weissman-shomer 1975 mech ageing dev - chick embryo fib rob lasts senscence in

8/3/2019 Weissman-Shomer 1975 Mech Ageing Dev - Chick Embryo Fib Rob Lasts Senscence In

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M echanism s o f Ageing and D e velopment , 4 (1975) 159-166 159 Elsevier Sequoia S.A., Lausanne - Printed in The Netherlands

C H I C K E M B R Y O F I B R O B L A S T S S E N E S C E N C E I N V I T R O : P A T T E R N O FC E L L D I V I S I O N A N D L I F E S P A N A S A F U N C T I O N O F C E L L D E N S I T Y

PN1 NA WEISSMAN-SHOMER an d MIC HA EL FRYDepartment o f Clinical Biochemistry, Technion, The Aba K houshy School o f Medieine in Hai]a, H aifa(Israel)(Received August 6, 1974; in revised form January 27, 1975)

S U M M A R YT h e p a t t e r n o f c e ll d i v is i o n , a g e i n g a n d d e a t h o f c u l t u r e d c h i c k e m b r y o f i b r o -

b l a s t s i n o c u l a t e d a t a w i d e r a n g e o f c e l l d e n s i t i e s is d e s c r i b e d . C e l l p o p u l a t i o n s s e e d e da t d en s i t i e s o f 2.1 1 0 z t o 3 .1 1 04 ce l l s p e r c m 2 d o u b l e b e tw ee n 3 9 an d 1 7 t im esr e s p e c t i v e l y w h i l e t h e i r li f e s p a n a t a l l d e n s i t i e s r e m a i n s 5 7 : ~ 3 d a y s . T h u s , u n d e r t h ee x p e r i m e n t a l c o n d i t i o n s e m p l o y e d , t h e li fe s p a n o f c u l t u r e d e m b r y o n i c c h i c k c el ls i s af u n c t i o n o f c a l e n d a r r a t h e r t h a n m i t o t i c t i m e . W e a l s o f in d th a t t h e d u r a t i o n o f p h a s eI I I a n d t h e g e n e r a t i o n t i m e o f th e c e ll s d u r i n g t h i s p e r i o d a r e p r o p o r t i o n a l t o t h ed e n s i t y o f t h e c u l tu r e . M o r e o v e r , t h e d i v i s i o n r a t e o f c el ls i n o c u l a t e d a t l o w d e n s i t ie s( 4 . 2 - 3 1 . 0 1 0 z c e ll s p e r c m 2 ) r e m a i n s c o n s t a n t t h r o u g h o u t t h e i r e n t i r e l i f e ti m e . I t i ss u g g e s t e d t h a t t h e d e c l in e i n t h e p r o l i f e r a t i v e c a p a c i t y o f c h i c k c e ll s a g e in g i n v i t ro is af u n c t i o n o f b o t h t h e i r d e n s i t y a n d t h e i r a g e .

I N T R O D U C T I O NC h i c k e m b r y o f i b r o b l a s t s l - a , a s w e l l as h u m a n d i p l o i d f i b r o b l a s t s 4 -8 , e m b r y o -

n i c h e a r t c e ll s o f t h e m a r s u p i a l P o t o r o u s t r i d a c ty l i s 9 a n d c e l l s f r o m G a l a p a g o s t o r -t o i s e 10 h a v e a l i m i t e d l i fe s p a n i n v i t ro . T h e p a t t e r n o f c e ll u la r g r o w t h a n d s e n es c e nc eo f n o r m a l c u l t u r e d c e l ls c o n s i s ts o f a n i n i t ia t i o n p e r i o d ( " p h a s e I " ) f o l l o w e d b y ap e r i o d o f r a p i d m u l t i p l i c a t i o n o f t h e ce ll s ( " p h a s e I I ) " w h i c h e v o l v e s i n t o a p e r i o d o fg r a d u a l d e c li n e in t h e p r o l i f e r a t i v e c a p a c i t y o f t h e c e ll s ( " p h a s e I l l ) " u l t i m a t e l y l e a d -i n g to d e a t h o f t h e c ul tu r e . A l t h o u g h t h e m e c h a n i s m o f t hi s p h e n o m e n o n h a s n o t y e tb e e n e l u c i d a t e d i t m a y b e r e g a r d e d a s a n i n v i t ro m o d e l s y s t e m f o r c e l l u l a r a g e i n g 2 , 3,5 , 1 t a n d s e v e r a l t h e o r i e s h a v e b e e n o f f e r e d i n t h e r e c e n t y e a r s t o e x p l a i n t h e l i m i t e dsu rv iva l o f cu l tu re d ce l l st ra ins2,12,13A4.

T h e p a t t e r n o f g r o w t h o f c u lt u r e d f i b ro b l a s ts p o s e s s e v e r al u n r e so l v e d p r o -b l e m s . O n e q u e s t i o n i s t h e i n t e r p r e t a t i o n o f p h a s e I I I a s r e l a t e d t o c e ll d iv i s io n .C e s s a t i o n o f c e ll u la r p r o l i fe r a t i o n d u r i n g p h a s e I I I c o u l d r e s u lt f r o m a u n i f o r m i n-c r e a s e i n t h e g e n e r a t i o n t i m e o f a ll c el ls , a l te r n a t i v e l y i t c o u l d b e d u e t o t h e a p p e a r -a n c e o f a n i n c r e a s i n g p o p u l a t i o n o f n o n d i v i d i n g c e ll s, o r c o u l d b e d u e t o b o t h . T h e


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weissman-shomer 1975 mech ageing dev - chick embryo fib rob lasts senscence in

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