Epigenetic regulation of genes associated with aging

다국어 초록 (Multilingual Abstract)

Epigenetic regulation of genes associated
with aging

Kang, Gil Myoung
Department of Biochemistry and Molecular Cell Biology
College of Pharmacy, Sungkyunkwan University

Aging is arguably the most familiar yet least well-understood aspect of human biology. Each of us quickly acquires knowledge of the aging process, first by observing what it does to others and then by experiencing its effects ourselves. Most can offer some kind of theory as to why aging exists and how it is caused. Some of the major theories that have been proposed to explain aging are the following: free radical theory, genetic program theory, molecular inflammation theory, cross-linking theory and immunological theory.
One theory of aging proposes that ROS which are generated by metabolism cause cumulative damage over a lifetime. One category of study that is supportive of this view involves animals transgenic for genes encoding antioxidants. A more recent study shows that expression of human SOD1 exclusively in Drosophila adult motor neurons leads to a 40% extension in life span. In addition to ROS theory, epigenetic collapses such as, dys-regulations of DNA methylations or histone modifications is also closely related to the aging. The nature of the age-related change in DNA methylations or histone modifications, however, is not well understood yet. So I examined the expression pattern of aging related genes SOD and epigenetic modifying enzymes (DNMTs, HDACs and protein methyltransferases) in rat brain tissues (6 month, 12 month and 24 month). There are no significant changes in SOD, DNMTs and class I HDACs. But I found that expression of HDAC4, HDAC5, HDAC6 were increased in aging rat brain tissue and PRMT1, CARM1 were also significantly increased in aging rat brain tissue. These global increases of enzymes may be closely associated with the aging.
For all related to aging approaches, from in vitro molecular studies to clinical trials, contributions of cell and molecular biology are crucial and offer the prospect of therapeutic advances that address fundamental biological processes as well as the clinically important challenges of aging.

목차 (Table of Contents)

• I. Abstract 1
• II. Introduction 4
• III. Materials and methods 11
• 1.Tissue and RNA preparation 11
• 2.RT-PCR and Real-time PCR 11
• 3. Western blot analysis 13
• IV. Results 14
• 1.Expression level of SOD in aging rat tissue 14
• 2.Expression level of epigenetic markers (HDAC family)in aging rat brain tissue 16
• 3.Expression level of protein methytransferase family (lysine methytransferase) 19
• 4.Expression level of protein methytransferase family (arginine methytransferase) 21
• V. Discussion 24
• VI. Reference 27
• VII.국문요약 35