metabolic adaptation was significantly different from the ad libitumeating group only after 12 months (103). Effects of two years of calorie restriction on aerobic capacity and muscle strength. The CALERIE 2 intervention aimed to reduce caloric intake without enforcing a set nutrient composition and required only that the self-selected diets meet daily micronutrient requirements. Briefly, oxidative stress, or the accumulation of damaging free oxygen radicals, is a crucial signal in cells and tissues that induces pathways to restore homeostasis in a challenged system (110). High core body temperature is associated with increased metabolic rate and, therefore, is believed to reflect accelerated primary aging. Toledo FGS, Dube JJ, Goodpaster BH, Stefanovic-Racic M, Coen PM, DeLany JP. Fontana L, Shew JL, Holloszy JO, Villareal DT. 2000. Weiss EP, Villareal DT, Racette SB, Steger-May K, Premachandra BN, et al. Although evidence suggests that long-term CR effectively slows cellular mechanisms of primary aging and increases health span in the third to fifth decades of life, ensuring that it does not also adversely affect the risk for sarcopenia and all-cause mortality in later aging (sixth decade of life and beyond) is imperative for assessing its overall impact on human health. Preclinical studies in rodents provide valuable insights into potential mechanisms underpinning the beneficial effect of CR on humans. The https:// ensures that you are connecting to the Nevertheless, despite the numerous beneficial effects of CR, described above, sustained CR can have potential drawbacks, such as difficulty of maintaining compliance and adverse effects on mental health through weight lossinduced hunger and the loss of FFM. 2007. An acceleration of this process reflects the interaction between innate aging and the extrinsic influences of the environment. Whether this protective effect of higher protein intake translates to elderly individuals undergoing CR with or without exercise has yet to be determined. Introduction Research on the biology of ageing has been conducted for centuries. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.
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