TY - JOUR
T1 - Age-dependent skewing of X chromosome inactivation appears delayed in centenarians' offspring. Is there a role for allelic imbalance in Healthy Aging and Longevity?
AU - Gentilini, Davide
AU - Castaldi, Davide
AU - Mari, Daniela
AU - Monti, Daniela
AU - Franceschi, Claudio
AU - di Blasio, Anna Maria
AU - Vitale, Giovanni
PY - 2012/4
Y1 - 2012/4
N2 - Recently, it has been proposed that age-related X chromosome inactivation (XCI) skewing can clinically result in late-onset X-linked disorders. This observation leads to hypothesize that age-related skewed XCI might also influence lifespan in women. To investigate this issue, we employed a new experimental model of longevity and healthy aging including 55 female centenarians, 40 of their offspring, 33 age-matched offspring of both non-long-lived parents and 41 young women. Peripheral blood DNA from 169 females was screened for heterozygosity at the HUMARA locus. We confirmed that skewing of XCI is an age-dependent phenomenon. However, skewed XCI was significantly less severe and frequent in centenarians' offspring [degree of skewing (DS)=0.16±0.02] compared to age-matched offspring of both non-long-lived parents (DS= 0.24±0.02) (P
AB - Recently, it has been proposed that age-related X chromosome inactivation (XCI) skewing can clinically result in late-onset X-linked disorders. This observation leads to hypothesize that age-related skewed XCI might also influence lifespan in women. To investigate this issue, we employed a new experimental model of longevity and healthy aging including 55 female centenarians, 40 of their offspring, 33 age-matched offspring of both non-long-lived parents and 41 young women. Peripheral blood DNA from 169 females was screened for heterozygosity at the HUMARA locus. We confirmed that skewing of XCI is an age-dependent phenomenon. However, skewed XCI was significantly less severe and frequent in centenarians' offspring [degree of skewing (DS)=0.16±0.02] compared to age-matched offspring of both non-long-lived parents (DS= 0.24±0.02) (P
KW - Centenarians
KW - Genetics
KW - Life span
KW - Longevity
KW - Longevity regulation
KW - Molecular biology of aging
UR - http://www.scopus.com/inward/record.url?scp=84858336995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858336995&partnerID=8YFLogxK
U2 - 10.1111/j.1474-9726.2012.00790.x
DO - 10.1111/j.1474-9726.2012.00790.x
M3 - Article
C2 - 22292741
AN - SCOPUS:84858336995
VL - 11
SP - 277
EP - 283
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 2
ER -