title: Extension of cell life-span and telomere length in animals cloned from senescent somatic cells.
abstract: 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.
authors.affiliation: Advanced Cell Technology, One Innovation Drive, Worcester, MA 01605, USA. rlanza@advancedcell.com
authors.forename: R P
authors.initials: RP
authors.lastname: Lanza
authors.forename: J B
authors.initials: JB
authors.lastname: Cibelli
authors.forename: C
authors.initials: C
authors.lastname: Blackwell
authors.forename: V J
authors.initials: VJ
authors.lastname: Cristofalo
authors.forename: M K
authors.initials: MK
authors.lastname: Francis
authors.forename: G M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: J
authors.initials: J
authors.lastname: Mak
authors.forename: M
authors.initials: M
authors.lastname: Schertzer
authors.forename: E A
authors.initials: EA
authors.lastname: Chavez
authors.forename: N
authors.initials: N
authors.lastname: Sawyer
authors.forename: P M
authors.initials: PM
authors.lastname: Lansdorp
authors.forename: M D
authors.initials: MD
authors.lastname: West
mesh_terms: 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
chemical_list: D018076:DNA, Complementary; D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor