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• Effects of dietary branched-chain amino acids on reproduction and lifespan

  Reduced feeding extends lifespan in many organisms, and the growing consensus is that dietary protein contributes most to aging. The dietary amino acids responsible for accelerating aging, and their physiological roles, are an active area of study. Most animal’s diets do not match their exact dietary needs, resulting in overconsumption of some nutrients to attain sufficient levels of other nutrients. One important study with flies has shown that diets with an amino acid composition matched to the animal’s needs increased development rate, reduced feeding, and extended lifespan. We are following up on this study using our grasshopper model, which is larger and more amenable to tracking individuals.

  We force-fed adult female grasshoppers a diet designed to match the amino acid composition of vitellogenin (the precursor to egg yolk protein). Production of this protein is a major nutrient demand. A comparison group was fed an isonitrogenous diet (i.e., they consumed the same total molar quantity of amino acids), but with a composition of amino acids that did not match vitellogenin. Grasshoppers on the vitellogenin-matched diet reproduced more eggs faster than grasshoppers on the unbalanced diet. We are now testing the blood of animals from this study for storage proteins, to test for a physiological storage that serves as a threshold for commitment to reproduction.

  Future studies in this area will include:

  • test vitellogenin-matched diets on the development of juvenile males, so determine whether the diet matches the needs of both sexes and other stages;
  • design dry, artificial diets that have a similar amino acid profile to vitellogenin;
  • identifying the age at commitment to reproduction by starting grasshoppers on the vitellogenin-balanced diet, and the abruptly switching to a low amino acid diet at various ages. 

Research Projects

• Oxidation of amino acids underlying life-extension

  In collaboration with Dr. Marshall McCue, we examine the oxidation of specific amino acids upon either dietary restriction or dietary supplementation of that amino acid. To measure organismal oxidation, a ¹³C-labeled amino acid is force-fed to a grasshopper, and then the appearance of the ¹³C is measured in the CO₂ of the breath (which indicates oxidation).

  The branched-chain amino acids (leucine, isoleucine, valine) play important roles in life-extension via dietary restriction. They are especially potent at stimulating the Target of Rapamycin pathway (TOR), which accelerates cellular growth and shortens organismal lifespan. Oxidation of isoleucine and valine are increased upon dietary restriction, and oxidation of leucine also increases in most trials. In contrast, oxidation rates of none of these amino acids increased when the diet was supplemented with branched-chain amino acids. This suggests that oxidation is increased upon energy deficit, but not upon excessive levels of the amino acid. Oxidation of branched-chain amino acids may reduce their cellular levels upon dietary restriction, in turn contributing to increased lifespan.

  John Hatle and Ryan Koch at the National WW II museum in New Orleans, visited while attending the annual meeting of the Society for Integrative and Comparative Biology.

• Activity of enzymes that produce cellular hydrogen sulfide (H2S) in insects

  The sulfur-containing amino acids (methionine and cysteine) also play important roles in longevity. They provide the sulfur needed for production of cellular H ₂ S, which turns on cell proteastasis pathways, enhancing longevity. Counterintuitively, dietary restriction of sulfur-containing amino acids actually increases the production of H ₂ S in mice. Our group is studying the production of H₂S by insect tissues, focusing on grasshopper fat body, and comparing it to mealworm homogenates. Dr. Cathy Paterson from Florida State College at Jacksonville has led this project.

Research Team

• Primary Investigator

  John Hatle

  Terry Presidential Professor of Biology
  Office: Building 59, Room 3314
  Phone: (904) 620-2778
  Lab: Building 59, Room 2110
  E-mail: jhatle@unf.edu
  B.A. (Biology) Luther College (1991)
  Ph.D. (Evolutionary Biology) University of Louisiana-Lafayette (1998)
  Post-doctoral fellowship - Illinois State University (1998-2003)
  Joined º£½ÇÉçÇøfaculty in 2003.

• Graduate Research

  Derek Tokar also spent two years in the Hatle lab as an undergraduate. He used RNAi to knock down vitellogenin, and then studied the trade-off between reproductive investment and somatic storage (Tokar et al. 2014. Integrative and Comparative Biology). His graduate project is involves using RNAi to knockdown the grasshopper Target of Rapamycin.

Relevant Publications

• Relevant Publications

  Hatle JD*, Karjasevic A, Rehfeldt E, Nagle FS, Milano LJ, Patel S, Hiatt D, McCue MD (2019) Life-extending dietary restriction, but not dietary supplementation of branched-chain amino acids, can increase organismal oxidation rates of individual branched-chain amino acids by grasshoppers. Nutrition and Healthy Aging.

  Heck MJ, Hatle JD* (2018) Interaction of neuropeptide F and diet levels effects carbonyl levels in grasshoppers. Experimental Gerontology 113:186-192.

  Hatle JD*, Awan A, Nicholas J, Koch R, Vokrri JR, McCue MD, Williams CM, Davidowitz G, Hahn DA (2017) Life-extending dietary restriction and ovariectomy each increase leucine oxidation and alter leucine allocation in grasshopper. Experiment Gerontology 96: 155-161.

  Heck MJ ¹, Pehlivanovic M¹, Purcell JU, Hahn DA, Hatle JD* (2016) Life-extending dietary restriction reduces oxidative damage of proteins in grasshoppers but does not alter allocation of ingested nitrogen to somatic tissues. J Gerontol A Biol Sci Med Sci. doi:10.1093/gerona/glw094 (¹equal contribution)

  Tetlak AG, Burnett JB, Hahn DA, Hatle JD* (2015) Vitellogenin-RNAi and ovariectomy each increase lifespan, increase protein storage, and decrease feeding, but are not additive in grasshoppers. Biogerontology. 16:761-774. DOI 10.1007/s10522-015-9599-3

  Tokar DR ¹ , Veleta KA¹, Canzano J , Hahn DA, Hatle JD* (2014) Vitellogenin RNAi halts ovarian growth and diverts reproductive proteins and lipids in young grasshoppers. Integrative and Comparative Biology 54:931-941. doi:10.1093/icb/icu068 (¹equal contribution)

  Hatle JD*, Kellenberger JW, Viray E, Smith AM, Hahn DA (2013) Life-extending ovariectomy in grasshoppers increases somatic storage, but dietary restriction with an equivalent feeding rate does not. Experimental Gerontology 48: 966-972.

  Judd ET, Wessels FJ, Drewry MD, Grove M, Wright K, Hahn DA, Hatle JD* (2011) Ovariectomy in grasshoppers increases somatic storage, but proportional allocation of ingested nutrients to somatic tissues is unchanged. Aging Cell 10:972-979.

Support

• Funding Sources

  National Institute on Aging R15 Award (i.e., AREA grant) 2010-2013.

  National Science Foundation ($35,000 supplement to Dan Hahn's award, to fund the transcriptome project) in 2013-14.

  º£½ÇÉçÇøAcademic Affairs summer research award in 2014.

  National Institute on Aging R15 Award (i.e., AREA grant). 2016-2019. Testing direct effects of reproduction on lifespan with controlled feeding in grasshoppers. $432,000.

  º£½ÇÉçÇøTerry Presidential Professorship. 2016-2019. $22,500.