The general focus and goals of the lab are to: 1) Better understand the hormonal and nutritional regulation of endogenous hydrogen sulfide (H2S) production and metabolism in various tissues and cells, 2) Elucidate the mechanisms on an organismal, tissue, cellular, and molecular level as to which H2S effects a plethora of biological pathways giving rise to both negative and positive health related endpoints, and 3) Cultivate clinically applicable interventions utilizing diet, exercise, and pharmaceuticals to harness endogenous H2S production for beneficial health outcomes such as increased stress resistance, metabolic fitness, and lifespan.
Specially, the lab looks at the transcriptional, translational and enzymatic regulation of the mammalian H2S generating enzymes cystathionine gamma lyase (CGL), cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). Perturbations of these enzymes have been linked to hypertension, neurodegenerative diseases, osteoporosis, and the inability to positively respond to dietary restriction. We study the regulation and function of these enzymes under conditions that promote extraordinary health & longevity (e.g. during dietary/sulfur amino acid restriction, decreased growth hormone signaling, and exercise) or aging-related pathologies (e.g. atherosclerotic diets, aging, inflammation, genotoxic stress). Additionally, we study the mechanistic roles H2S, or the lack of, plays in promoting or preventing a healthy state. The work done in the lab addresses a significant gap in our understanding between health, aging and endogenous H2S metabolism with implications for clinical applications and interventions.
In other words ...
Aging is a major driving force behind disability, metabolic decline, and death. What exactly are the causes of aging and how to stop it have been questions posed by humans for most of history. From single celled model organisms to humans, dietary restriction has proven to be a potent, simple, and cost effective intervention to delay or dampen the onset of aging related pathologies. Dietary restriction offers significant endocrine, metabolic, stress resistance, and longevity benefits. Elusive are the mechanisms, molecules, pathways and triggers that account for these benefits. The lab’s purpose is to untangle the mechanisms and interactions between aging, nutrition, metabolism and stress resistance. This will provide a better understanding of these basic biological processes and ultimately give rise to clinical applications for safely, effectively, and efficiently improving healthspan and lifespan.
Yoko Henderson PhD
Hine, C; Mitchell, JR. Endpoint or Kinetic Measurment of Hydrogen Sulfide Production Capacity in Tissue Extracts. Bio-Protocol (2017).
Hine, C; Kim, HJ; Zhu, Y; Harputlugil, E; Longchamp, A; Matos, MS; Ramadoss, P; Bauerle, K; Brace, L; Asara, JM; Ozaki, CK; Cheng, SY; Singha, S; Ahn, KH; Kimmelman, A; Fisher, FM; Pissios, P; Withers, DJ; Selman, C; Wang, R; Yen, K; Longo, VD; Cohen, P; Barke, A; Kopchick, JJ; Miller, R; Hollenberg, AN; Mitchell, JR. Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production. Cell Metabolism (2017). PMID: 28591635
Hine, C; Mitchell, J. Calorie Restriction and Methionine Restriction in Control of Endogenous Hydrogen Sulfide Production by the Transsulfuration Pathway. Experimental Gerontology (2015). PMID: 25523462
Hine, C; Harputlugil, E; Zhang, Y; Ruckenstuhl, C; Lee, BC; Brace, L; Longchamp, A; Trevino-Villarreal, J; Mejia, P; Ozaki, CK; Wang, R; Gladyshev, V; Madeo, F; Mair, W; Mitchell, J. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell (2015). PMID: 2554231
For a complete list of publications, please see PubMed link: