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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 [1] 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.





[1]  Cell Reports 14, 1–7 January 26, 2016

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


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.
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  • 6 months later...

A new paper published in July by Luigi Fontana:

Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

Published: 07/13/16


Full paper


@Dean: fell free to move it to another topic if you think it should not be there.



Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.



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