John P. Aris, Ph.D.
Education and Training
Ph.D. – Stanford University, Stanford, CA. Department of Biological Sciences (1985)
B.S. – Jacksonville University, Jacksonville, FL. Chemistry and Biology. Magna cum laude (1979)
Research Associate – Laboratory of Cell Biology, Rockefeller University, NY, NY. (1988-1991)
Postdoctoral Fellow – Laboratory of Cell Biology, Rockefeller University, NY, NY. (1985-1988)
Cellular Aging Overview
Human cell types can be broadly divided into cells that continue to divide over their life span and those that do not. Tissues in the human body that undergo continuous renewal, such as epithelia, depend on cells that continue to divide (i.e., stem cells and amplifying cells). Other tissues, such as most nervous tissue, contain many cells that do not divide, but remain functional over many years or decades (e.g., motor neurons). Aging in both types of cells involves characteristic changes due to loss of function over time. Cells that do not divide undergo chronological aging, which limits how long they remain viable and functional. Cells that divide undergo replicative aging, which limits how many times they can divide. The goal of our studies is to identify and characterize processes that cause chronological and / or replicative aging of cells.
Our studies use the budding (or baker’s) yeast Saccharomyces cerevisiae as a model eukaryotic cell type. We use this yeast as an experimental system because of the ease of using various approaches in biochemistry, cell biology, genetics, and molecular biology. Studies in yeast are relevant to human cells because many of the fundamental biological mechanisms of aging are the same. Our goal is to pursue an understanding of mechanisms that regulate chronological and replicative life span in yeast cells and extend these studies to other eukaryotic cell types, such as human cells. Insights regarding aging processes in yeast should improve our understanding of general mechanisms that regulate aging in eukaryotic cells, including human cells.
Single gene mutations that affect chronological and / or replicative life span have been identified in yeast. This is a profound result because it indicates that life span is directly influenced by genes. One of these genes, SIR2, influences the life span of yeast as well as other organisms, such as worms, flies, and mammals. Furthermore, the yeast SIR2 gene is the founding member of a family of genes that are known as sirtuins, many of which have been implicated in life span. One of the goals of our research is to identify genes that influence life span. By identifying and studying such genes, we hope to learn more about the mechanisms and pathways that influence the aging process.
Cellular Aging in Yeast
Chronological aging is the process by which non-dividing cells lose viability. In yeast, chronological aging takes place during a non-dividing state known as stationary phase. Stationary phase is a “quiescent” state in which cells exhibit a specific set of phenotypic characteristics, such as a reinforced cell wall, resistance to environmental stress, and accumulation of storage carbohydrates. Importantly, yeast cells in stationary phase are metabolically active, derive energy from aerobic respiration, and remain responsive to environmental signals. Thus, stationary phase is similar to the G0 phase in non-dividing cells that age chronologically in human tissues.
Yeast divide asymmetrically. A larger “mother” cell gives rise to a smaller “daughter” cell through a budding process (rather than cell fission). For most strains of yeast, mother cells typically divide less than 40 times (i.e., mother cells typically give rise to fewer than 40 daughter cells). Thus, replicative aging limits the number of daughter cells formed by a mother cell.
|2005‑7||NIH R21||Regulation of Yeast Life Span||PI|
|2002‑3||Ellison Medical Foundation||Extrachromosomal rDNA Circles: More Than Episomes with Origins?||PI|
|2000‑2||American Cancer Society, Florida Division||Nucleolar Function and Cell Growth in Yeast||PI|
|1994‑99||NIH R01||Nucleolar Function and Cell Growth in Yeast||PI|
Aris,* JP, AL Alvers, RA Ferraiuolo, LK Fishwick, A Hanvivatpong, D Hu, C Kirlew, MT Leonard, KJ Losin, M Marraffini, AY Seo, V Swanberg, JL Westcott, MS Wood, C Leeuwenburgh, and WA Dunn, Jr. 2013 Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast. Exp. Gerontology In press. PubMed | Journal
Aris, JP, LK Fishwick, ML Marraffini, AY Seo, C Leeuwenburgh, and WA Dunn, Jr. 2012. Amino Acid Homeostasis and Chronological Longevity in Saccharomyces cerevisiae. In Aging Research in Yeast. M Brietenbach, P Laun, SM Jazwinski, Eds. Springer, NY. Subcell Biochem. 57:161-86. PubMed | Journal
Aris, JP, MC Elios, E Bimstein, SM Wallet, S Cha, KN Lakshmyya, and J Katz. 2010. Gingival RAGE expression in calorie restricted versus ad libitum fed rats. J Periodontology 81:1481-7. PubMed | Journal
Falcon, AA, S Chen, MS Wood, and JP Aris. 2010. Acetyl-coenzyme A synthetase 2 is a nuclear protein required for replicative longevity in Saccharomyces cerevisiae. Mol Cell Biochem. 333:99-108. PubMed | Journal
Alvers, AL, LK Fishwick, MS Wood, D Hu, HS Chung, WA Dunn, Jr, and JP Aris. 2009. Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell 8:353-359. PubMed | Journal
Pafundi, D, C Lee, . Watchman, V Bourke, J Aris, N Shagina, J Harrison, T Fell, and W Bolch. An image-based skeletal tissue model for the ICRP reference newborn. 2009. Phys Med Biol 54:4497-531. PubMed | Journal
Bhabhra, R, DL Richie, HS Kim, WC Nierman, J Fortwendel, JP Aris, JC Rhodes, and DS Askew. 2008. Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus. Eukaryotic Cell 7:575-583. PubMed | Journal
Swanson, MS, and JP Aris. 2008. Post-transcriptional control: nuclear RNA processing. In Inborn errors of development. Second Edition. CJ Epstein, RP Erickson, A Wynshaw-Boris, Eds. Oxford University Press. Oxford, UK. pp1108-1125. Library of Congress
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Major Teaching Responsibilities
College of Medicine
Foundations of Medicine (BMS 6031)
Director of lecture and laboratory course for first year medical students.
Course web page: Foundations of Medicine
College of Dentistry
Developmental Biology and Psychosocial Issues Over the Life Span (DEN 5210)
Director of human embryology module consisting of nine lectures, one review session, and one exam.
Medical Sciences Senior Research (BMS 4905)
Mentor for undergraduate students conducting experiments to explore cellular mechanisms of aging.