Georgian Scientists/ . 6 N 3, 2024 228 Georgian Scientists Vol. 6 Issue 4, 2024 https://doi.org/10.52340/gs.2024.06.04.21 1 1 , , jtkemaladze@longevity.ge, https://orcid.org/0000-0001-8651-7243 . , , . , . , . , , , , . : ; ; ESC; ASC; ; ; ; ; . (ESCs), ( , , ) , , . ESC- , , , , . , . (ASCs) , Georgian Scientists/ . 6 N 3, 2024 229 . ASC , , , . 1 (Erceg et al., 2023) ASC- ; - . ASC . , , , . . ASC , Georgian Scientists/ . 6 N 3, 2024 230 . , , , , , . , , . ( ). Hayflick- . , . ASC . ASC . , , , . , ( , ) . , ASC . , , (ROS) , . , . , , , ( ). . , . . , . , . Georgian Scientists/ . 6 N 3, 2024 231 Thomson- Gearhart- ESC- (hESCs) . in vitro. , , ESCs (pESCs) . (SSEA)-1, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, . , . , . , . , , ) , . , TRA-1-60 TRA-1-81 , , ESCs TRA-1-60 TRA. -1-81 . , Oct-4 ESCs (mESCs) , (LIF). hESC- . , , ? Brüstle et al hESC- in vitro , , . ES , . : 1) (FGF2), 2) FGF2 (EGF) 3) FGF2 (PDGF). , , . , , , Georgian Scientists/ . 6 N 3, 2024 232 . , , , . , , hESC- in vitro . . Rb-E2F , - (Cdks) Cdk INK4a/ARF . . , . , ESC- , mESC mESC- , (mEPLC). mESC- . 4.5- 6.0 dpc- ( ), 10 . 6.5- 7.0 dpc- , 4.4 . , mESC- mEPLC- G1 G2 ( 50-60%) S . , Rb/p105, , E2F , (R ). Rb/p105- CDK . Ras/Raf/ (MAPK) D - CDK4/6 , , , Rb/p105 . R E/CDK2 Rb/p105 E2F , S . , , , , , . ESC , , R G1 - S . Stead , mESC- , Georgian Scientists/ . 6 N 3, 2024 233 mEPLC- CDK2, A E . , CDK2 , . CDC2 - B, G2 - M , CDK , E2F . Rb/p105- . Rb/p105- mESC- mEPLC- . E CDK2- , , Rb/p105 , R ESC . MAPK , , . , mESCs D CDK4 . Rb/p105 , mESC- . G1- mESC- , MAPK , . , mESC- , hESC- G1 , hESC- . , ESC- mESC- E- , Rb/p105- MAPK- . , , , hESC- . , ESC CDK , Rb/p105 E2F , G1 , . . , , , . . , , , . Georgian Scientists/ . 6 N 3, 2024 234 , . , , , , , , . ASC- (HSCs MSCs). HSCs , . , HSC , . , , , . HSC- : HSCs (LTR-HSCs), HSCs (STR-HSCs). , . , HSC- , LTR-HSC- . MSC , HSC- , , , , , , . MSC -MSC : MAPC, hBMSC, USSC, FSSC, AFS, MIAMI , hFLMPC MASC. , - MSC- , , , . , , . (HSCs MSCs) , in vitro. , , . in vitro , . , . , , Georgian Scientists/ . 6 N 3, 2024 235 . , ESC- , . , , , . Rossi et al. , 34000 907, HSC- , , , . , , HSC- . , HSC- . , ES , in vivo, . , , CDK , CDK- , . , CDK . CDK ASC- HSC- . , , ASC . ESC , , G1 R , . , , , . , , , . , . . p16 Ink4a , , Rb/p105 . Georgian Scientists/ . 6 N 3, 2024 236 . p16Ink4a- , p16Ink4a . INK4a /ARF p16Ink4a p19Arf , Rb p53 . INK4a /ARF , - . p16 Ink4a D1 - CDK4, D2 - CDK4 D3 - CDK6 . D CDK Rb/p105, Rb/p105 E2F-1, 2, 3, 4- , . E2F G1 . p19Arf p53- , p53- . p19Arf- . p16Ink4a- , p19Arf , , . , . , Bmi-1 p16Ink4a p19Arf- INK4a/ARF . Bmi-1 -/- p16Ink4a- . Park- , Bmi-1 HSC . Bmi-1 -/- , P16Ink4a p19Arf HSC- , p53- . Bmi-1 -/- P16Ink4a . Bmi-1 Polycomb (PcG) RING , PcG PRC1. PRC1 , . Pcgf, Ring1, Phc Cbx . PRC2 , . , PRC1 PRC2 , . PRC2- ESC- , . , PRC1 PRC2 Georgian Scientists/ . 6 N 3, 2024 237 , . , PcG INK4a/ARF . Jacobs , Mel-18 Cbx7 INK4a/ARF . Cbx7 PcG , PRC1- , , . , Cbx7 INK4a/ARF p16Ink4a /Rb p19Arf /p53 . ASC , PcG . Nishino Hmga2- . Hmga2 , . , let-7b- . Let-7b- Hmga2- , Hmga2 . p16 Ink4a- p19 Arf- . , Hmga2- . , ASC , INK4a/ARF , , ASC- , MSC- in vitro . Rb . , , , p107 Rb/p105. , Rb2/p130 MSC- . , Rb2/p130 MSC . , Rb2/p130- HDAC1- , E2F- , A, G 0 , , Rb2/p130 . , PcG . , INK4a/ARF , , . , , Hmga2, let-7b Rb2/p130, . , Georgian Scientists/ . 6 N 3, 2024 238 . , , . , . (Tkemaladze et al., 2001-2024) , , , ( 2). 2 . G1 , de novo '1' '2'. - , . de novo , - Georgian Scientists/ . 6 N 3, 2024 239 1 , 2 . . , G1 . ( ) , . . . ( 1) , - . , . . . - , , . . , , . ASC- . . / . - , . . , / - , . , ASC- . , . ASC- , . , , . Georgian Scientists/ . 6 N 3, 2024 240 1. Chichinadze, K., Lazarashvili, A., & Tkemaladze, J. (2013). RNA in centrosomes: structure and possible functions. Protoplasma, 250(1), 397-405. 2. 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Programming and Implementation of Age-Related Changes. In Senescence. IntechOpen. Georgian Scientists/ . 6 N 3, 2024 242 30. Tkemaladze, J., & Chichinadze, K. (2010). Centriole, differentiation, and senescence. Rejuvenation research, 13(2-3), 339-342. 31. Tkemaladze, J. V., & Chichinadze, K. N. (2005). Centriolar mechanisms of differentiation and replicative aging of higher animal cells. Biochemistry (Moscow), 70, 1288-1303. 32. Tkemaladze, J., & Chichinadze, K. (2005). Potential role of centrioles in determining the morphogenetic status of animal somatic cells. Cell biology international, 29(5), 370-374. 33. , . ., , . ., , . ., , . ., , . ., & , . . (2017). . (MLSD’2016)» :• , , ., 284. 34. , ., , ., & , . (2001). . . 004.89. . 004.89. The rate of stem cell division decreases with age Jaba Tkemaladze1 1Research Director, Longevity Clinic Georgia Inc. jtkemaladze@longevity.ge Abstract Intracellular repair and protection mechanisms determine the lifespan of an individual cell. Somatic stem cells determine the lifespan of all tissues and thus play an important role in the aging process of the body. Stem cells possess extensive self-renewal properties, but there is considerable evidence of their decline and erosion over time. The reason why the rate of division of stem cells decreases after each division is not yet determined. Interestingly, stem cells during asymmetric division selectively accumulate, on the one hand, newer molecules and structures, and on the other hand, older centrioles. Keywords: stem cells; differentiation; ESC; ASC; apoptosis; ontogenesis; self recovery; senescence; aging