Associate Professor, Biological Sciences
Animal lifespans range widely, from several days to over a century, yet the underlying reasons for these vast differences remain poorly understood. The goal of my research program is to gain a better understanding of the molecular mechanisms underlying longevity. Mitochondria, via their contribution to energy metabolism, cell death pathways, and redox regulated signal transduction pathways, are thought to be important effectors of longevity. We use a comparative approach to study these in mammalian species, including those that are exceptionally long-lived. We are also exploring the ability of small molecules including selective estrogen receptor modulators and phytoestrogens to modulate mitochondrial function and affect aging and longevity.
Mitochondrial Network Analysis (MiNA)
Mitochondria exist in a dynamic balance of fusion/fission and biogenesis/mitophagy that determine the size and morphology of the ‘mitochondrial network’. Many of the mitochondrial phenomena we investigate exert effects on these processes and thus manifest as changes in mitochondrial network morphology. These morphological changes affect cell physiology and are therefore important to measure and understand.
To facilitate this we developed the Mitochondrial Network Analysis (MiNA) toolset as a simple set of macros making use of existing ImageJ plug-ins that allows a semi-automated analysis of mitochondrial networks in cultured mammalian cells. The tool incorporates optional preprocessing steps to enhance image quality before converting the images to binary and producing a morphological skeleton for calculating several parameters that quantitatively capture the morphology of the mitochondrial network.
This link will direct you to the downloadable manual and toolset for using MiNA to study mitochondrial networks in cultured mammalian cells. https://github.com/ScienceToolkit/MiNA
The Comparative Cellular and Molecular Biology of Longevity Database
Vertebrate species maximum lifespans vary from several years to over two centuries, and this presents an opportunity to investigate the underlying biological traits that have co-evolved with longevity. We maintain a cell and tissue bank with brain, heart, liver, and kidney samples and skeletal muscle myoblasts from over 20 mammalian, avian and reptilian species. These collections provide a means to investigate the expression levels of various putative longevity traits in the context of longevity.
The Comparative Cellular and Molecular Biology of Longevity (CCMBL) database (http://genomics.brocku.ca/ccmbl/) contains the combined datasets from dozens of studies (including ours) in which cellular and molecular traits have been measured in the context of evolved species longevity. The purpose of the CCMBL database is simply to provide a convenient repository that brings together the accumulating wealth of species longevity data that is available but distributed widely in the scientific literature. We hope that this single-source collection of information will promote an integrative appreciation of the cellular and molecular biology of longevity by providing a broad comparative framework into which new data can be inserted as it becomes available.
To suggest inclusion of a dataset, or request tissue samples for new analyses, please email: firstname.lastname@example.org
Stuart, J.A. and Robb, E.L. Bioactive Polyphenols from Wine Grapes. Springer Press, New Jeresey. 2013. 77 pp.
Stuart, J.A., Editor, Mitochondrial DNA: Methods and Protocols, 2nd edition. Volume 197 In: Methods in Molecular Biology, Human Press, Totowa, New Jersey. 2009.
Bagshaw ORM, Atkinson J, Fajardo VA, Leblanc PJ, Stuart JA. Mitochondrial-targeted therapeutic approaches for manipulating cardiolipin. In: Clinical Bioenergetics, Ed. Sergej Ostojic, Elsevier Press, 2020. 15pp. In press.
Valente AJF, Fonseca J, Moradi, F, Foran G, Necakov A, Stuart JA. Measuring mitochondrial network morphology in mitochondrial disease. In Mitochondria in Health and Sickness. Ed. Urbani A, Babu M. Springer Press, 2019. 18pp.
Page, M.M. and Stuart, J.A. In vitro measurement of mitochondrial DNA base excision repair enzyme activities. In: Mitochondrial DNA: Methods and Protocols, 2nd edition. Methods in Molecular Biology Series, J.M. Walker, Human Press, Totowa, New Jersey. Published online June 2009.
Recent Journal Articles
Stuart JA, Selim S, and McGowan S, 2019. A limited metabolomics analysis validates sonication-assisted extraction of Ice Wine grape pomace polyphenols and demonstrates their seasonal variation. Journal of Food Measurement and Characterization. 1-6.
Kurgan N, Whitley KC, Maddalena LA, Moradi F, Stoikos J, Hamstra SI, Rubie E, Kumar M, Roy BD, Woodgett JR, Stuart JA, Fajardo VA (2019) A low-therapeutic dose of lithium inhibits GSK3 and enhances myoblast fusion in C2C12 cells. Cells, 8(11), 1340; https://doi.org/10.3390/cells8111340.
Fajardo VA, Watson CJF, Bott KN, Moradi F, Maddalena LA, Turner BC, Peters SJ, LeBlanc PJ, MacNeil AJ, Stuart JA, Tupling AR, 2019. Neurogranin is expressed in mammalian skeletal muscle and inhibits calcineurin signalling and myoblast fusion. Am J Physiol Cell Physiol. 317(5):C1025-C1033. doi: 10.1152/ajpcell.00345.2018.
Bagshaw ORM, De Lange M, Renda S, Valente AJF, Stuart JA, 2019. Hypoxio: a simple solution to preventing pericellular hypoxia in cell monolayers growing at physiological oxygen levels. Cytotechnology. 71(4): 873-879.
Stuart JA, Aibueku O, Bagshaw ORM, Moradi F, 2019. Hypoxia Inducible Factors as Mediators of Reactive Oxygen/Nitrogen Species Homeostasis in Physiological Normoxia. Medical Hypotheses. 129: 109249.
Fonseca J, Moradi F, Maddalena LA, Ferreira-Tollstadius B, Selim S, Stuart JA, 2019. Resveratrol integrates metabolic and growth effects in PC3 prostate cancer cells – involvement of prolyl hydroxylase and hypoxia inducible factor-1. Oncol Lett, 17(1): 697–705.
Marquardt D, Ghelfi M, Maddalena LA, Stuart JA, Atkinson J, Harroun TA, 2019. Vitamin E-inspired Multi-scale imaging agent. Bioorganic & Medicinal Chemistry Letters, 29(1):107-114. https://doi.org/10.1016/j.bmcl.2018.10.052
Fonseca J, Moradi F, Valente AJF, Stuart JA, 2018. Oxygen and glucose levels in cell culture media determine resveratrol’s effects on growth, hydrogen peroxide production, and mitochondrial dynamics. Antioxidants, 7(11): 157. doi:10.3390/antiox7110157.
Stuart JA, Fonseca J, Moradi F, Cunningham C, Seliman B, Worsfold CR, Dolan S, Abando J, Maddalena LA, 2018. How supra-physiological oxygen levels in standard cell culture affect oxygen-consuming reactions. Oxid Med Cell Longev, Article ID 8238459.
Mazinani SA, Stuart JA, Yan H, 2018. Microwave-assisted delivery of an anticancer drug to cancer cells. RSC Advances 8: 31465-31470.
Said SA, Isedowo R, Guerin C, Nar NN, Lillie L, Bukovac S, Simone JJ, Green MR, McCormick CM, Stuart JA, 2018. Effects of long-term dietary administration of estrogen receptor-beta agonist diarylpropionitrile on ovariectomized female ICR(CD-1) mice. GeroScience 40(4):393-403.
Maddalena, L.A., Selim, S.S., Fonseca, J., Messner, H., McGowan, S., Stuart, J.A., 2017. Hydrogen peroxide production is affected by oxygen levels in mammalian cell culture. Biochem Biophys Res Commun. 493:246-251.
Mazinani, S., Moradi, F., Stuart, J.A., Yan, H., 2017 Microwave irradiation of PC3 cells at constant culture temperature alters the incorporation of BODIPY into cells and reduction of MTT. Chem Biochem. 2(26):7983-7986.
Valente, A.J.F., Maddalena, L.A., Robb, E.L., Moradi, F., Stuart, J.A., 2017. A Simple ImageJ Macro Tool for Analyzing Mitochondrial Network Morphology in Mammalian Cell Culture. Acta Histochem, 119(3):315-326.
Robb, E.L., Moradi, F., Maddalena, L.A., Valente, A., Fonseca, J., Stuart, J.A., 2017 Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2. Biochem Biophys Res Commun, 485(2):249-254.
Maddalena, L.A, Ghelfi, M., Atkinson, J., Stuart, J.A., 2017. The mitochondria-targeted imidazole substituted oleic acid ‘TPP-IOA’ affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism. Biochim Biophys Acta. 1858:73-85.
Yalagala, R.S., Mazinani, S.A., Maddalena, L.A., Stuart, J.A., Yan, F., Yan, H. 2016. Microwave-assisted syntheses of BODIPY-sugar conjugates through click chemistry and conjugate assembly into liposomes. Carbohydr Res. 2016 Apr 7;424:15-20.
Stuart, J.A., Maddalena, L.A., Merilovich, M., and Robb, E.L., 2014. A Midlife Crisis for the Mitochondrial Free Radical Theory of Aging. Healthspan and Longevity. 3(1):4.
Robb, E.L, Christoff, C.A., Maddalena, L.A., and Stuart, J.A., 2014. Mitochondrial reactive oxygen species in animal cells: relevance to aging and normal physiology. Can. J. Zool. 92(7): 603-613.
Page, M.M., Sinclair, A., Robb, E.L., Stuart, J.A., Withers, D.J., Selman, C., 2014 Fibroblasts derived from long-lived insulin receptor substrate 1 null mice are not resistant to multiple forms of stress. Aging Cell 13(5), 962-964.
Robb, E.L. and Stuart, J.A., 2014. The stilbenes resveratrol, pterostilbene and piceid affect growth and stress resistance in mammalian cells via a mechanism requiring estrogen receptor beta and the induction of Mn-superoxide dismutase. Phytochemistry, 98,164-173.
Robb, E.L. and Stuart, J.A., 2014. Multiple phytoestrogens inhibit cell growth and confer cytoprotection by inducing manganese superoxide dismutase expression. Phytother. Res. 28,120-131.