SPEC COURSE INTRO TO NEUROSCIENCE
SPEC COURSE INTRO TO NEUROSCIENCE A&S 300
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This 7 page Class Notes was uploaded by Noah Wyman on Friday October 23, 2015. The Class Notes belongs to A&S 300 at University of Kentucky taught by Staff in Fall. Since its upload, it has received 10 views. For similar materials see /class/228228/a-s-300-university-of-kentucky in Arts and Sciences at University of Kentucky.
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Date Created: 10/23/15
Diseases of aging There is still no cure for the common birthday John Glenn Assigned reading Chapter 8 Handbook of Aging 5th ed Aamp8300002 Jim Lund Diseases of Aging Cancer Heart disease Cerebrovascular disease Arthritis Osteoporosis Neurodegenerative disease Diabetes Type II Cancer 0 One third of people suffer from some form of cancer 0 20 of all deaths are cancer related 0 In developed countries cancer care represents about 10 of total health care costs What is cancer A lineage of cells in which normal genetic control of cell proliferation and cell death have been disrupted Cancertypes Carcinomas in which tumors arise in epithelial tissues 0 Sarcomas in which tumor arises in mesenchymal tissue 0 Hematopoeitic amp lymphoid malignancies Cancer type by age females vuiuqu Annuui mummu milmummy mmquot mm Hmleu Lulan and ltl39vim w lluutnl r I my W I mu l illu m mun m u w w w H N u nu w m av mumm lylullnl Cancer type by age males rinuil humming m H mm A u i Wm m wan m lw x mm mi i 39 i n Cancertypes 0 Which cancer type is common varies from species to species and is often sexdependent 0 Human males prostate cancer 0 Females breast cancer Evolution of LongLived Organisms LIFE SPAN Sl39lgl we bd Mumcellular Mumcellular Post Postmitotic mitotic Renewable ORGAN ISMS CELL DIVISION IS RISKYII Cancer The good news Genes evolved to protect from cancer tumor suppressor genes Tumor suppressor genes cause damaged cells to die or arrest growth undergo apoptosis or senescence Apoptosis and senescence cell populations can t replenish A Cancer The bad news Cancer risk rises exponentially with age Fueled by somatic mutations Mutations caused by DNA damage from endogenous and exogenous sources Cellular Senescence Arrests Cell Growth In Response to Potential CancerCausing Events Chromatin Instability Stressdamage IrreverSIble Signals arrest of Damage Oncogenes Shortdysfunctional telomeres First description the Hay ick limit b 396 m o 398 3 In nite E Replicative g Life Span E quotImmortalquot 0 Number of cell divisions EX CE P Tl ON 8 errn ine Eary embryonic cells stem cells Many tumor cells What happens when cells exhaust their replicative life span Genetic causes of cancer Mutations to oncogenes signalling pathways influencing death and proliferation Ras Bcl 2 Mutations to DNA repair genes mismatch repair etc Mutations to tumor suppresor genes gt50 P53 p16 Inactivation of tumor suppressor genes encoding p53 and pRB proteins most common What are oncogenes Genes involved in cell growth and development growth factors growth factor receptors etc When mutated are often called protooncogenes Often related to viral oncogenes eg src oncogene in retroviruses Often highly conserved eg ras found in both humans and yeast Mutations have a dominant phenotype and many are often required Mutations can be both point bladder carcinoma and chromosomal translocation chronic leukemia A What are Tumor suppresors Genes whose products block abnormal growth Mutations are recessive both alleles must be lost for loss of function The two hit model of cancer progression Knudsen 1971 explains both hereditary and sporadic cases In hereditary case 1 mutation is in germ line and 2nd in soma Eg retinoblastoma Loss of TS genes often leads to several different types of cancer 50 of cancers have lost P53 TS genes are redundant until some other form of genetic damage arises Tumor Progression by Clonal Evolution Cancer cells are at a short term growth advantage over wild type cells Thus selection should lead to a preponderance of cancer cells over healthy cells As more mutations accumulate in cancer cells the greater the competitive edge However at the whole body level there is a cost In other words cancer evolves towards higher virulence within the body Mendelian Cancers 50 Mendelian disorders associated with high cancer risk In these cases there are multiple primary tumors unlike sporadic Retinoblastoma 120000 Mutation to RB l 13d through germline Each eye must then accumulate somatic mutation RB l mutations leads to loss of heterozygosity homozygosity observed around region of gene Evolution the case of colorectal cancer RAS mutation A Tumor Progression by Clonal 5q m utatio n Chromosomal loss Multiple hit model 36 mutations required for tumorgenicity A Cancer is a genetic disease Cancer cells are altered self by virtue of aberrant gene expression As a result of this Cancer cells contain proteins not found in normal cells or not expressed at high levels in normal cells or only expressed in normal cells at certain stages of development b Natural selection a immune elraclory liana lype In fact Genomic instability an The immune response is mostly successful p 2 Cellular uansierl o lumorvananls E eclivn w Immunclherapy g d Active vaccmzmun or natural salnclion a 339 am lIv 39 but Tumours escape from the immune response Khong ampResu39fo 2002 yr Antigen loss So if cancer is immunogenic quot and immunosurveillance a mm mm rearm 13335 L eXIsts ltgt g d i 39 tumor quot a quot s Why does cancer occur m Why is the immune response not successful 0 may be procarcinogenic from 5 yr old 39 25X10395 mutationsbp in lymphocytes from 80 yr old Opposne effeCts39 0 from Martin etal 1996 0 Tumor angiogenesrs Impaired In older animals 0 This works out to about 100 mutant genes per cell at old age Other a erelated chan es g g l Somatic DNA mutation contribute to cancer Weakened barriers basal membranes Mutation rate goes up with age Tissue changes due to senescent cells 39 5x105 mutationspp in lymphocytes Diseases of Aging Effect on mean lifespan Cancer Heart disease Cerebrovascular disease Arthritis Osteoporosis Neurodegenerative disease Diabetes Type ll 0 Curing cancer 2 years to average human lifespan Curing heart disease 34 years to average human lifespan Cure all diseasegtperhaps add 15 years to human life expectancy