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Found 2 results

  1. Dean Pomerleau

    New Insights into Muscle Loss

    [Note: This is another post that would fit best on a "Non-CR health science" forum. I'm posting it here on "CR Practice" because it has to do with a concern of people practicing CR.] Excessive muscle loss and wasting (sarcopenia) is a concern as people age, and since CRers weigh less, they also (generally) have less muscle mass to lose as they age, so it is a potential issue for us too. This new study [1], described in this popular press article, provides new understanding of this problem. It describes research identifying a protein (ATF4) that appears to be causally related to muscle wasting. Here is the main points of the research, summarized in the article: The protein, ATF4, is a transcription factor that alters gene expression in skeletal muscle, causing reduction of muscle protein synthesis, strength, and mass. The UI study also identifies two natural compounds, one found in apples and one found in green tomatoes, which reduce ATF4 activity in aged skeletal muscle. The findings, which were published online Sept. 3 in the Journal of Biological Chemistry, could lead to new therapies for age-related muscle weakness and atrophy. Previously, Adams and his team had identified ursolic acid, which is found in apple peel, and tomatidine, which comes from green tomatoes, as small molecules that can prevent acute muscle wasting caused by starvation and inactivity. An example of the previous work by these authors that identified ursolic acid and tomatidine as protective against muscle wasting is this publication [2]. The possible downside of these compounds is that they appear to have their effect by "enhancing skeletal muscle insulin/IGF-I signaling", which CR is known to downregulate, an effect which may very well be important for CR's health/longevity benefits. In the meantime, I'm going to continue exercising, eating apple peels and tomatoes (although usually red rather than green), to hopefully maintain skeletal muscle mass and health. --Dean ------------ [1] J Biol Chem. 2015 Sep 3. pii: jbc.M115.681445. [Epub ahead of print] Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. Ebert SM(1), Dyle MC(1), Bullard SA(1), Dierdorff JM(1), Murry DJ(1), Fox DK(1), Bongers KS(1), Lira VA(1), Meyerholz DK(1), Talley JJ(2), Adams CM(3). Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy, as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs are repressed by ursolic acid and tomatidine in aged muscle are positively regulated by the transcription factor ATF4. Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle. Copyright © 2015, The American Society for Biochemistry and Molecular Biology. PMID: 26338703 ---------------------------- [2] Cell Metab. 2011 Jun 8;13(6):627-38. doi: 10.1016/j.cmet.2011.03.020. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Kunkel SD(1), Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM. Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases. PMCID: PMC3120768 PMID: 21641545
  2. Dean Pomerleau

    Don't Abandon Those Green Tomatoes!

    In years past, the day before a killing frost, I've always picked all the tomatoes that were fairly red, and left the rest to die on the vine, figuring unless they're pretty ripe already they aren't going to ripen enough after picking to be edible. Boy was I wrong! This year, I decided to do an experiment. Two weeks ago, before the killing frost here in Western PA, I picked all the cherry tomatoes, (orange) grape tomatoes and yellow pear tomatoes in my garden, even the extremely green ones, like the one in my hand in the photo below. The photo shows the results of two weeks of ripening in bright window in my 65degF basement. They've all been ripening nicely. By now, all the tomatoes left in the image are ones that were very green when I picked them, including all the nicely ripe red/orange/yellow ones in the containers. The small container has the one's I'm planning to eat tomorrow. At this rate I should be enjoying organic, homegrown tomatoes through Christmas. I started harvesting in early July, so that is six months of harvest and at least 100lbs of tomatoes, from a 5x10ft plot, with very little effort. Pretty amazing for this part of the country! So for all you gardeners out there, next year, don't give up on those green tomatoes when a frost hits. Bring them inside to ripen and enjoy fresh tomatoes for weeks to come! --Dean
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