During aging, many biological processes go out of balance. Changes are apparent at the level of the whole animal, tissues, cells, molecules, and metabolism. We believe that changes at the molecular level drive the changes at higher levels. Animals have extensive endogenous mechanisms that maintain balance (homeostasis) in young animals. These homeostatic mechanisms degrade with age. We believe that we can prevent this degradation and re-engage these maintenance systems in older animals, which will prevent disease and extend lifespan.
The Lithgow lab concentrates on identifying small drug-like molecules that re-engage and enhance homeostatic mechanisms in the microscopic nematode worm C. elegans. We aim to boost mechanisms that prevent protein misfolding and remove damaged proteins and other forms of molecular damage. Frequently, treatment with such molecules results in lifespan extension and postpones disease pathology. We now collaborate with other Buck researchers to test the effectiveness of these compounds to prevent chronic disease in mouse models.
Why it matters
Aging mechanisms are novel targets for both proliferative diseases such as cancer and degenerative diseases such as Alzheimer’s. The characterization of normal aging mechanisms is vital for the development of new therapeutic avenues for these devastating conditions. Aging mechanisms discovered in the worm model are very likely to be important in humans as well and may influence drug discovery. We also believe that demonstrating the effectiveness and mechanisms of non-drug interventions like nutrients and diet may provide information for people to make lifestyle choices to help them live better longer.
One theme continues to emerge from our work – that aging and disease stem from common mechanisms. Delaying disease by delaying the aging process is a real proposition.
Gordon Lithgow, PhD
A native of Scotland, Dr. Lithgow received his PhD from the University of Glasgow and obtained further training at Ciba Geigy AG in Basel, Switzerland, and at the University of Colorado. He established his lab studying the biology of aging at the University of Manchester, England, before moving it to the Buck Institute in 2000.
Dr. Lithgow has been recognized for his research with a Glenn Award for Research in Biological Mechanisms of Aging, a senior scholarship from the Ellison Medical Foundation, and the Tenovus Award for Biomedical Research. He has served on many national advisory panels in both the United Kingdom and the United States, including the National Institute on Aging’s Board of Scientific Councilors, and has served as the chair of biological sciences at the Gerontology Society of America.
Dr. Lithgow has partnered with a series of biotechnology companies in sponsored research agreements and has strong collaborations in preclinical aging research on diseases such as osteoporosis and Parkinson’s disease.
Suzanne Angeli, PhD Research Scientist
Dr. Angeli received her bachelor’s degree in cell and molecular biology from Tulane University in New Orleans, Louisiana, in 2003. She went on to study protein misfolding in Huntington’s disease in the laboratory of Dr. Marc Diamond at University of California San Francisco and completed her PhD in 2010. For her postdoctoral work, Dr. Angeli joined the Andersen lab to study models of Parkinson’s disease and manganese toxicity in C. elegans. She continued her postdoctoral studies in the Lithgow lab, where she is studying the mitochondrial unfolded protein response (UPR) in C. elegans.
Dipa Bhaumik, PhD Staff Scientist, Lab Manager
Dr. Bhaumik completed her PhD in biochemistry at the University of Calcutta, India. Prior to coming to the Buck Institute, she held fellowships at the University of North Carolina at Chapel Hill, Stanford University, Calcutta University, and the University of Pennsylvania. Dipa's primary job in the Lithgow lab is to manage the lab and assist in the research of other lab members. Her own research project involves testing the effects of different natural products on C. elegans’ lifespan and developing C. elegans models of age-associated neurodegenerative disease.
Manish Chamoli, PhD Larry L. Hillblom Postdoctoral Research Fellow
Dr. Chamoli earned his PhD in aging biology in June 2015 from the National Institute of Immunology in India after completing a five-year integrated master’s in biotechnology. His PhD work was focused on understanding molecular pathways mediating dietary restriction–induced longevity using C. elegans as a model organism. His research was supported by a fellowship from the Indian government’s Department of Biotechnology. Manish joined the Lithgow lab as a postdoctoral fellow in February 2015. He is now working in collaboration with the Andersen lab to utilize novel pharmacological agents to understand the role of autophagic processes in aging and age-related neurodegeneration. His current work is supported by a three-year postdoctoral fellowship from the Larry L. Hillblom Foundation.
Anna Foulger Research Associate
Anna joined the Lithgow lab in 2014. She was a vital member of the Caenorhabditis Intervention Testing Program (CITP) for years and is now assisting Suzanne Angeli with her project. Anna is an author on the paper “Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects,” published in Nature Communications. She plans on getting more experience with mice and cells in the near future. Anna graduated magna cum laude with a bachelor’s degree in zoology from San Francisco State University in May 2018.
Angelina Holcom PhD Candidate, USC-Buck Biology of Aging Program
Angela received her bachelor's degree in biology from the University of Hawaii at Mānoa.
Todd Plummer Research Associate II, CITP Project Coordinator
Todd joined the Lithgow lab in 2014 after working in the Buck Institute's Resource Development Department as the manager of the Buck Advisory Council for three years. Todd manages the lab's experiments for the Caenorhabditis Intervention Testing Program (CITP), an NIH-funded consortium project with two other institutions. The project focuses on uncovering pharmacological interventions that extend healthspan and lifespan in the C. elegans model system and also examines the problem of reproducibility in science by focusing on strict adherence to experimental methods, regular communication among consortium members, and managing environmental variables.
Minna Schmidt PhD Candidate, USC-Buck Biology of Aging Program
Minna graduated from Lowell High School in San Francisco as an AP honors student in chemistry and physics. After completing a year at City College of San Francisco, she attended Brandeis University, where she received a bachelor’s degree with honors in chemical biology in 2013. She completed a master’s degree in chemistry at the University of California, Santa Cruz, in 2015. Minna is currently pursuing characterization of novel small chemical compounds that act to prevent neuronal cell loss associated with Parkinson’s disease in particular inducers of hypoxia inducible factor 1 alpha (HIF1alpha), which previous publications from the Andersen lab have suggested serve a neuroprotective role in the disease.
Azar Asadi Shahmirzadi PhD Candidate, USC-Buck Biology of Aging Program
Azar is a graduate student currently working in the Lithgow Lab focused on pharmacological interventions for delaying aging and age associated diseases. She is from Iran and received her Doctor of Pharmacy degree from Tehran University of Medical Sciences (Tehran, Iran) in 2011. She worked as a pharmacist for few years and became interested in aging process, one of the biggest challenges in health. In 2014, she moved to the United states to start her Ph.D. in Biology of Aging at University of Southern California, the world’s first and only Ph.D. program completely devoted to Aging studies.
Renuka Sivapatham Postdoctoral Research Fellow
Renuka is receiving her PhD in neurobiology from the University of Southern Denmark in summer 2018. Her PhD studies were focused on modeling Parkinson’s disease using patient-specific and isogenic induced pluripotent stem cells (iPSC). She joined the Lithgow and Andersen labs in 2017. Her proficiency in developing methods for the therapeutic application of iPSCs in Parkinson’s disease have furthered her interest in pursuing translational research in neurodegenerative diseases, including Alzheimer’s disease. Her research focuses on studying protein homeostasis during the development of Alzheimer’s disease in the nematode C. elegans and rodent models.
- Melov, S., Ravenscroft, J., Malik, S., Gill, M. S., Walker, D., Clayton, P., Wallace, D., Malfroy, B., Doctrow, S., Lithgow, G. J. (2000 Sep 1). Extension of lifespan with superoxide dismutase/catalase mimetics. Science, 289, 1567–9. PubMed PMID: 10968795.
- Jenkins, N. L., McColl, G., Walker, D. W., Harris, J., Lithgow, G. J. (2000 May 18). Evolution of C. elegans lifespan. Nature, 405, 296–7. DOI: 10.1038/35012693. PubMed PMID: 10830948.
- Olsen, A., Vantipalli, M. C., Lithgow, G. J. (2006 Jun 2). Checkpoint proteins regulate survival of the post-mitotic adult soma in Caenorhabditis elegans. Science, 312, 1381–85. DOI: 10.1126/science.1124981. PubMed PMID: 16741121.
- Alavez, S., Vantipalli, M. C., Zucker, D. J. S., Klang, I., Lithgow, G. J. (2011 Apr 14). Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature, 472, 2326-9. DOI:1038/nature09873. PubMed PMID: 21451522.
- Lucanic, M., Held, J. M., Vantipalli, M. C., Klang, I. M., Graham, J. B., Gibson, B. W., Lithgow, G. J., Gill, M. S. (2011 May 12). N-acylethanolamine signaling mediates the effect of diet on lifespan in C. elegans. Nature, 473 226–9. DOI: 1038/nature10007. PubMed PMID: 21562563.
- Siddiqui, A., Bhaumik, D., Chinta, S. J., Rane, A., Rajagopalan, S., Lieu, C. A., Lithgow, G. J., Andersen, J. K. (2015 Sep 16). Mitochondrial quality control via the PGC1α-TFEB signaling pathway is compromised by parkin Q311X mutation but independently restored by rapamycin. J Neuroscience, 16, 12833–44. DOI: 10.1523/JNEUROSCI.0109-15.2015. PubMed PMID: 26377470.
- Mark, K. A., Dumas, K. J., Bhaumik, D., Schilling, B., Davis, S., Oron, T. R., Sorensen, D. J., Lucanic, M., Brem, R. B., Melov, S., Ramanathan, A., Gibson, B. W., Lithgow, G. J. (2016 Oct 25). Vitamin D promotes protein homeostasis and longevity via the stress response pathway genes skn-1, ire-1, and xbp-1. Cell Reports, 17, 1227–1237. DOI: 10.1016/j.celrep.2016.09.086. PubMed PMID: 27783938.
- Lucanic, M., et al. (2017 Feb 21). Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects. Nature Communications, 8, 14256.