LECTURE-1 - Theories of Aging Christiaan Leeuwenburgh Ph.D...

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Theories of Aging Christiaan Leeuwenburgh, Ph.D. Christiaan Leeuwenburgh, Ph.D. Biochemistry of Aging Laboratory Web Page: http://grove.ufl.edu/~cleeuwen/ University of Florida University of Florida Biochemistry of Aging Course 2003 Lecture 1 Lecture 1 Aging: Progressive Universal Post-maturation Irreversible? Senescence: Deleterious Aging Age-related diseases: are the clinical manifestations of senescence What is Aging? Leading Causes of Death 1900; 1) pneumonia, tuberculosis 2) GI infections, diarrhea 3) heart disease 1988; 1) heart disease, 2) cancer, 3) neurodegenerative diseases 4) sarcopenia Weindruch Jeanne Louise Calment was born in Arles, France on February 21, 1875. She once met Vincent Van Gogh in her father's shop. Her genes may have contributed to her longevity as her father lived to the age of 94 and her mother to the age of 86 . She married a distant cousin at the age of 21. Her only grandson died in 1963. She rode a bicycle to the age of 100. Jeanne Calment 122 Years February 21,1875 August 4,1997 Maximum Life-span Mean Life-Span • Maximum life-span (between species and maybe within) is mostly genetically determined (MLSP) • Mean life-span is influenced by the environment, disease, and life-style (MLS) General Objectives What is the objective of The National Institute on Aging The National Institute on Aging and various groups investigating mechanisms of aging and strategies for healthy aging. –Improved understanding of the mechanisms of longevity can be used to fight age-related diseases and disabilities to ensure a healthy, active, and independent life well into very old age
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Molecular Gene Theories Codon restriction - Fidelity/accuracy of mRNA translation is impaired due to inability to decode codons in mRNA. Error catastrophe - Fidelity of gene expression declines with age, resulting in increased fraction of abnormal proteins. Somatic mutation - Accumulation of molecular damage, primarily to DNA/genetic material. Dysdifferentiation - Gradual accumulation of random molecular damage impairs regulation of gene expression. Gene regulation - Aging caused by changes in gene expression regulating both aging and development. Gene expression protein folding and activity Cellular Theories •F r e e r a d i c a l - Oxidative metabolism produces highly reactive free radicals that subsequently damage protein and DNA. Mitochondrial DNA Damage • Wear and tear - Accumulation of normal injury – Glycoxidation Theory of Aging (products from glucose with proteins + oxidation; AGE (advanced glycation End- products – Inflammation Theory of Aging • Apoptosis - Programmed cell death resulting from intrinsic damage and genetically determined events or genome crisis. • Senescence - Phenotypes of aging are caused by an increase in frequency of senescent cells. Senescence may be the result of telomere loss (replicative senescence) or cell stress (cellular senescence).
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This note was uploaded on 05/19/2011 for the course BCH 3218 taught by Professor Johnsteward during the Fall '08 term at University of Florida.

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LECTURE-1 - Theories of Aging Christiaan Leeuwenburgh Ph.D...

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