Biology of Aging
About the Course
The aim of the course is to introduce students to the latest knowledge in the field of biology of aging. Course is about molecular mechanisms that control cell growth, which normally ends with cellular aging, but also the phenomenon of carcinogenesis resulting from the changes of the same molecular structures. Students will get an overview of modern approaches and techniques to this research from the cellular level to the organism and population level. Special attention will be paid to molecular mechanisms of tissue aging and mechanisms of aging in transgenic model organisms, the beginning and development of diseases associated with the aging process etc.
Lectures:
Introduction to Molecular biology of aging. Definitions, origins of research on molecular mechanisms of cellular aging, overview of modern ideas and techniques of aging research from cell to organism.
Cellular aging. Hayflick experiment, a model of human and mouse fibroblasts, endothelial and epithelial cells, the morphological and physiological changes in senescent cells.
Molecular basis of (patho)physiology of cellular aging, mechanisms of genetic control of cellular aging: the role of telomeres, structure and mechanisms of their shortening, the role of cell cycle control in aging and telomere shortening.
Subtelomeric sequences, their structure and impact on telomeres, types of subtelomeric sequences in several model organism (mammals, yeast, Drosophila, nematodes).
Telomeric proteins and their interactions with telomeres; shelterin, recombinant proteins at telomeres, mutations of telomeric proteins associated with genetic diseases.
Telomerase; structure of their genes and nucleoprotein, 3D structure, mechanisms of action, interactions with telomeres.
Molecular basis of (patho)physiology of aging of tissues and organs, genetic and epigenetic mechanisms of aging control in mice (knock out experiments, histological analysis), the skin as a model: aging of fibroblasts, melanocytes, keratinocytes, endothelial cells, microvasculature.
Aging at the organismal level, accumulation of senescent cells, their effect on the surrounding tissue, changes in extracellular matrix and signal molecules - physiological profile of inflammation.
Population studies of aging, survival, morbidity and mortality, telomeres as a predictive factor for the individual and population aging, population dynamics of aging in Croatia.
Free radicals, their formation, propagation and neutralization, the cell damage theory and energy metabolism, oxidative stress in cell senescence: hyper or hypoxia, telomeres and oxidative stress, the role of mitochondria in cell damage and cellular aging, the role of antioxidants and stress response mechanisms in cell aging.
Tissue damage related to aging, protein modifications, antioxidant mechanisms and protection from damage (enzymes, small molecules vitamins, minerals).
Caloric restriction, model organisms (mouse, rat, monkey, Drosophila), a longitudinal study of calorie restriction in monkeys (Macaca mulatta ) for 25 years, the impact of diet on aging and mortality. Carcinogenesis, M1/M2 mechanism, cell crisis and immortalization, effect of SV40 large T antigen (Tg), the role of p53 and pRb ALT alternatively lengthening of telomeres in carcinogenesis and metabolism of unicellular organisms, impact on the stability of telomeres.
Evolutionary theories of aging and relationship of aging with carcinogenesis. Comparative biology of aging describe specifics of some groups of organisms (higher mammals, primates, birds, reptiles, insects, aquatic organisms), the role of telomeres and telomerase in aging of various organisms, absence or neglected aging in some organisms . Aging of non-regenerative organs and tissues (brain and nervous system, myocardium) and their resistance to stress, the molecular mechanisms of some degenerative diseases associated with aging; Alzheimer's, Werner's syndrome, Hutchinson Gilford syndrome progeria).
Learning outcomes
During this course (15 x 2 + 1 hours), participants will gain the latest knowledge in the field of molecular biology of aging, particularly the molecular mechanisms controlling the limited growth of normal cells and their impact on the surrounding tissue and aging at the level of the organism, including the nervous system, about mechanisms of aging of few model organisms through which will be explained the importance of genetic control of aging and the impact of cellular damage on individual aging and population studies as well as evolutionary theories of aging.
Students are required to attend and participate in teaching through listening to lectures, preparation and presentation of seminars and participation in discussions.
1 ) Upon completion of the course, students must acquire knowledge about the biology of aging according to the presented content and they must acquire critical thinking.
2 ) Students must logically connect the molecular mechanisms of cellular aging with aging at the level of the organism as well as various environmental influences that also can change the dynamics of aging.
3 ) They must connect the interrelationship between telomere metabolism, mitochondrial metabolism and free radicals in aging and the development of various diseases associated with aging.
4 ) They must acquire knowledge from various lectures and be able to connect it in understanding of the transition of normal cells to a tumor where same molecular mechanisms in one case provide limited cell growth, and in another case cell immortalization.
5 ) Gaining knowledge about free radicals, caloric restriction diet and telomere metabolism students will be able to have a critical view on todays widespread application of antioxidants and various diets that attempt to slow aging process.
Final seminar
Critical analysis of a scientific article related to the course.
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- Handbook of the Biology of Aging. Third edition. Editors: Schneider, E. L. and Rowe, J. W., Academic Press, Inc. San Diego, California, 1990.
Nature, vol. 408, No. 9 (2000), 233-269. Skup preglednih članaka.
Oncogene, vol. 21, No. 4 (2002), 493-697. Skup preglednih članaka.
Science, vol. 273, No. 5271 (1996), 1-148. Skup preglednih članaka.
- Kim, S., Jiang, J. C., Kirchman, P. A., Rubelj, I., Helm, E. G. and Jazwinski, S. M.: Cellular and molecular aging. in Comprehensive Geriatric Oncology, second edition, (L. Balducci, W. B. Ershler, G. H. Lyman, eds.) Harwood Academic Publishers, Amsterdam, 1998. pp. 123-155.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O. M., Peacocke, M. and Campisi, J.: A biomarker that identifies senescent human cells in culture and in aging skin in vivo, Proc. Natl. Acad. Sci. USA, 1995; 92: 9363-9367.
Blasco M. A. mouse models to study the role of telomeres in cancer, aging and dna repair [Review]. European Journal of Cancer. 38(17): 2222-2228, 2002 Nov.
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