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변화에개인차가크게나타남 - 20주간의운동프로그램에따른 VO2max 변화없거나아주낮은증가를보임 ( 일부참가자 ) - but 평균적으로는분당 400ml 증가하였다고보고함 - 결국모든사람이운동후 VO2max가증가할수있다는오류 결론적으로 -

1 노화와운동과유전체 변재종 우송대학교 운동유전체학 (Kinesiogenomics) 운동과신체활동처방과관련된유전학 운동생리학분야의연구결과는평균으로보고됨 각개인의운동반응과적응수준의다양성을설명하지못하는한계가있음 영역 : 운동훈련에대한다양한유전자표현형에따른운동반응성확인 적용 : 질환위험인자개선및스포츠수행능력을향상시키기위한최적의운동중재수단연구 Bouchard 등 (1999) HERITAGE Family Study - 운동훈련에따른 VO2max 변화에개인차가크게나타남 - 20주간의운동프로그램에따른 VO2max 변화없거나아주낮은증가를보임 ( 일부참가자 ) - but 평균적으로는분당 400ml 증가하였다고보고함 - 결국모든사람이운동후 VO2max가증가할수있다는오류 결론적으로 - 운동으로인한신체의반응 & 적응현상 개인별로다양하게나타남 연구결과를평균치로나타내는것은비논리적임 Bouchard & Rankinen(2001) - 유산소운동에의해나타나는 BP, HR, HDL-c 변화 개인차가크게나타남 개인차를설명하기위한 3가지요인 실험적오류, 환경적요소, 유전적요인 87

2 대한임상건강증진학회 2014 추계학술대회 연구성과요약 개인차설명시고려할중요한요인 운동유전체학분야의발전은다른유전체학의발전과마찬가지로인간게놈염기서열이일반화되기시작한시점인 2000년이후가속화됨 1) 실험적오류 2) 환경적요소 과학기술및실험기술의발달 ~2000 년 2000 년 ~2005 년 3) 유전적요인 운동에대한반응의개인차를설명할유일한요소 향후운동과학및건강에기여할것으로기대되는유전학의역할 지구성운동수행력 20 편 53 편 근력 or 무산소파워 2 편 23 편 혈중지질, 염증지표 8 편 32 편 연구성과요약 가시적인연구결과를보인연구분야 1) 속근섬유에서발견되는 ACTN3 ( 골격근유전자 ) 에관한연구 2) 알츠하이머질환에관련된분야 3) 세계적인운동선수들의운동수행력에관련된분야 ( 특히 ACE 유전자 ) 4) Myostatin 유전자및근육량변화에대한연구 Sports performance 중유산소지구성경기력 ( 마라톤, 중장거리달리기, 수영 ) 관련유전자 ACE 삽입 / 결손다형성 (ACE I/D 다형성 ) ACTN3 R577X 단일염기다형성 ACE 유전체 ACE 유전체 ACE(angio-tensine-converging enzyme) ACE I/D 다형성 인간의염색체 17q23에위치하는 ACE 유전자 16번인트론 (intron) 부위에 287bp Alu 염기서열이삽입또는결손으로 II, ID, DD 유전형이나타남 DD 유전형 II유전형보다 3배높은 ACE를가짐 ID 유전형 중간형 II 유전형 낮은 ACE 활성도 * 스포츠활동과스포츠분야에서가장많이연구된유전자 ACE DD 유전형 - 높은 ACE 활성에의해안지오텐신II의작용을증가시켜 심혈관계부담 ACE II 유전형 - 낮은안지오텐신 II의작용으로 혈관을쉽게이완시켜혈액순환을원활하게함 88

ACTN3 유전체 ACTN3 유전체와운동수행력 ACTN3 RR 유전형 ACTN3 유전자골격근의속근에근절의 Z-line을형성하는구조단백질인 α-actinin-3를발현하여속근섬유의특성인강하고빠른근수축을유도함 TypeⅡ muscle fiber 에서만발견된다.

3 ACTN3 유전체 ACTN3 유전체와운동수행력 ACTN3 RR 유전형 ACTN3 유전자골격근의속근에근절의 Z-line을형성하는구조단백질인 α-actinin-3를발현하여속근섬유의특성인강하고빠른근수축을유도함 TypeⅡ muscle fiber 에서만발견된다. α-actinine-3가속근에서발현 ACTN3 RX 유전자 α-actinin-3 발현이제한되어지근섬유에서주로발현되는 α-actinin-2가함께발현되어속근에근절의 Z-line을형성함 ACTN3 XX 유전자 - α-actinin-3 가전혀발현되지않아지근에서발현하는아형인 α-actinin-2가대체되어발현하여속근의근절에 Z-line을형성 ACTN3 유전체와운동수행력 골격근의속근섬유에서만기능적역할을하는 α- actinin-3의발현과억제그리고 α-actinin-2의대체된 발현혹은공동발현은속근섬유내근절의구조적기능적변이로인한근수축작용의차이를가져온다 α-actinin-2의대체성발현은속근에서지근이가지는특징으로유도하여지속적인근수축과유산소에너지대사에유리한형태로전환 A small number of excellent articles on exercise genomics issues were published in New reports on variants in ACTN3 and ACE increased the level of uncertainty regarding their true role in skeletal muscle metabolism and strength Positive effects of regular physical activity on body mass index as assessed by their FTO genotype The serum level of triglycerides / the risk of hypertriglycemia : SNP in the NOS3 Physical activity level SNPs at the RBPMS, YWHAQ, and CREB1 loci : strong predictors of changes in submaximal exercise heart rate 노화에따른구조적기능적변화 구조적변화 (Structural Change) 위축, 영양장애, 부종, 탄력성, 종양, 돌연변이 기능적변화 (Functional Consequences) 정밀도, 속도, 범위, 지구력, 협응력, 안정성, 근력 노화에따른주요생리기능적변화 심폐지구력감소 ( 5ml/kg/min per decade ) 체지방량증가 근력및제지방량감소 ( 25% ) 유연성감소 ( 7%/decade ) 골밀도감소 평형성감소 반응시간감소및운동수행시간지연 특별한감각기관의작용퇴화 ( 시각, 청각, 후각, 미각 ) 기억력감퇴, 수면장애, 우울증 89

4 대한임상건강증진학회 2014 추계학술대회 Skeletal muscle gene expression profiles in old and young women 노화에따른운동에대한근유전자표현형의변화 (1) Gene expression profiling may provide leads for investigations of the molecular basis of functional declines associated with aging. The most highly overexpressed genes(>3-fold) in older muscle were p21(cyclin-dependent kinase inhibitor 1A), which might reflect increased DNA damage, perinatal myosin heavy chain, which might reflect increased muscle fiber regeneration, and tomoregulin. More than 40 genes encoding proteins that bind to pre-m RNA or m RNAs were expressed at higher levels in older muscle. More than 100 genes involved in energy metabolism were expressed at lower levels in older muscle The gene expression profile of skeletal muscle from healthy older(62-75 years old) : stress, damage response ( ), DNA repair/cell cycle check point proteins ( ) The expression of the inflammatory response gene(il-1ß) : lack of response to resistance EX (older adults) 노화에따른운동에대한근유전자표현형의변화 (2) The adaptation of muscle to EX in the processes of angiogenesis & cell proliferation : older subjects = younger subjects ERG-1 ( growth response transcription factor) : Younger subjects ( ), older subjects ( ) Proteolytic Gene Expression & Muscle Atropy Higher m-rna levels of MuRF-1, FOXO3A in old women compared to young women ( At Rest) Responses to an acute resistance exercise(hypertrophic stimulus) 1) atrogin-1 : age effect ( OW : 2.5- fold) 2) MuRF-1 : no age effect ( YW : 3.6, OW : 2.6- fold) The regulation of ubiquitin proteasome-related genes involved with muscle atrophy are altered in very old women(> 80 years) Expression of notch signaling genes & Aging Notch signaling : essential for myogenesis and the regenerative potential of skeletal muscle Significantly lower expressions of Notch 1, Jagged 1, Numb, Delta-like 1 in older man(60-75 years old) The differences in Notch expression between the age groups were no longer evident following training. Reference Bouchard C, Sarzynski MA, Rice TK, et al. Genomic predictors of the maximal O(2) uptake response to standardized exercise training programs. J Appl Physiol. 2011;110(5): Dhamrait SS, Williams AG, Day SH, et al. Variation in the uncoupling protein 2 and 3 genes and human performance. J Appl Physiol. 2012;112(7): Eynon N, Ruiz JR, Femia P, et al. The ACTN3 R577X polymorphism across three groups of elite male European athletes. PLoS One. 2012;7(8):e Folland JP, Mc Cauley TM, Phypers C, Hanson B, Mastana SS. The relationship of testosterone and AR CAG repeat genotype with knee extensor muscle function of young and older men. Exp Gerontol. 2012;47(6): Higashibata T, Hamajima N, Naito M, et al. enos genotype modifies the effect of leisure-time physical activity on serum triglyceride levels in a Japanese population. Lipids Health Dis. 2012; 11(1):150. Kacerovsky-Bielesz G, Kacerovsky M, Chmelik M, et al. A single nucleotide polymorphism associates with the response of muscle ATP synthesis to long-term exercise training in relatives of type 2 diabetic humans. Diabetes Care. 2012;35(2): MacArthur DG, Seto JT, Chan S, et al. An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance. Hum Mol Genet. 2008;17(8): MacArthur DG, Seto JT, Raftery JM, et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet. 2007;39(10): Qi Q, Li Y, Chomistek AK, et al. Television watching, leisure time physical activity, and the genetic predisposition in relation to body mass index in women and men. Circulation. 2012;126(15):

Reference Rice TK, Sarzynski MA, Sung YJ, et al. Fine mapping of a QTLs on chromosome 13 for submaximal exercise capacity training response: the HERITAGE Family Study. Eur J Appl Physiol.

5 Reference Rice TK, Sarzynski MA, Sung YJ, et al. Fine mapping of a QTLs on chromosome 13 for submaximal exercise capacity training response: the HERITAGE Family Study. Eur J Appl Physiol. 2012; 112(8): U.S. Department of Health and Human Services Physical Activity Guidelines for Americans. Washington, DC: U.S. Department of Health and Human Services; Vincent B, Windelinckx A, Van Proeyen K, et al. Alpha-actinin-3 deficiency does not significantly alter oxidative enzyme activity in fast human muscle fibres. Acta Physiol (Oxf). 2012;204(4): Perusse Louis, Rankinen T, hagberg J. M, Loos R. J, Roth S. M, Sarzynski M. A, et al. Advances in Exercise, Fitness, and Performance Genomics in Medicine & Science in Sports & Exercise. 2013;45(5): Bouchard C. Overcoming Barriers to Progress in Exercise Genomics. Exerc Sport Sci Rev. 2011;39(4): Ash G. I, Eicher j. D, psescatello L. S. The Promises and Challenges of the Use of Genomics in the Prescription of Exercise for Hypertension: The 2013 Update. Current Hypertension Reviews, 2013;9(2):

한국성인에서초기황반변성질환과 연관된위험요인연구

한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 - - i - - i - - ii - - iii - - iv - χ - v - - vi - - 1 - - 2 - - 3 - - 4 - 그림 1. 연구대상자선정도표 - 5 - - 6 - - 7 - - 8 - 그림 2. 연구의틀 χ - 9 - - 10 - - 11 -