THE RATE OF TELOMERE SEQUENCE LOSS IN HUMAN-LEUKOCYTES VARIES WITH AGE

A gradual loss of telomeric repeat sequences with aging previously has been noted in normal adult tissues, and this process has been implica ted in cell senescence. No data exist that address the rate of telomer e shortening in normal human cells within families or early in life. T o address these questions, we measured telomere lengths in peripheral blood leukocytes (PBLs) from 75 members of 12 families and in a group of unrelated healthy children who were 5-48 months old. Here we report the surprising observation that rates of telomere attrition vary mark edly at different ages, Telomeric repeats are lost rapidly (at a rate of >1 kilobase per year) from the PBLs of young children, followed by an apparent plateau between age 4 and young adulthood, and by gradual attrition later in life. These data suggest that the loss of telomeric repeats in hematopoietic cells is a dynamic process that is different ially regulated in young children and adults. Our results have implica tions for current models of how telomeric sequences are lost in normal somatic cells and suggest that PBLs are an excellent tissue to invest igate how this process is controlled.