Extension of cell life-span and telomere length in animals cloned from senescent somatic cells.
The potential of cloning depends in part on whether the procedure can reverse cellular aging and restore somatic cells to a phenotypically youthful state. Here, we report the birth of six healthy cloned calves derived from populations of senescent donor somatic cells. Nuclear transfer extended the replicative life-span of senescent cells (zero to four population doublings remaining) to greater than 90 population doublings. Early population doubling level complementary DNA-1 (EPC-1, an age-dependent gene) expression in cells from the cloned animals was 3.5- to 5-fold higher than that in cells from age-matched (5 to 10 months old) controls. Southern blot and flow cytometric analyses indicated that the telomeres were also extended beyond those of newborn (<2 weeks old) and age-matched control animals. The ability to regenerate animals and cells may have important implications for medicine and the study of mammalian aging.
Lanza
R P
RP
Advanced Cell Technology, One Innovation Drive, Worcester, MA 01605, USA. rlanza@advancedcell.com
Cibelli
J B
JB
Blackwell
C
C
Cristofalo
V J
VJ
Francis
M K
MK
Baerlocher
G M
GM
Mak
J
J
Schertzer
M
M
Chavez
E A
EA
Sawyer
N
N
Lansdorp
P M
PM
West
M D
MD
D000818:Animals; D015139:Blotting, Southern; D002417:Cattle / Q000235:genetics*; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence; D002999:Clone Cells; D019976:Cloning, Organism; D018076:DNA, Complementary; D004624:Embryo Transfer; D005136:Eye Proteins; D005260:Female; D005347:Fibroblasts; D005434:Flow Cytometry; D017404:In Situ Hybridization, Fluorescence; D008136:Longevity; D016555:Matched-Pair Analysis; D009414:Nerve Growth Factors; D053652:Nuclear Transfer Techniques; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics; D016615:Telomere / Q000648:ultrastructure*; D000099174:Pigment Epithelium-Derived Factor
D018076:DNA, Complementary; D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor