TRACT GASTROINTESTINAL Aging and. What IS Aging?

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  • Slide 1
  • TRACT GASTROINTESTINAL Aging and
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  • What IS Aging?
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  • Practically . Aging = reduced tissue/physiological function Aging = increased susceptibility to disease (age-related diseases) Aging = decreased resistance to stress (physical and psychological)
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  • Why do we age --- GENES Genes determine species-specific life span (LAGs) (e.g., mice, monkeys, humans, tortoises) Genes determine differences among individuals within a species (e.g., big/small noses) (genetic polymorphisms)
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  • Species-specific longevity genes Flies ( Drosophila melanogaster ) Nematodes ( Caenorhabditis elegans ) Mice ( Mus musculus ) Humans ( Homo sapiens ) Galapagos turtles ( Geochelone elephantopus) Life spans ranging from 2-3 weeks to 100-200 years!
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  • AGE (log) Fitness Disease (Cancer, osteoporosis, diabetes, etc.) AGING in MICE AND MEN 18 Months 50 Years MICE HUMANS Mice and Humans are 97% genetically similar!
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  • Species-specific longevity genes Potentially big pay-off, but complicated by development/evolution What are the genes that determine why mice live 100 years?
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  • Individual longevity genes (polymorphisms) Smaller pay-off, but possibly amenable to intervention (environment, life style, drugs??)
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  • Aging Can we do Intervention.?
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  • DIET Eat well, but not too much! FOOD ---> ENERGY Oxygen metabolism ----> damaging byproducts (ROS, oxidative stress) OPTIMAL food = less ROS, less damage, more defenses longer lifespans! Anti-oxidant defenses good, but not perfect (different among species) Food ----> simple molecules + oxygen (mitochondria) ----> energy
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  • DIET CALORIC RESTRICTION GOOD NEWS! 30-40% calorie restriction without malnutrition extends HEALTHY lifespan 40-50% (worms, flies, mice, rats -- maybe monkeys) BAD NEWS! Life SEEMS longer!! (let's develop that CR pill) DIET
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  • EXERCISE Yes, yes, yes .. (but not too much) Exercise ---> healthier muscles, May be prevent telomere shortening.greater fitness Greater protection from oxidative stress! (not such a paradox, anti-oxidant defenses)
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  • Think good thoughts! Avoid undue stress Physiological stress: Stress hormones, a double edged sword Physical stress: Overwhelm cellular defense mechanisms
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  • Why do we age --- PAST ENVIRONMENT Genes evolve in response to environment This is REALLY why we age!
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  • Aging before cell phones .. 100% SURVIVORS AGE "Natural" Environment (hazards, predators, infection, etc.) 80 yrs 3-4 yrs "Protected" Environment (climate control, biomedical intervention etc.) 40 yrsHUMANS: 4 mosMICE:
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  • GOOD NEWS! If we keep our "protected" environment, we WILL evolve longer life spans! BAD NEWS! It's going to take a LONG time!
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  • Sooo. What's to be done about aging now? Optimize present environment New therapies on the horizon! Cell based therapies Drug based therapies Support basic research in aging!
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  • Individual longevity genes Healthy centenarian studies are underway! Solution = preventive drugs Solution = ?????? Most identified so far are disease-susceptibility genes its role in several biological processes not directly related to lipoprotein transport, including Alzheimer's disease (AD), immunoregulation, and cognition.(e.g., ApoE4)Alzheimer's diseaseimmunoregulationcognition
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  • Cell based therapies Stem cells! embryonic adult nuclear transplant (cloning) Telomerase! increase cell divisions anti-cancer therapy
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  • Drug-based therapies Anti-oxidants, mitochondrial protectors, etc. Hormones! growth hormone insulin/IGF (lessons from worms and flies) estrogen CR mimetics!
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  • Elizabet Blackburn Physiology nobel prize Winner 2009
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  • We can determine How long We Live!!?
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  • Future Re search
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  • Aging Definition Aging is the progressive, universal decline first in functional reserve and then in function that occurs in organisms over Aging is heterogeneous. It varies widely in different individuals and in different organs within a particular individual. Aging is not a disease; however, the risk of developing disease is increased, often dramatically, as a function of age. The biochemical composition of tissues changes with age; physiologic capacity decreases, the ability to maintain homeostasis in adapting to stressors declines, and vulnerability to disease processes increases with age.
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  • Biology of Aging As we age, we become increasingly unlike one another. For any variable one can measure, the variation in the distribution of values in a population increases with age. While the mean value may trend up or down, the age-related increase in the range of values is striking testimony to the diverse manifestations of the aging process. In addition, homeostatic mechanisms are slower to respond to stressors and take longer to restore normal function as we age. The ability to maintain stable function in the face of a change in the environment is called allostasis and it declines with age.
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  • Demography of Aging Improvements in environmental (e.g., clean water and improved sanitation) and behavioral (nutrition, reduced risk exposures) factors and the treatment and prevention of infectious diseases are largely responsible for the 30- year increase in life expectancy since 1900. In the United States, by 2030, 1 person in 5 will be >65 years.
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  • Global Aging At present 59% of older adults live in the developing countries of Africa, Asia, Latin America, the Caribbean, and Oceania. The developed world has the largest absolute number of older adults and is experiencing the largest percentage increase.
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  • Gastrointestinal Disorders Gastrointestinal (GI) disorders represent the third cause of consultations by general practitioners among subjects older than 65 years in Western countries.
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  • Gastrointestinal Disorders Age-related anatomical and physiologic changes occur in the major organ systems, affecting functions as diverse as swallowing and hepatic and renal clearance of therapeutic drugs. Because of these factors, and because older patients are more likely to be receiving multiple drugs for concomitant illness, they are more prone to drug-drug interactions and to medication-induced injury of the esophagus and stomach. In addition, several gastrointestinal disorders, notably gastroesophageal reflux and peptic ulcer disease, are commonly seen in the elderly. J Clin Gastroenterol. 1991;13 Suppl 2:S65-75Bozymski EM, Isaacs KLBozymski EM Department of Medicine, University of North Carolina, Chapel Hill 27599-7080
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  • Objectives Define age-related changes in the gastrointestinal tract Discuss common G.I. problems associated with aging Describe the risk factors for gastro- esophageal reflux disease Describe the risk factors for peptic ulcer development List the causes of diarrhea and fecal incontinence in the elderly
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  • Epidemiology Over 35 million people aged > 65 years in the United States 12% of the 2003 US population were older than 65 18.3 million aged 65-74 12.9 million aged 75-84 4.7 million aged 85 35% to 40% of geriatric patients will have at least 1 GI symptom in any year Common problems in this age group include constipation, fecal incontinence, diarrhea, irritable bowel syndrome (IBS), reflux disease, and swallowing disorders Hall KE, et al. Gastroenterology. 2005;129:1305-1338. He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06. Hall KE, et al. Gastroenterology. 2005;129:1305-1338. He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.
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  • The Age Wave Year Population Increase in the Number of Persons Aged 65+ Years in the United States Increase in the Number of Persons Aged 65+ Years in the United States Number (millions) Percent of population Number (millions) Percent of population 3 (4%) 5 (5%) 9 (7%) 17 (9%) 26 (11%) 31 (13%) 35 (12%) 40 (13%) 55 (16%) 72 (20%) 4 (4%) 7 (5%) 12 (8%) 20 (10%) He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.
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  • Motility an GI tract Normal aging is associated with significant changes in the function of most organs and tissues. In this regard, the gastrointestinal More important is the impact of various age-related diseases on gastrointestinal motility in t