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The email list system is broken.  Posts cannot be searched.  Many of the posts do not make it to the messages I receive individually and via the daily mailings.  Therefore, I am sending this message, comprised of citations papers that seem to be appropriate to the room of the Forum.  I will try to also provide full-text links and a very brief excerpt or within brackets my synopsis of the paper.  I apologize for the fact some papers discuss results of studies on the overweight or obese, but feel that some benefits seen in such subjects bears on a continuum of benefits accrued by CR and provide incentive to folks who are overweight or obese.  Below are today's papers.

 

 

Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice.
Campus P, Maiolati M, Orsini C, Cabib S.
Behav Brain Res. 2016 Aug 6. pii: S0166-4328(16)30505-8. doi: 10.1016/j.bbr.2016.08.014. [Epub ahead of print]
PMID: 27506654
http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0166432816305058
These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning.


The interaction of fasting, caloric restriction, and diet-induced obesity with 17β-estradiol on the expression of KNDy neuropeptides and their receptors in the female mouse.
Yang JA, Yasrebi A, Snyder M, Roepke TA.
Mol Cell Endocrinol. 2016 Aug 6. pii: S0303-7207(16)30298-2. doi: 10.1016/j.mce.2016.08.008. [Epub ahead of print]
PMID: 27507595
http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0303720716302982
[This paper suggests that steroidal environment and energy state negatively regulate KNDy (Kisspeptin/Neurokinin B/Dynorphin) gene which plays an important role in the https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93gonadal_axis]


Effects of dietary supplementation with EPA and/or α-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet.
Huerta AE, Prieto-Hontoria PL, Fernández-Galilea M, Escoté X, Martínez JA, Moreno-Aliaga MJ.
Biofactors. 2016 Aug 10. doi: 10.1002/biof.1317. [Epub ahead of print]
PMID: 27507611
http://sci-hub.cc/doi/10.1002/biof.1317
α-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage.


Association of the TNF-alpha -308 G/A polymorphisms with metabolic responses secondary to a high protein/low carbohydrate versus a standard hypocaloric diet.
De Luis DA, Aller R, Izaola O, Romero E.
Nutr Hosp. 2016 Jun 30;33(3):267. doi: 10.20960/nh.267. Spanish.
PMID: 27513494
[i have no access to this paper's full texts.]
Carriers of -308 GG promoter variant of TNF-alpha gene have a better metabolic response than -308 GA obese with a high protein hypocaloric diet.

Edited by AlPater

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Sure, I realize it is hard to translate things from an animal so different from humans, but they may be well positioned for doing studies such as those in the paper using the genetics that are available for the worms, their short lifespans and minimal expense compared to rodents.

 

Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside Elicits Life-span Extension and Stress Resistance in Caenorhabditis elegans.

Asthana J, Yadav D, Pant A, Yadav AK, Gupta MM, Pandey R.

J Gerontol A Biol Sci Med Sci. 2016 Sep;71(9):1160-8. doi: 10.1093/gerona/glv173. Epub 2015 Oct 3.

PMID: 26433219

http://sci-hub.cc/10.1093/gerona/glv173

phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) … was able to extend life span in C. elegans by more than 39%. … dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis.

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Metabolic Control of Longevity.
López-Otín C, Galluzzi L, Freije JM, Madeo F, Kroemer G.
Cell. 2016 Aug 11;166(4):802-21. doi: 10.1016/j.cell.2016.07.031. Review.
PMID: 27518560
[Dean could not provide the PMID previously when he discussed this paper in https://www.crsociety.org/topic/11802-review-on-whats-known-about-aging-and-what-to-do-about-it/?hl=galluzzi ]

Anti-aging pharmacology: promises and pitfalls.
Vaiserman AM, Lushchak OV, Koliada AK.
Ageing Res Rev. 2016 Aug 11. pii: S1568-1637(16)30182-9. doi: 10.1016/j.arr.2016.08.004. [Epub ahead of print] Review.
PMID: 27524412
http://sci-hub.cc/10.1016/j.arr.2016.08.004

[Table 7 is a pretty good summary of this extensive review.]
anti-aging pharmacology … drug; antioxidant; calorie restriction mimetic; healthspan; lifespan

Caloric Restriction and Aging Bladder Dysfunction.
Chai TC.
J Urol. 2016 Aug 9. pii: S0022-5347(16)30992-2. doi: 10.1016/j.juro.2016.08.013. [Epub ahead of print] No abstract available.
PMID:  27520084
http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0022534716309922
[Host=microbiota interactions may be involved in CR protection from bladder dysfunction, as not in "The pause that refreshes", as is seen in old men.]
THE bladder does 3 things: stores and empties urine,
and protects kidneys against uropathogens. In this
issue of The Journal Ito et al (page 0000) show that
at least 2 of these 3 functions were altered in aged
F344 rats,1 … modulating  host-microbiota  in-
teractions with metformin, a drug used to treat
metabolic syndrome, altered the longevity of
Caenorhabditis elegans.5 Thus, altering host-microbiota
interactions  can  have  broad-ranging  effects,
including slowing the aging process.
1. Preventive Effects of Long-Term Caloric Restriction on Aging Related in Vivo Bladder Dysfunctions and Molecular Biological Changes in the Bladder and Dorsal Root Ganglia in Rats.
Ito H, Kamei J, Aizawa N, Fujita Y, Suzuki M, Fukuhara H, Fujimura T, Kojima T, Homma Y, Kubota Y, Ito M, Andersson KE, Igawa Y.
J Urol. 2016 May 31. pii: S0022-5347(16)30553-5. doi: 10.1016/j.juro.2016.05.104. [Epub ahead of print]
PMID: 27259654
http://sci-hub.cc/10.1016/j.juro.2016.05.104
Male Fischer 344 rats … with food restricted to 3 days per week. … Old rats with free access showed greater post-void residual volume and lower voiding efficiency than old rats with caloric restriction and young rats.

Edited by AlPater

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Caloric restriction selectively reduces the GABAergic phenotype of mouse hypothalamic proopiomelanocortin neurons.

Jarvie BC, King CM, Hughes AR, Dicken MS, Dennison CS, Hentges ST.

J Physiol. 2016 Aug 17. doi: 10.1113/JP273020. [Epub ahead of print]

PMID: 27531218

[ https://en.wikipedia.org/wiki/Gamma-Aminobutyric_acid“is the chief inhibitory neurotransmitter in the mammalian central nervous system.”  The pdf-availed paper seems to  say that CR, distinctly from other stresses, can act to increase or decrease GABA in one particular part of the brain.]

 

http://www.nutraingredients.com/Research/Protein-pacing-helps-weight-loss-and-maintenance-Study

Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

Arciero PJ, Edmonds R, He F, Ward E, Gumpricht E, Mohr A, Ormsbee MJ, Astrup A.

Nutrients. 2016 Jul 30;8(8). pii: E476. doi: 10.3390/nu8080476.

PMID: 27483317

Free Article

http://www.mdpi.com/2072-6643/8/8/476/htm

Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) … compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) … during long-term (52 week) weight maintenance (WM). [despite similar effects during weight loss] subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05)

 

http://www.businessinsider.com.au/best-ways-to-avoid-aging-2016-8

Metabolic Control of Longevity.

López-Otín C, Galluzzi L, Freije JM, Madeo F, Kroemer G.

Cell. 2016 Aug 11;166(4):802-21. doi: 10.1016/j.cell.2016.07.031. Review.

PMID: 27518560

http://www.cell.com/cell/pdf/S0092-8674(16)30981-3.pdf

lifespan-extending maneuvers including caloric restriction impose beneficial pleiotropic effects on metabolism.

 

Partitioning the variance in calorie restriction-induced weight and fat loss in outbred mice.

Vaanholt LM, Lane JE, Garner B, Speakman JR.

Obesity (Silver Spring). 2016 Aug 16. doi: 10.1002/oby.21579. [Epub ahead of print]

PMID:  27527110

Abstract

Heritability was estimated at 0.43 ± 0.12 for CR-induced changes in body mass and 0.24 ± 0.10 for fat mass using mid-parent-offspring regressions. No significant relationships between weight loss in fathers or foster mothers and offspring were observed. Partitioning of phenotypic variance in weight loss using maximum likelihood modeling indicated 19 ± 17% of the variation could be attributed to additive genetic effects, 8 ± 14% to maternal effects during pregnancy, and <1% to maternal effects during lactation. A narrow-sense heritability around 0.50 was observed for ad libitum food intake and general activity.

Caloric restriction selectively reduces the GABAergic phenotype of mouse hypothalamic proopiomelanocortin neurons.

Jarvie BC, King CM, Hughes AR, Dicken MS, Dennison CS, Hentges ST.

J Physiol. 2016 Aug 17. doi: 10.1113/JP273020. [Epub ahead of print]

PMID: 27531218

[ https://en.wikipedia.org/wiki/Gamma-Aminobutyric_acid“is the chief inhibitory neurotransmitter in the mammalian central nervous system.”  The pdf-availed paper seems to  say that CR, distinctly from other stresses, can act to increase or decrease GABA in one particular part of the brain.]

 

http://www.nutraingredients.com/Research/Protein-pacing-helps-weight-loss-and-maintenance-Study

Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

Arciero PJ, Edmonds R, He F, Ward E, Gumpricht E, Mohr A, Ormsbee MJ, Astrup A.

Nutrients. 2016 Jul 30;8(8). pii: E476. doi: 10.3390/nu8080476.

PMID: 27483317

Free Article

http://www.mdpi.com/2072-6643/8/8/476/htm

Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) … compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) … during long-term (52 week) weight maintenance (WM). [despite similar effects during weight loss] subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05)

 

http://www.businessinsider.com.au/best-ways-to-avoid-aging-2016-8

Metabolic Control of Longevity.

López-Otín C, Galluzzi L, Freije JM, Madeo F, Kroemer G.

Cell. 2016 Aug 11;166(4):802-21. doi: 10.1016/j.cell.2016.07.031. Review.

PMID: 27518560

http://www.cell.com/cell/pdf/S0092-8674(16)30981-3.pdf

lifespan-extending maneuvers including caloric restriction impose beneficial pleiotropic effects on metabolism.

 

Partitioning the variance in calorie restriction-induced weight and fat loss in outbred mice.

Vaanholt LM, Lane JE, Garner B, Speakman JR.

Obesity (Silver Spring). 2016 Aug 16. doi: 10.1002/oby.21579. [Epub ahead of print]

PMID:  27527110

Abstract

Heritability was estimated at 0.43 ± 0.12 for CR-induced changes in body mass and 0.24 ± 0.10 for fat mass using mid-parent-offspring regressions. No significant relationships between weight loss in fathers or foster mothers and offspring were observed. Partitioning of phenotypic variance in weight loss using maximum likelihood modeling indicated 19 ± 17% of the variation could be attributed to additive genetic effects, 8 ± 14% to maternal effects during pregnancy, and <1% to maternal effects during lactation. A narrow-sense heritability around 0.50 was observed for ad libitum food intake and general activity.

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Changes in circulating vitamin D levels with loss of adipose tissue.

Gangloff A, Bergeron J, Lemieux I, Després JP.

Curr Opin Clin Nutr Metab Care. 2016 Aug 16. [Epub ahead of print]

PMID: 27537278

REVIEW … Improvements of circulating 25(OH)D levels with adiposity loss … studies, including recent randomized controlled trials.

10. Reductions in body weight and percent fat mass increase the vitamin D status of obese subjects: a systematic review and metaregression analysis.

Pannu PK, Zhao Y, Soares MJ.

Nutr Res. 2016 Mar;36(3):201-13. doi: 10.1016/j.nutres.2015.11.013. Epub 2015 Nov 26. Review.

PMID: 26923506

http://sci-hub.cc/10.1016/j.nutres.2015.11.013

Reviews studies on lifestyle-induced weight loss and 25(OH)D levels in nonsupplemented cohorts.

 

Perpetuating effects of androgen deficiency on insulin-resistance.

Cameron JL, Jain R, Rais M, White AE, Beer TM, Kievit P, Winters-Stone K, Messaoudi I, Varlamov O.

Int J Obes (Lond). 2016 Aug 18. doi: 10.1038/ijo.2016.148. [Epub ahead of print]

PMID: 27534842

http://sci-hub.cc/10.1038/ijo.2016.148

… intact and orchidectomized male rhesus macaques … Western-style, high-fat/calorie-dense diet (WSD) followed by four months of caloric restriction (CR). … gained similar proportions of body fat, developed visceral and subcutaneous adipocyte hypertrophy, and became insulin resistant in response to the WSD. CR reduced body fat in both groups, but reversed insulin resistance only in intact animals. Orchidectomized animals displayed progressive sarcopenia, which persisted after the switch to CR. ... Physical activity levels showed a negative correlation with body fat and insulin sensitivity.

 

Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise.

Hord JM, Botchlett R, Lawler JM.

Exp Gerontol. 2016 Aug 14. pii: S0531-5565(16)30257-1. doi: 10.1016/j.exger.2016.08.006. [Epub ahead of print]

PMID: 27534381

http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0531556516302571

lifelong mild (8%) caloric restriction (CR) and lifelong CR+voluntary wheel running (WR) … healthy membrane environment in plantaris muscle fibers … [old] OCR and OCRWR provided significant protection

 

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

Pop LC, Sukumar D, Schneider SH, Schlussel Y, Stahl T, Gordon C, Wang X, Papathomas TV, Shapses SA.

Osteoporos Int. 2016 Aug 17. [Epub ahead of print]

PMID: 27535752

http://sci-hub.cc/doi/10.1007/s00198-016-3735-z

After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % i

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Combined effects of resistance training and calorie restriction on mitochondrial fusion and fission proteins in rat skeletal muscle.
Kitaoka Y, Nakazato K, Ogasawara R.
J Appl Physiol (1985). 2016 Aug 18:jap.00465.2016. doi: 10.1152/japplphysiol.00465.2016. [Epub ahead of print]
PMID: 27539498
[The paper is pdf=availed.]
Four weeks of resistance training (thrice/week) increased gastrocnemius muscle weight in ad libitum-fed (AL) rats by 14% [but only] in CR rats (7.4%). … CR elevated the levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein, a known master regulator of mitochondrial biogenesis. Resistance training alone also increased PGC-1α levels in skeletal muscle. … resistance training with CR elevated the levels of proteins involved in mitochondrial fusion … no effect of CR on fission [Thus] CR attenuates resistance training-induced muscle hypertrophy, but may enhance mitochondrial adaptations in skeletal muscle.

Effect of cold environment on hepatic microsomal Δ6 and Δ9 desaturase activity of male rats.
Losada AV, Peluffo RO.
Lipids. 1987 Aug;22(8):583-8. doi: 10.1007/BF02537285.
PMID: 27519851
Male rats maintained at 24 C and then shifted to 5 C for 5 days increased food intake and decreased in growth rate and food conversion. No modification was observed in Δ6 desaturase activity, while Δ9 desaturase activity decreased after this period of time. These results were confirmed by liver microsomal and mitochondrial fatty acid composition. The phospholipid composition of liver microsomes was unaltered, whereas in mitochondria, phosphatidylcholine and sphingomyelin decreased and phosphatidylethanolamine increased due to the cold environment. The influence of food intake and weight changes on fatty acid metabolism was studied using (i) rats maintained at 5 C with restricted food intake to match the food intake of those kept at 24 C with food ad libitum and (ii) rats maintained at 24 C whose food intake was also restricted so that their growth rate would be the same as that of rats maintained at 5 C with food ad libitum, respectively. These results indicate that the negative metabolic balance state of these cold conditions is not an active factor modifier of Δ6 desaturase activity, whereas it decreases Δ9 desaturase activity, reflecting the lipogenic characteristics of the latter enzyme.

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Perpetuating effects of androgen deficiency on insulin-resistance.
Cameron JL, Jain R, Rais M, White AE, Beer TM, Kievit P, Winters-Stone K, Messaoudi I, Varlamov O.
Int J Obes (Lond). 2016 Aug 18. doi: 10.1038/ijo.2016.148. [Epub ahead of print]
PMID: 27534842
http://sci-hub.cc/10.1038/ijo.2016.148
Middle-aged (11-12-yo) intact and orchidectomized male rhesus macaques were maintained for two months on a standard chow diet, and then exposed for six months to a Western-style, high-fat/calorie-dense diet (WSD) followed by four months of caloric restriction (CR). … CR reduced body fat in both groups, but reversed insulin resistance only in intact animals. Orchidectomized animals displayed progressive sarcopenia, which persisted after the switch to CR. Androgen deficiency was associated with increased levels of interleukin-6 and macrophage-derived chemokine (CCL22), both of which were elevated during CR. Physical activity levels showed a negative correlation with body fat and insulin sensitivity.

Changes in circulating vitamin D levels with loss of adipose tissue.
Gangloff A, Bergeron J, Lemieux I, Després JP.
Curr Opin Clin Nutr Metab Care. 2016 Aug 16. [Epub ahead of print]
PMID: 27537278
REVIEW … Improvements of circulating 25(OH)D levels with adiposity loss through lifestyle interventions without supplementation is being reported by a growing number of studies, including recent randomized controlled trials.
10. Reductions in body weight and percent fat mass increase the vitamin D status of obese subjects: a systematic review and metaregression analysis.
Pannu PK, Zhao Y, Soares MJ.
Nutr Res. 2016 Mar;36(3):201-13. doi: 10.1016/j.nutres.2015.11.013. Epub 2015 Nov 26. Review.
PMID: 26923506
http://sci-hub.cc/10.1016/j.nutres.2015.11.013
Reviews studies on lifestyle-induced weight loss and 25(OH)D levels in nonsupplemented cohorts.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.
Pop LC, Sukumar D, Schneider SH, Schlussel Y, Stahl T, Gordon C, Wang X, Papathomas TV, Shapses SA.
Osteoporos Int. 2016 Aug 17. [Epub ahead of print]
PMID: 27535752
http://sci-hub.cc/doi/10.1007/s00198-016-3735-z
women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05).


Combined effects of resistance training and calorie restriction on mitochondrial fusion and fission proteins in rat skeletal muscle.
Kitaoka Y, Nakazato K, Ogasawara R.
J Appl Physiol (1985). 2016 Aug 18:jap.00465.2016. doi: 10.1152/japplphysiol.00465.2016. [Epub ahead of print]
PMID: 27539498
[The paper is pdf-availed.]
Four weeks of resistance training (thrice/week) increased gastrocnemius muscle weight in ad libitum-fed (AL) rats by 14% [but only] in CR rats (7.4%). … CR elevated the levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein, a known master regulator of mitochondrial biogenesis. Resistance training alone also increased PGC-1α levels in skeletal muscle. … resistance training with CR elevated the levels of proteins involved in mitochondrial fusion … no effect of CR on fission [Thus] CR attenuates resistance training-induced muscle hypertrophy, but may enhance mitochondrial adaptations in skeletal muscle.

Calorie restriction in humans: An update.
Most J, Tosti V, Redman LM, Fontana L.
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.
PMID: 27544442
http://sci-hub.cc/10.1016/j.arr.2016.08.005
those who are self-practicing this dietary intervention allows us to speculate on longer-term effects of more severe CR in humans.
[From the full-text: Heart rate variability in the CR practitioners was comparable with published norms for healthy men and women 20 years younger (Stein et al., 2012) ... hormonal adaptations that have been reported in long-lived CR rodents, and are also implicated in the pathogenesis of several common cancers (Longo and Fontana, 2010), occurred in these individuals practicing severe CR.]

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Therapies for Prevention and Treatment of Alzheimer's Disease.

Mendiola-Precoma J, Berumen LC, Padilla K, Garcia-Alcocer G.

Biomed Res Int. 2016;2016:2589276. doi: 10.1155/2016/2589276. Epub 2016 Jul 28. Review.

PMID: 27547756

http://www.hindawi.com/journals/bmri/2016/2589276/

[it is a review including discussions on CR.]

 

[Only about 5% of the general population have fibromalgia and maybe it is only associated with gluten intolerance because of similar symptoms, but the comparison of gluten-free diets and CR diets was of interest, anyway to me it was.  The paper is pdf-availed.]

The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial.

Slim M, Calandre EP, Garcia-Leiva JM, Rico-Villademoros F, Molina-Barea R, Rodriguez-Lopez CM, Morillas-Arques P.

J Clin Gastroenterol. 2016 Aug 19. [Epub ahead of print]

PMID: 27548732

gluten-free diet (GFD) compared with a hypocaloric diet (HCD) among patients with fibromyalgia … GFD and HCD groups (-2.44±0.40 for the GFD; -2.10±0.37 for the HCD; P=0.343).

 

Complete and Voluntary Starvation of 50 days.

Elliott B, Mina M, Ferrier C.

Clin Med Insights Case Rep. 2016 Aug 11;9:67-70. doi: 10.4137/CCRep.S39776. eCollection 2016.

PMID: 27547044

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982520/

(96.8 kg; BMI, 30.2 kg m(-1)) … only tea, coffee, water, and a daily multivitamin … (final 75.4 kg; BMI, 23.5 kg m(-1)). A surprising resilience to effects of fasting on activity levels and physical function is noted. Plasma samples are suggestive of early impairment of liver function, and perturbations to cardiovascular dynamics are also noted. One month following resumption of feeding behavior, body weight was maintained (75.0 kg; BMI, 23.4 kg m(-1)).

 

[Papers’ titles inform.]

Chemotherapy: Putting tumours on a diet.

Seton-Rogers S.

Nat Rev Cancer. 2016 Aug 12. doi: 10.1038/nrc.2016.90. [Epub ahead of print] No abstract available.

PMID: 27515921

http://sci-hub.cc/10.1038/nrc.2016.90

Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity.

Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M, Morgan TE, Longo VD.

Cancer Cell. 2016 Jul 11;30(1):136-46. doi: 10.1016/j.ccell.2016.06.005.

PMID: 27411588

http://sci-hub.cc/10.1016/j.ccell.2016.06.005

Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S, Castoldi F, Jacquelot N, Yamazaki T, Senovilla L, Marino G, Aranda F, Durand S, Sica V, Chery A, Lachkar S, Sigl V, Bloy N, Buque A, Falzoni S, Ryffel B, Apetoh L, Di Virgilio F, Madeo F, Maiuri MC, Zitvogel L, Levine B, Penninger JM, Kroemer G.

Cancer Cell. 2016 Jul 11;30(1):147-60. doi: 10.1016/j.ccell.2016.05.016.

PMID: 27411589

http://sci-hub.cc/10.1016/j.ccell.2016.05.016

 

Differential Development of Inflammation and Insulin Resistance in Different Adipose Tissue Depots Along Aging in Wistar Rats: Effects of Caloric Restriction.

Sierra Rojas JX, García-San Frutos M, Horrillo D, Lauzurica N, Oliveros E, Carrascosa JM, Fernández-Agulló T, Ros M.

J Gerontol A Biol Sci Med Sci. 2016 Mar;71(3):310-22. doi: 10.1093/gerona/glv117. Epub 2015 Sep 29.

PMID: 26419977

http://sci-hub.cc/10.1093/gerona/glv117

Caloric restriction ameliorated insulin resistance and inflammation in all tissues, being more effective in subcutaneous and brown adipose tissues. These data demonstrate differential susceptibility of the different adipose depots to the development of age-associated insulin resistance and inflammation.

Edited by AlPater

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Time-restricted feeding in young men performing resistance training: A randomized controlled trial.

Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW.

Eur J Sport Sci. 2016 Aug 22:1-8. [Epub ahead of print]

PMID: 27550719

http://sci-hub.cc/10.1080/17461391.2016.1223173

time-restricted feeding (TRF) … TRF reduced energy intake by 650 kcal per day of TRF, but did not affect total body composition ... Cross-sectional area of the biceps brachii and rectus femoris increased in both groups. Effect size data indicate a gain in lean soft tissue in the group that performed RT without TRF (+2.3 kg, d = 0.25). Upper and lower body strength and lower body muscular endurance increased in both groups, but effect sizes demonstrate greater improvements in the TRF group … short-term RT in young males.

 

Differences in genome-wide gene expression response in peripheral blood mononuclear cells between young and old men upon caloric restriction.

Van Bussel IP, Jolink-Stoppelenburg A, De Groot CP, Müller MR, Afman LA.

Genes Nutr. 2016 May 6;11:13. doi: 10.1186/s12263-016-0528-0. eCollection 2016.

PMID: 27551314

Expression of 554 genes showed a different response between young and old men upon CR. … short period of CR is not effective in old men regarding immune-related pathways while it is effective in young

 

The effect of low-carbohydrates calorie-restricted diet on visceral adipose tissue and metabolic status in psoriasis patients receiving TNF-alpha inhibitors: results of an open label controlled, prospective, clinical study.

Campanati A, Molinelli E, Ganzetti G, Giuliodori K, Minetti I, Taus M, Catani M, Martina E, Conocchiari L, Offidani A.

J Dermatolog Treat. 2016 Aug 23:1-7. [Epub ahead of print]

PMID: 27552000

http://sci-hub.cc/10.1080/09546634.2016.1214666

[CR improves metabolism and psoriasis response to their treatment.]

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Differences in genome-wide gene expression response in peripheral blood mononuclear cells between young and old men upon caloric restriction.

Van Bussel IP, Jolink-Stoppelenburg A, De Groot CP, Müller MR, Afman LA.

Genes Nutr. 2016 May 6;11:13. doi: 10.1186/s12263-016-0528-0. eCollection 2016.

PMID: 27551314

https://genesandnutrition.biomedcentral.com/articles/10.1186/s12263-016-0528-0

Ten healthy young men, aged 20-28, and nine healthy old men, aged 64-85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. … peripheral blood mononuclear cells (PBMCs) … Expression of 554 genes showed a different response between young and old men upon CR. … downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old … most potential regulators were controlling the immune response.

 

[Khurram introduced the full paper and Dean criticized it in the Forum.]

Ageing: Dietary protection for genes.

Oshima J, Martin GM.

Nature. 2016 Aug 24. doi: 10.1038/nature19427. [Epub ahead of print] No abstract available.

PMID: 27556941

http://sci-hub.cc/10.1038/nature19427

Dietary restriction … reduce DNA damage and extend lifespan in mice modelling human DNA-repair disorders. ... the study should provide much-needed momentum for efforts to discover pharmacological mimetics of dietary restriction that can be used in humans. But given the enormous genetic and environmental diversity between humans, and the remarkably varied responses of different strains of mice to dietary restriction10, the responses of individuals to such drugs will probably vary greatly. Large-scale clinical trials will be required before dietary restriction can be recommended as a general treatment for protecting genes during usual ageing.

      Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.

Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH.

Nature. 2016 Aug 24. doi: 10.1038/nature19329. [Epub ahead of print]

PMID: 27556946

http://sci-hub.cc/10.1038/nature19329

Mice … lifespan to 4-6 months … dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice … retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum.

 

Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue.

Rogers NH, Landa A, Park S, Smith RG.

Aging Cell. 2012 Dec;11(6):1074-83. doi: 10.1111/acel.12010. Epub 2012 Oct 24.

PMID: 23020201

Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839316/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839316/pdf/nihms514414.pdf

subcutaneous white adipose tissue (sWAT) ... mice subjected to 40% caloric restriction for 12 months are of body weight similar to 3-month-old ad lib fed mice, but display sWAT resembling that of age-matched ad lib fed mice (devoid of brown adipose-like morphology).

 

Fasting and Caloric Restriction in Cancer Prevention and Treatment.

Brandhorst S, Longo VD.

Recent Results Cancer Res. 2016;207:241-66. doi: 10.1007/978-3-319-42118-6_12.

PMID: 27557543

http://sci-hub.cc/10.1007/978-3-319-42118-6_12

calorie restriction (CR) or fasting demonstrate a wide range of beneficial effects able to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories

 

Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation.

Kim CH, Lee EK, Choi YJ, An HJ, Chung HO, Park DE, Ghim BC, Yu BP, Bhak J, Chung HY.

Aging Cell. 2016 Aug 25. doi: 10.1111/acel.12513. [Epub ahead of print]

PMID: 27561685

http://onlinelibrary.wiley.com/doi/10.1111/acel.12513/full

kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats … hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. … may be important to CR's health- and life-prolonging effects.

 

Non-coding RNA molecules connect calorie restriction and lifespan.

Abraham KJ, Ostrowski LA, Mekhail K.

J Mol Biol. 2016 Aug 22. pii: S0022-2836(16)30334-5. doi: 10.1016/j.jmb.2016.08.020. [Epub ahead of print] Review.

PMID: 27561708

http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0022283616303345

non-coding RNA molecules act as mediators and targets of lifespan-extending calorie restriction. We also highlight how these RNA molecules connect calorie restriction to its effects on genome stability, cell metabolism, programmed cell death, senescence, cancer, and neurodegeneration.

Edited by AlPater

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Brain regions involved in ingestive behavior and related psychological constructs in people undergoing calorie restriction.
Kahathuduwa CN, Boyd LA, Davis T, O'Boyle M, Binks M.
Appetite. 2016 Aug 23. pii: S0195-6663(16)30429-9. doi: 10.1016/j.appet.2016.08.112. [Epub ahead of print] Review.
PMID: 27565377
http://www.sciencedirect.com/science/article/pii/S0195666316304299
http://ac.els-cdn.com/S0195666316304299/1-s2.0-S0195666316304299-main.pdf?_tid=fc329424-6d6d-11e6-8846-00000aab0f6b&acdnat=1472423163_3f962a65dd845a7b33884c6da6bb6344
[The paper seems to draw distinctions between short-term fasting, extended CR, and restrained eating regarding their effects on our psyche, which may vary with our weight/body fatness, with much of the emphasis on brain regions affected and how these brain regions relate to our psyche.]

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Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling.

Fabbiano S, Suárez-Zamorano N, Rigo D, Veyrat-Durebex C, Stevanovic Dokic A, Colin DJ, Trajkovski M.

Cell Metab. 2016 Aug 24. pii: S1550-4131(16)30374-6. doi: 10.1016/j.cmet.2016.07.023. [Epub ahead of print]

PMID: 27568549

http://sci-hub.cc/10.1016/j.cmet.2016.07.023

[in https://www.crsociety.org/index.php?app=core&module=search&do=search&fromMainBar=1 Dean has a thorough discussion of the paper leaving little to be said.]

 

Cutting back on the essentials; can manipulating intake of specific amino acids modulate health and lifespan?

Brown-Borg HM, Buffenstein R.

Ageing Res Rev. 2016 Aug 25. pii: S1568-1637(16)30204-5. doi: 10.1016/j.arr.2016.08.007. [Epub ahead of print] Review.

PMID: 27570078

http://sci-hub.cc/10.1016/j.arr.2016.08.007

[it is a 44 paper review and quite thorough.  New to me, was naked mole-rats have a third the serum methionine levels of wild type mice and Ames dwarf mice have greatly increased methionine flux.]

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A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity.

Catenacci VA, Pan Z, Ostendorf D, Brannon S, Gozansky WS, Mattson MP, Martin B, MacLean PS, Melanson EL, Troy Donahoo W.

Obesity (Silver Spring). 2016 Sep;24(9):1874-83. doi: 10.1002/oby.21581.

PMID: 27569118

http://onlinelibrary.wiley.com/doi/10.1002/oby.21581/full

http://onlinelibrary.wiley.com/doi/10.1002/oby.21581/epdf

alternate-day fasting (ADF) … sensitivity index (Si) … moderate daily caloric restriction (CR … CR (-400 kcal/day … At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit; however, there were no significant between-group differences in change in weight (mean ± SE; ADF -8.2 ± 0.9 kg, CR -7.1 ± 1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow-up, there were no significant differences in weight regain; however, changes from baseline in % fat mass and lean mass were more favorable in ADF.

 

[Dean Comment: The somewhat ambiguous statement "ADF achieved a 376 kcal/day greater energy deficit..." is exactly as it sounds - a 376 kcal/day greater deficit than the moderate daily CR subjects. Subjects were provided with food during the 8-week study, and instructed to report any extra food they ate. It seems quite possible the ADF folks may have underreported the extra food they ate. Otherwise, an 376 kcal/day extra deficit for 8-weeks (21,000 fewer kcal over the study period) would seem like it should have resulted in more than the extra 2-lbs of weight loss observed in the ADF folks.]

 

Serotonin signaling mediates protein valuation and aging.

Ro J, Pak G, Malec PA, Lyu Y, Allison DB, Kennedy RT, Pletcher SD.

Elife. 2016 Aug 23;5. pii: e16843. doi: 10.7554/eLife.16843.

PMID: 27572262

https://publishing-cdn.elifesciences.org/16843/elife-16843-v1.pdf

perceived value of dietary protein is a critical determinant of its effect on lifespan … independent of food consumption… dietary restriction

 

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA-DNA hybrids.

Abraham KJ, Chan JN, Salvi JS, Ho B, Hall A, Vidya E, Guo R, Killackey SA, Liu N, Lee JE, Brown GW, Mekhail K.

Nucleic Acids Res. 2016 Aug 29. pii: gkw752. [Epub ahead of print]

PMID: 27574117

http://nar.oxfordjournals.org/content/early/2016/08/29/nar.gkw752.full

http://nar.oxfordjournals.org/content/early/2016/08/29/nar.gkw752.full.pdf+html

[Maybe magnesium has a special role inCR?]

Mg2+, acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA-DNA hybrids, or R-loops. … we identify Mg2+ as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes.

Edited by Dean Pomerleau
Added comment regarding PMID 27569118

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Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo.
Jeon H, Kim JH, Lee E, Jang YJ, Son JE, Kwon JY, Lim TG, Kim S, Park JH, Kim JE, Lee KW.
Oncotarget. 2016 Aug 25. doi: 10.18632/oncotarget.11615. [Epub ahead of print]
PMID: 27579534
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=11615&path%5B%5D=36780

[The below paper is pdf-availed.]
Effects of Weight Loss on Lean Mass, Strength, Bone, and Aerobic Capacity.
Weiss EP, Jordan RC, Frese EM, Albert SG, Villareal DT.
Med Sci Sports Exerc. 2016 Aug 30. [Epub ahead of print]
PMID: 27580151
Overweight, sedentary women and men (n=52, 45-65y) were randomized to 6-8% weight loss by using calorie restriction (CR), endurance exercise (EX), or both (CREX). The CR and CREX groups underwent counseling to reduce energy intake by 20% and 10%, respectively. The EX and CREX groups exercised 7.4±0.5 and 4.4±0.5 hr/wk, respectively. … Weight loss was ~7% in all groups. Decreases in whole body (~2%, p=0.003) and lower extremity (~4%, p<0.0001) lean mass occurred in the CR group (both p<0.05). Despite similar weight loss, these reductions were attenuated in the CREX group (~1%, p=0.44 and ~2%, p=0.05, respectively) and absent in the EX group. Absolute aerobic capacity decreased ~6% in the CR group (p=0.04), was unchanged in the CREX group (p=0.28) and increased ~15% in the EX group (p<0.0001). No changes in muscle strength or bone

[The title is different in the pdf copy.  The hypocaloric diet had not a lot of effect.]
Poly is more effective than monounsaturated fat for dietary management in the metabolic syndrome: The muffin study.
Miller M, Sorkin JD, Mastella L, Sutherland A, Rhyne J, Donnelly P, Simpson K, Goldberg AP.
J Clin Lipidol. 2016 Jul-Aug;10(4):996-1003. doi: 10.1016/j.jacl.2016.04.011. Epub 2016 May 6.
PMID: 27578132
http://sci-hub.cc/10.1016/j.jacl.2016.04.011
hypocaloric MUFA or PUFA-enriched diet after weight stabilization on an AHA step I diet. Participants consumed 3 MUFA-enriched or PUFA-enriched muffins daily with additional supplementation as required to ensure 25%-50% increases in dietary fat intake from these sources at the expense of SFA and the opposing unsaturated fat. … weight loss (MUFA: -2.3 ± 1 kg, P = .06; PUFA: -4.6 ± 2 kg; P = .002), but PUFA was also associated with reductions in triglycerides (TG) (-30 ± 18 mg/dL, P = .02), systolic blood pressure (BP) (-7 ± 3 mm Hg, P = .01), diastolic BP (DBP) (-4 ± 2 mm Hg, P = .01) and improved flow mediated dilation (FMD) (7.1% ± 1.8% vs 13.6% ± 2%, absolute increase; P = .0001). When compared to MUFA treatment, PUFA intervention was associated with reduced TG (P = .04) and DBP (P = .07) as well as increased FMD (P = .04) … 25% (4 of 16) assigned to PUFA and 13% (3 of 23) to MUFA converted to non-MetS status.

[The second below paper is discussed in https://www.crsociety.org/topic/11488-cold-exposure-other-mild-stressors-for-increased-health-longevity/page-23?do=findComment&comment=18422by Dean.]
Metabolism: Diet restriction makes fat brown.
[No authors listed]
Nature. 2016 Aug 31;537(7618):10. doi: 10.1038/537010b. No abstract available.
PMID: 27582190
http://sci-hub.cc/10.1038/537010b
Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling.
Fabbiano S, Suárez-Zamorano N, Rigo D, Veyrat-Durebex C, Stevanovic Dokic A, Colin DJ, Trajkovski M.
Cell Metab. 2016 Aug 24. pii: S1550-4131(16)30374-6. doi: 10.1016/j.cmet.2016.07.023. [Epub ahead of print]
PMID: 27568549
http://sci-hub.cc/10.1016/j.cmet.2016.07.023

Long-Term Effects of a Randomised Controlled Trial Comparing High Protein or High Carbohydrate Weight Loss Diets on Testosterone, SHBG, Erectile and Urinary Function in Overweight and Obese Men.
Moran LJ, Brinkworth GD, Martin S, Wycherley TP, Stuckey B, Lutze J, Clifton PM, Wittert GA, Noakes M.
PLoS One. 2016 Sep 1;11(9):e0161297. doi: 10.1371/journal.pone.0161297. eCollection 2016.
PMID: 27584019
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161297
Total testosterone, sex hormone binding globulin and free testosterone increased (P<0.001) and the total IIEF increased (P = 0.017) with no differences between diets (P≥0.244). Increases in testosterone (P = 0.037) and sex hormone binding globulin (P<0.001) and improvements in the total IIEF (P = 0.041) occurred from weeks 0-12 with a further increase in testosterone from week 12-52 (P = 0.002). Increases in free testosterone occurred from week 12-52 (p = 0.002). The IIEF erectile functon domain, lower urinary tract symptoms and sexual desire did not change in either group (P≥0.126).

[see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466591/figure/fig3/also.]
Macronutrient Intake-Associated FGF21 Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial.
Heianza Y, Ma W, Huang T, Wang T, Zheng Y, Smith SR, Bray GA, Sacks FM, Qi L.
Diabetes Care. 2016 Aug 31. pii: dc161111. [Epub ahead of print]
PMID: 27581055
http://sci-hub.cc/10.2337/dc16-1111
significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake-decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.

Is human white adipose tissue bright during exercise?
Bülow J.
Am J Clin Nutr. 2016 Aug 17. pii: ajcn141481. [Epub ahead of print] No abstract available.
PMID: 27534635 http://sci-hub.cc/10.3945/ajcn.116.141481
==============================
Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss.
Nakhuda A, Josse AR, Gburcik V, Crossland H, Raymond F, Metairon S, Good L, Atherton PJ, Phillips SM, Timmons JA.
Am J Clin Nutr. 2016 Aug 3. pii: ajcn132563. [Epub ahead of print]
PMID: 27488235
Free Article http://ajcn.nutrition.org/content/104/3/557.abstract
We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction-mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a more-brown adipocyte phenotype.

Weight management and exercise: any advantage?
Bray GA.
Am J Clin Nutr. 2016 Aug 17. pii: ajcn141499. [Epub ahead of print] No abstract available.
PMID: 27534641
http://sci-hub.cc/10.3945/ajcn.116.141499
======================================
Effects of matched weight loss from calorie restriction, exercise, or both on cardiovascular disease risk factors: a randomized intervention trial.
Weiss EP, Albert SG, Reeds DN, Kress KS, McDaniel JL, Klein S, Villareal DT.
Am J Clin Nutr. 2016 Jul 27. pii: ajcn131391. [Epub ahead of print]
PMID: 27465384
http://sci-hub.cc/10.3945/ajcn.116.131391
[Weight loss via CR, exercise or together improves cardiovascular risk factors comparably for the same weight loss.]

Distinct lipid profiles predict improved glycemic control in obese, nondiabetic patients after a low-caloric diet intervention: the Diet, Obesity and Genes randomized trial.
Valsesia A, Saris WH, Astrup A, Hager J, Masoodi M.
Am J Clin Nutr. 2016 Aug 10. pii: ajcn137646. [Epub ahead of print]
PMID: 27510538
Free Article
http://ajcn.nutrition.org/content/104/3/566.long
http://ajcn.nutrition.org/content/104/3/566.full.pdf+html
[The title conveys the message of the paper for me.]

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[Well, it has been discussed by Michael and others that branched chain amino acid restriction is a parallel to or involved in CR effects.  I could not find the full-text to the first below paper.]

Is Leucine Restriction/Deprivation an Inducer of Adipose Browning? A Response to Jens Lund.

Duan Y, Li F, Yin Y.

Trends Pharmacol Sci. 2016 Aug 29. pii: S0165-6147(16)30093-1. doi: 10.1016/j.tips.2016.07.004. [Epub ahead of print] No abstract available.

PMID: 27587223

Keywords: adipose browning, leucine, obesity.

Adult humans do not possess active brown adipose tissue (BAT). If certain white depots could develop brownish characteristics, it could help to reduce the adverse effects of white adipose tissue (WAT) and to improve metabolic health [1]. WAT is principally devoid of uncoupling protein 1 (UCP-1) at thermoneutrality, whereas BAT demonstrates small but significant UCP-1 gene expression at thermoneutrality. The molecular signature that identifies brown and brownlike adipocytes is UCP-1. Pragmatically, browning is defined as any significantly increased UCP-1 expression at the mRNA level occurring in what are normally regarded as WAT depots [2].

Leucine and Adipose Browning: Some Burning Issues

In a recent letter [3] in response to our article on leucine and adipose browning [4], Jens Lund suggests that leucine restriction/deprivation is a potential inducer of adipose browning. This idea is inconsistent with our argument that dietary leucine supplementation may be a promising candidate for the browning of WAT, which may play a role in the prevention and management of obesity and its associated metabolic disorders (reviewed in [4]). Evidence to support the idea of Jens Lund mainly comes from two research groups. One research group investigated the effects of leucine on energy balance by providing a leucine-deficient diet to mice [5]. This research group found that mice on a leucine-deficient diet increased the mRNA and protein expression of UCP-1 in BAT and WAT 5 and 6. The other research group reported that dietary leucine restriction by 85% for 11 weeks increased the mRNA and protein levels of UCP-1 in BAT and WAT, accompanied by an elevation of energy expenditure and attenuation of body weight gain and adiposity [7]. Given the available evidence, it seems fair to suggest the ‘browning’ potential of leucine restriction/deprivation. However, we have noted that mice in those studies were placed on a normal diet rather than on a high-fat diet. The statements ‘leucine restriction/deprivation is a potential inducer of adipose browning’ may be under the condition of a normal diet. It is worth reconsidering whether those studies can support such statements in the context of a dietary pattern that includes high fat consumption.

Indeed, emerging evidence has supported our idea, that is, in the context of a dietary pattern that includes high fat consumption, leucine supplementation contributes to the browning of WAT. For example, in the study of Binder et al. [8], the effect of leucine supplementation on expression of browning markers in a high-fat diet-fed C57BL/6J mice was investigated. There was a trend toward increased UCP-1 mRNA expression in BAT of mice after leucine treatment, although the difference was not statistically significant. Unfortunately, UCP-1 mRNA expression was not measured in WAT. These interesting results prompted the same group to carry out another research. In this research [9], diet-induced obese mice were fed a normocaloric diet to induce weight loss while receiving the leucine in drinking water (1.5% w/v) for 21 weeks. UCP-1 mRNA expression was evaluated in WAT. The results showed that in previously obese animals, leucine supplementation significantly increased mRNA expression levels of UCP-1 (almost fourfold) in the WAT. Notably, the statistically significant increase in UCP-1 mRNA expression in WAT was consistent with an increase in markers of mitochondrial function [cytochrome c oxidase subunit II (Cox-III), Cox-IV, and UCP-3] [9]. Additionally, this study and other researchers found that UCP-1 mRNA expression in BAT also tended to increase, although the difference was not statistically significant [10]. These results suggest a sign of browning in WAT and an increase in oxidative metabolism in adipose tissue. Moreover, these molecular effects may be associated with an increase in resting energy expenditure via upregulation of UCP-1. UCP-1 is specifically expressed in the inner membrane of mitochondria from brown adipocytes to generate heat by uncoupling oxidative phosphorylation [11]. Upregulation of UCP-1 expression increases thermogenesis and energy expenditure, thus conferring protection from obesity [12]. Based on the aforementioned findings, we think that leucine supplementation holds the potential to promote WAT browning in obesity, and it is very likely primarily the UCP-1 in brown adipocytes that is quantitatively responsible for the metabolic effects.

In summary, we welcome the perspective of Jens Lund [3] in highlighting the data on leucine restriction/deprivation, which are certain to shed new light on avenues of research in human health. However, we think that whether leucine supplementation or leucine restriction/deprivation holds the browning potential depends on the body condition. In particular, in the context of obesity or the development of obesity, leucine supplementation may be a browning agent. Otherwise, leucine restriction/deprivation may be a browning agent. Further studies should investigate the effect of leucine supplementation on adipocyte differentiation and/or transdifferentiation in vitro and determine its ability to eventually favor changes in white adipocyte phenotype.

    3. Important Nuances on Leucine and Adipose Browning.

Lund J.

Trends Pharmacol Sci. 2016 Sep;37(9):730-1. doi: 10.1016/j.tips.2016.06.005. Epub 2016 Jun 25. No abstract available.

PMID: 27352989

http://sci-hub.cc/10.1016/j.tips.2016.06.005

"from a human perspective leucine supplementation makes most sense, since a leucine-deprived diet is ultimately deadly and because leucine restriction is practically challenging and associated with a risk of malnutrition."

    4. Leucine in Obesity: Therapeutic Prospects.

Yao K, Duan Y, Li F, Tan B, Hou Y, Wu G, Yin Y.

Trends Pharmacol Sci. 2016 Aug;37(8):714-27. doi: 10.1016/j.tips.2016.05.004. Epub 2016 May 30. Review.

PMID: 27256112

http://sci-hub.cc/10.1016/j.tips.2016.05.004

[There is a short section called “Browning of WAT” that discusses how changing white to brown adipose tissue might help prevent or treat excess body weight.]

 

Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan.

Gillespie ZE, Pickering J, Eskiw CH.

Front Genet. 2016 Aug 18;7:142. doi: 10.3389/fgene.2016.00142. eCollection 2016. Review.

PMID: 27588026

http://www.tandfonline.com.secure.sci-hub.cc/doi/full/10.1080/15384101.2016.1224797

[Just a review of existing science on the subject, it seems.]

Edited by AlPater

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[it has seemingly been fairly quite in the CR papers publications recently, but the below paper's full-text had quite a large number of findings of my interest.]

Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.
Banks WA, Abrass CK, Hansen KM.
J Gerontol A Biol Sci Med Sci. 2016 Jan;71(1):21-9. doi: 10.1093/gerona/glu100. Epub 2014 Aug 15.
PMID: 25128822
http://sci-hub.cc/10.1093/gerona/glu100
we used a nested design of aged, calorically restricted, and refed rats ... our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue

Edited by AlPater

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Effects of self-reported calorie restriction on correlations between SIRT1 polymorphisms and body mass index and long-term weight change.

Higashibata T, Wakai K, Naito M, Morita E, Hishida A, Hamajima N, Hara M, Suzuki S, Hosono S, Takashima N, Ohnaka K, Takada A, Mikami H, Watanabe Y, Uemura H, Kubo M, Tanaka H.

Gene. 2016 Aug 31. pii: S0378-1119(16)30697-7. doi: 10.1016/j.gene.2016.08.051. [Epub ahead of print]

PMID: 27591970

http://sci-hub.cc/10.1016/j.gene.2016.08.051

No significant correlations between SIRT1 polymorphisms and BMI or long-term weight change were found in either the CR or the active groups. In the no-CR group, women with the rs1467568 G allele had a higher BMI than women without (p=0.02). Moreover, women with the rs7895833 A or rs1467568 G allele gained more weight from the age of 20years than women without these alleles (p=0.03 for rs7895833 and p=0.003 for rs1467568). In addition, the odds ratios (95% confidence intervals) of these alleles for overweight (BMI >27.5kg/m2) were significantly high in the no-CR women group (1.78 (1.06-2.99) for rs7895833 and 1.88 (1.13-3.15) for rs1467568) but not in the CR group. The results of this study suggest that CR might override the genetic contributions of the SIRT1 rs7895833 A and rs1467568 G alleles to BMI and long-term weight change.

KEYWORDS: Cross-sectional

 

[The below paper is pdf-availed and the differences in liver mitochondrial dysfuntions were large, depending on whether CR increased, did not change or decreased the lifespan of the strain of mice.]

Disentangling the effect of dietary restriction on mitochondrial function using recombinant inbred mice.

Mulvey L, Sands WA, Salin K, Carr AE, Selman C.

Mol Cell Endocrinol. 2016 Sep 2. pii: S0303-7207(16)30357-4. doi: 10.1016/j.mce.2016.09.001. [Epub ahead of print]

PMID: 27597651

strain-specific variation in lifespan under 40% DR. Strains TejJ89 (lifespan increased under DR), TejJ48 (lifespan unaffected by DR) and TejJ114 (lifespan decreased under DR) were studied following 10 months of 40% DR (13 months of age). … tissue-specific differences in the mitochondrial response in ILSXISS mice to DR

 

[The below paper is pdf-availed.]

DNP, mitochondrial uncoupling, and neuroprotection: A Little Dab'll Do Ya.

Geisler JG, Marosi K, Halpern J, Mattson MP.

Alzheimers Dement. 2016 Sep 3. pii: S1552-5260(16)32854-0. doi: 10.1016/j.jalz.2016.08.001. [Epub ahead of print]

PMID: 27599210

http://www.ncbi.nlm.nih.gov/pubmed/?term=27599210

Repurposing of DNP and the development of novel uncoupling agents with hormetic mechanisms of action provide opportunities for new breakthrough therapeutic interventions in a range of acute and chronic insidious neurodegenerative/neuromuscular conditions, all paradoxically at body weight-preserving doses.

Acknowledgment

This work was supported by the Intramural Research Program of the National Institute on Aging and by Mitochon Pharmaceuticals.

"Caloric restriction and fasting also stimulate the expression of UCPs. For example, caloric restriction increased the expression of UCP4 in the cerebral cortex of adult rats [35]. Consistent with the general notion that UCP expression is increased in response to physiological metabolic challenges such as exercise and dietary energy restriction, exposure of animals to mild hypoxia increases the expression of UCP2 in the cerebral cortex and hippocampus [75]. A ketogenic diet has also been reported to increase UCP2 expression in the brain [76]. Interestingly, as is the case with UCP1 in brown fat cells, cold temperatures induce the expression of UCP4 in neurons [35]."

35. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.

Liu D, Chan SL, de Souza-Pinto NC, Slevin JR, Wersto RP, Zhan M, Mustafa K, de Cabo R, Mattson MP.

Neuromolecular Med. 2006;8(3):389-414.

PMID: 16775390

http://www.ncbi.nlm.nih.gov/pubmed/16775390

http://sci-hub.cc/10.1385/nmm:8:3:389

"During the 80 years after the initial use of DNP in humans at very high doses for inducing weight loss in obese subjects, the knowledge base of mitochondrial bioenergetics and chemical uncoupling has expanded greatly. It was not known until recently, however, that very low doses of uncoupling agents such as DNP are effective in ameliorating disease processes and improving functional outcome in preclinical models of a range of neurological disorders that involve metabolic and oxidative stress including AD, PD, epilepsy, and ischemic stroke [61], [65] and [98] (Fig. 4). The emerging findings described in this article suggest that, similar to the broadly beneficial effects of caloric restriction, even very low levels of mitochondrial uncoupling can protect multiple organ systems against dysfunction and degeneration in preclinical models of a wide range of disorders that involve dysregulation of energy metabolism metabolic and oxidative stress. Translation to humans is the next critical step."

 

https://en.wikipedia.org/wiki/Neuropeptide_Y

Polymorphism of neuropeptide Y gene rs16147 modifies the response to a hypocaloric diet on cardiovascular risk biomarkers and adipokines.

de Luis DA, Izaola O, de la Fuente B, Primo D, Aller R.

J Hum Nutr Diet. 2016 Sep 7. doi: 10.1111/jhn.12406. [Epub ahead of print]

PMID: 27599771

http://sci-hub.cc/10.1111/jhn.12406

The main genetic variant described in NPY gene is rs16147 (G-399A) and it is located within the promoter region upstream of the gene for neropeptide Y (NPY).

We found that the rs164147 genotype affected the reduction of waist circumference, HOMA-IR, insulin, CRP and IL-6 levels in response to weight loss diet in obese subjects.

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The unexpected role of mTORC1 in intestinal stem cells during calorie restriction.

Igarashi M, Guarente L.

Cell Cycle. 2016 Aug 11:1-2. [Epub ahead of print] No abstract available.

PMID: 27592731

http://www.tandfonline.com.secure.sci-hub.cc/doi/full/10.1080/15384101.2016.1221210

[4] mTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction.

Igarashi M, Guarente L.

Cell. 2016 Jul 14;166(2):436-50. doi: 10.1016/j.cell.2016.05.044. Epub 2016 Jun 23.

PMID: 27345368

http://sci-hub.cc/10.1016/j.cell.2016.05.044

intestinal stem cells (ISCs) is instead upregulated during calorie restriction (CR). SIRT1 deacetylates S6K1, thereby enhancing its phosphorylation by mTORC1, which leads to an increase in protein synthesis and an increase in ISC number. Paneth cells in the ISC niche secrete cyclic ADP ribose that triggers SIRT1 activity and mTORC1 signaling in neighboring ISCs. Notably, the mTOR inhibitor rapamycin, previously reported to mimic effects of CR, abolishes this expansion of ISCs. … drugs that modulate pathways important in CR may exert opposing effects on different cell types.

 

L.G. is a founder of Elysium Health and consults for GSK, Sibelius, and Segterra.

 

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Microglia Priming with Aging and Stress.

Niraula A, Sheridan JF, Godbout JP.

Neuropsychopharmacology. 2016 Sep 8. doi: 10.1038/npp.2016.185. [Epub ahead of print]

PMID: 27604565

http://sci-hub.cc/10.1038/npp.2016.185

... According to a recent study on post-menopausal

obese females, a low-calorie diet for 12 weeks led to significant weight reduction which

corresponded with improved memory, enhanced grey matter volume and functional connectivity

in the hippocampus and inferior frontal gyrus (Prehn et al., 2016). Interestingly, these cognitive

changes were no longer present over a prolonged period of time, despite maintenance of reduced

weight (Prehn et al., 2016). ...

>>>>>>>>>>>>>>>>>>> 

Caloric Restriction in Older Adults-Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function.

Prehn K, Jumpertz von Schwartzenberg R, Mai K, Zeitz U, Witte AV, Hampel D, Szela AM, Fabian S, Grittner U, Spranger J, Flöel A.

Cereb Cortex. 2016 Feb 1. pii: bhw008. [Epub ahead of print]

PMID: 26838769

http://www.ncbi.nlm.nih.gov/pubmed/26838769

http://sci-hub.cc/10.1093/cercor/bhw008

 

Circulating cytokines as determinants of weight loss-induced improvements in insulin sensitivity.

Weiss EP, Reeds DN, Ezekiel UR, Albert SG, Villareal DT.

Endocrine. 2016 Sep 7. [Epub ahead of print]

PMID: 27605038

http://sci-hub.cc/10.1007/s12020-016-1093-4

[The paper states that CR and exercise may be additive in benefits, and total weight loss via their combined effects are recommended.]

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Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.

Briski KP, Alenazi FS, Shakya M, Sylvester PW.

J Neurosci Res. 2016 Sep 12. doi: 10.1002/jnr.23892. [Epub ahead of print]

PMID: 27618227

http://www.ncbi.nlm.nih.gov/pubmed/?term=27618227

http://sci-hub.cc/doi/10.1002/jnr.23892

Estradiol (E) … 12 hr-food deprivation (FD) … E- vs. oil (O)-implanted ovariectomized female rats, … free fatty acids [FFA]) ... FD decreased blood glucose in oil (O)- but not E-implanted ovariectomized female rats and elevated and reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. … sensor activity was refractory to glucose decrements in FD/O but augmented in FD/E despite stabilized glucose and elevated FFA levels. …

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Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity.

Amigo I, Menezes-Filho SL, Luévano-Martínez LA, Chausse B, Kowaltowski AJ.

Aging Cell. 2016 Sep 13. doi: 10.1111/acel.12527. [Epub ahead of print]

PMID: 27619151

http://onlinelibrary.wiley.com/doi/10.1111/acel.12527/full

Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic [Wiki says: Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters] insults … our results indicate that enhanced mitochondrial calcium retention capacity underlies the beneficial effects of CR against excitotoxic conditions. This protection may explain the many beneficial effects of CR in the aging brain.

 

Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila.

Wood JG, Jones BC, Jiang N, Chang C, Hosier S, Wickremesinghe P, Garcia M, Hartnett DA, Burhenn L, Neretti N, Helfand SL.

Proc Natl Acad Sci U S A. 2016 Sep 12. pii: 201604621. [Epub ahead of print]

PMID: 27621458

http://sci-hub.cc/10.1073/pnas.1604621113

Transposable elements (TEs) are mobile genetic elements, highly enriched in heterochromatin, that constitute a large percentage of the DNA content of eukaryotic genomes. Aging in Drosophila melanogaster is characterized by loss of repressive heterochromatin structure and loss of silencing of reporter genes in constitutive heterochromatin regions. … we found that transcripts of many genes native to heterochromatic regions and TEs increased with age in fly heads and fat bodies. A dietary restriction regimen, known to extend life span, repressed the age-related increased expression of genes located in heterochromatin, as well as TEs. We also observed a corresponding age-associated increase in TE transposition in fly fat body cells that was delayed by dietary restriction. Furthermore, we found that manipulating genes known to affect heterochromatin structure, including overexpression of Sir2, Su(var)3-9, and Dicer-2, as well as decreased expression of Adar, mitigated age-related increases in expression of TEs. Increasing expression of either Su(var)3-9 or Dicer-2 also led to an increase in life span. Mutation of Dicer-2 led to an increase in DNA double-strand breaks. Treatment with the reverse transcriptase inhibitor 3TC resulted in decreased TE transposition as well as increased life span in TE-sensitized Dicer-2 mutants. …

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Ageing: Dietary protection for genes.
Oshima J, Martin GM.
Nature. 2016 Aug 24. doi: 10.1038/nature19427. [Epub ahead of print] No abstract available.
PMID: 27556941
http://sci-hub.cc/10.1038/nature19427
Dietary restriction is known to extend lifespan in many species. It has now been shown to reduce DNA damage and extend lifespan in mice modelling human DNA-repair disorders. See Letter p.427
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.
Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH.
Nature. 2016 Aug 24. doi: 10.1038/nature19329. [Epub ahead of print]
PMID: 27556946
http://sci-hub.cc/10.1038/nature19329
Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1∆/−) ... resembles the anti-ageing response induced by dietary restriction ... Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. ... dietary restriction response in Ercc1∆/− mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1∆/− mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. ... dietary restriction preserves genome function by alleviating DNA damage.

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Editor's choice

This week in other journals.

Science  16 Sep 2016:

Vol. 353, Issue 6305, pp. 1246

Regeneration of NAD keeps mouse muscles young

   Bryan L. Ray

http://science.sciencemag.org.sci-hub.cc/content/353/6305/1246.6

Evidence for a critical role of nitric acid dihydrate (NAD) metabolism in aging is accumulating. Frederick et al. studied mice with muscle-specific depletion of nicotinamide phosphoribosyltransferase (Nampt), an enzyme needed to restore concentrations of NAD in working muscle. Muscle in young animals tolerated a large reduction in the amount of NAD without obvious loss of function. However, older control animals had decreased muscle concentrations of NAD, which correlated with decreased performance, and these effects were more pronounced in animals lacking Nampt. Restoration of NAD concentrations by feeding older animals nicotinamide riboside partially restored muscle function. Accordingly, overexpression of Nampt in muscle helped prevent the age-dependent decline in muscular function. Thus, maintenance of proper NAD metabolism in muscle appears to be needed for sustained function.

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 

Cell Metab. 10.1016/j.cmet.2016.07.005 (2016).

Fueling Performance: Ketones Enter the Mix

 

Fueling Performance: Ketones Enter the Mix.

Egan B, D'Agostino DP.

Cell Metab. 2016 Sep 13;24(3):373-375. doi: 10.1016/j.cmet.2016.08.021.

PMID: 27626197

http://sci-hub.cc/10.1016/j.cmet.2016.08.021

Abstract

Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. (2016) demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.

>>>>>>>>>>>>>>>>>>>>>>>>>>> 

Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes.

Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K.

Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.

PMID: 27475046

http://sci-hub.cc/10.1016/j.cmet.2016.07.010

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.

 

Regression of Non-Alcoholic Fatty Liver by Vitamin D Supplement: A Double-Blind Randomized Controlled Clinical Trial.

Lorvand Amiri H, Agah S, Mousavi SN, Hosseini AF, Shidfar F.

Arch Iran Med. 2016 Sep;19(9):631-638.

PMID: 27631178

12 weeks of treatment with hypocaloric diet (reduction of 500 kcal per day) plus 25 µg of calcitriol supplement or a hypocaloric diet plus placebo. … no significant differences were seen between groups after intervention. Compared with the placebo, reductions in triglyceride and an increase in HDL cholesterol were seen over the 12 weeks of intervention in the calcitriol group (P = 0.002 and P = 0.004). AST level was decreased in the calcitriol group (-4.2 ± 4.3 µmol/L, P < 0.001), but increased in the placebo group (12.6 ± 6.1 µmol/L, P = 0.02) after 12 weeks. Reductions in mean difference of ALT, insulin and HOMA were significantly higher in the calcitriol than placebo group (P = 0.01, P = 0.007 and 0.01).

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Protein aggregation activates erratic stress response in dietary restricted yeast cells.
Bhadra AK, Das E, Roy I.
Sci Rep. 2016 Sep 16;6:33433. doi: 10.1038/srep33433.
PMID: 27633120
http://www.nature.com/articles/srep33433
Using a yeast model of Huntington's disease, we show that contrary to expectation, aggregation of mutant huntingtin is exacerbated and activation of the unfolded protein response pathway is dampened under dietary restriction. Global proteomic analysis shows that when exposed to a single stress, either protein aggregation or dietary restriction, the expression of foldases like peptidyl-prolyl isomerase, is strongly upregulated. However, under combinatorial stress, this lead is lost, which results in enhanced protein aggregation and reduced cell survival.

Edited by AlPater

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ANNALS EXPRESS: Effect of dietary modification by calorie-restriction on cholesterol levels in lipoprotein(a) and other lipoprotein classes.

Hirowatari Y, Manita D, Kamachi K, Tanaka A.

Ann Clin Biochem. 2016 Sep 16. pii: 0004563216672247. [Epub ahead of print]

PMID: 27638928

[The paper is not pdf-availed.]

Framingham risk score (FRS) … Body mass index (BMI), waist circumference (WC), insulin resistance, FRS, total cholesterol (TC), LDL-cholesterol, and IDL-cholesterol (IDL-C) were significantly decreased by the calorie-restriction, and the protein and cholesterol levels of Lp(a) were significantly increased. The changes of BMI and WC were significantly correlated with the changes of TC, VLDL-cholesterol and chylomicron-cholesterol (CM-C), and CM-C, respectively. The change of FRS was significantly correlated with the change of IDL-C. … but Lp(a) was increased. The changes of obesity indexes and FRS were related with those of triglyceride-rich lipoproteins, e.g., IDL, VLDL and CM.

 

Comparative Approaches to Understanding the Relation Between Aging and Physical Function.

Justice JN, Cesari M, Seals DR, Shively CA, Carter CS.

J Gerontol A Biol Sci Med Sci. 2016 Oct;71(10):1243-53. doi: 10.1093/gerona/glv035. Epub 2015 Apr 23.

PMID: 25910845

http://biomedgerontology.oxfordjournals.org/content/71/10/1243.full

http://biomedgerontology.oxfordjournals.org/content/71/10/1243.full.pdf+html

[see "restriction" searches of the full-texts.]

87. Rate of aging and dietary restriction: sensory and motor function in the Fischer 344 rat.

Campbell BA, Gaddy JR.

J Gerontol. 1987 Mar;42(2):154-9.

PMID: 3819339

http://sci-hub.cc/10.1093/geronj/42.2.154

93. Changes in behaviors of male C57BL/6J mice across adult life span and effects of dietary restriction.

Fahlström A, Zeberg H, Ulfhake B.

Age (Dordr). 2012 Dec;34(6):1435-52. doi: 10.1007/s11357-011-9320-7. Epub 2011 Oct 12.

PMID: 21989972

Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528371/

111.  A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Kastman EK, Willette AA, Coe CL, Bendlin BB, Kosmatka KJ, McLaren DG, Xu G, Canu E, Field AS, Alexander AL, Voytko ML, Beasley TM, Colman RJ, Weindruch RH, Johnson SC.

J Neurosci. 2012 Aug 22;32(34):11897-904.

PMID: 23082321

J Neurosci. 2010 Jun 9;30(23):7940-7. doi: 10.1523/JNEUROSCI.0835-10.2010. Erratum in: J Neurosci. 2012 Aug 22;32(34):11904. Corrected and republished in: J Neurosci. 2012 Aug 22;32(34):11897-904.

PMID: 20534842

Free Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898557/

112. Calorie restriction in nonhuman primates: assessing effects on brain and behavioral aging.

Ingram DK, Young J, Mattison JA.

Neuroscience. 2007 Apr 14;145(4):1359-64. Epub 2007 Jan 16. Review.

PMID: 17223278

http://sci-hub.cc/10.1016/j.neuroscience.2006.10.031

113. Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys.

Yamada Y, Colman RJ, Kemnitz JW, Baum ST, Anderson RM, Weindruch R, Schoeller DA.

Exp Gerontol. 2013 Nov;48(11):1226-35. doi: 10.1016/j.exger.2013.08.002. Epub 2013 Aug 13.

PMID: 23954367

Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882119/

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