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All, In case you missed it, Al posted a pointer to a new review paper  by Luigi that reviews lots of interesting human CR results, including Okinawans, Biosphere II, Minnesota Starvation Study, CALERIE-I and II, and our own CR Society Cohort study. I read through it and didn't see anything particularly new. Pretty much a thorough review of everything we already know about human CR, much of it from his own work. Most of the positive evidence for CR benefits in humans comes from us. Reading between the lines, and looking at the lack of many expected changes, the CALERIE studies were somewhat of a disappointment. For anyone who is steeped in CR science, it probably isn't worth reading, except perhaps as a refresher. But for newcomers to CR, it looks to be a very good introduction. --Dean --------  Ageing Res Rev. 2016 Aug 17. pii: S1568-1637(16)30183-0. doi: 10.1016/j.arr.2016.08.005. [Epub ahead of print] Review. Calorie restriction in humans: An update. Most J, Tosti V, Redman LM, Fontana L. Full text: http://sci-hub.cc/10...arr.2016.08.005 Abstract Calorie restriction (CR), a nutritional intervention of reduced energy intake but with adequate nutrition, has been shown to extend healthspan and lifespan in rodent and primate models. Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity. In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality. In this paper, we will discuss the effects of CR in non-obese humans on these physiological parameters. Special emphasis is committed to recent clinical intervention trials that have investigated the feasibility and effects of CR in young and middle-aged men and women on parameters of energy metabolism and metabolic risk factors of age-associated disease in great detail. Additionally, data from individuals who are either naturally exposed to CR or those who are self-practicing this dietary intervention allows us to speculate on longer-term effects of more severe CR in humans. PMID: 27544442
All, Over on this thread, Cloud did a helpful translation of a talk (in Italian) by everyone's favorite CR researcher, Luigi Fontana. In his talk, Luigi mentions a new paper  he and colleagues published this month in the open access journal Cell Reports (full text). It looks at several important biomarkers in some of us from the CR Society (mean BMI 19.2), as compared with endurance athletes (mean BMI 22.4) and normal weight controls (mean BMI 25.2). The CR group has significantly higher cortisol (15.6 ng/dl) than either the athletes (11.2) or the controls (12.3). The authors suggest this could be a good thing, since it may reduce systemic inflammation, and is consistent with elevated corticosteroids in CRed rodents. They didn't report any comparison of inflammation markers directly, but did show that one marker of inflammation, tumor necrosis factor alpha (TNF-a), was inversely correlated with cortisol levels across all subjects. This suggest to me that the change in TNF-a (or other markers of inflammation) probably wasn't significantly different across groups, or they would have reported it directly. Unfortunately, the rest of the paper only compares the CR group with the controls - they apparently didn't perform muscle biopsies on the athletes. Compared with controls, the CR folks had higher levels of stress-related biomarkers, like several heat shock proteins (HSPs), and markers of upregulated autophagy, "involved in cellular protein quality control and removal of dysfunctional proteins and organelles." Here is their conclusion: These CR-induced hormetic responses may play a key role in preserving protein quality control, preventing age-associated proteotoxicity, and increasing the capacity for degrading dysfunctional proteins and organelles, thereby preserving cell functionality and the capacity to adjust to a changing environment. These vital housekeeping homeostatic processes have been shown to protect against age-associated disease and may be involved in slowing the rate of aging in humans. Luigi & co. seem to be big into the health/longevity benefits of hormesis lately, including CR, intermittent fasting, exercise, and keeping abdominal fat low. See this thread for more on Luigi's current perspective, from Cloud's translated highlights from Luigi's recent talk. --Dean -------------  Cell Reports 14, 1–7 January 26, 2016 http://dx.doi.org/10.1016/j.celrep.2015.12.042 Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle Ling Yang,1,11 Danilo Licastro,2,11 Edda Cava,3,4,11 Nicola Veronese,3,5 Francesco Spelta,3,6 Wanda Rizza,3,7 Beatrice Bertozzi,3 Dennis T. Villareal,3,8 Go¨ khan S. Hotamisligil,1 John O. Holloszy,3 and Luigi Fontana Full text: http://www.cell.com/cell-reports/pdf/S2211-1247(15)01483-7.pdf SUMMARY Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3–15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p % 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles.