Women with delayed menopause and those who give birth to children later in life show less cardiovascular disease and live longer than other women. Women with constitutively long leukocyte telomere length (LTL) have delayed menopause, show less cardiovascular disease and also live longer than other women. The central hypothesis of this proposal is a logical extension of these findings. It posits that women who bear children later in life without the use of assisted reproductive technologies might have a constitutively long LTL. A corollary of this hypothesis is that offspring of these women might have a long LTL as well, given that LTL is highly heritable. Moreover, children born to older women are typically conceived by older men. As the offspring's LTL is positively associated with paternal age at the time of conception of the offspring, LTL of offspring conceived by older women might be constitutively longer than average due to the joint effects of heritability of a longer LTL from the mothers and being conceived by older fathers. This central hypothesis and its corollary will be tested in the Norwegian Mother and Child Cohort Study (MoBa) ? a pregnancy and birth cohort with a Biobank of leukocyte DNA samples and a comprehensive dataset.
The aims of the study are: 1) measure LTL in 1700 mothers who gave birth at ages 18 years or older, including 1000 mothers who gave birth at the age 35 years and older; 2) measure LTL in 300 mothers who gave birth at the age of 35 years and older with the aid of in-vitro fertilization; 3) measure LTL in the 2,000 fathers (the sexual partners) of the mothers in aims 1 and 2); and 4) measure LTL in newborns of these parentsand perform an instrumental variable analysis, further exploring the relationship between maternal LTL and fecundity. Learning about LTL using the mother-father-newborn study design will broaden our understanding of the familial framework of female fecundity and of having long (and short) LTL. This understanding is vital for public health, given that LTL is associated with a host of aging-related disorders and with longevity in contemporary humans.
This study will examine the association of leukocyte telomere length with female fecundity. The following hypotheses will be tested: a) women who give birth at an older age have constitutively long telomeres; b) women who give birth with the assistance of in vitro fertilization have constitutively short telomeres; c) offspring of women who give birth at an older age inherit long telomeres, while offspring of mothers who resorted to in vitro fertilization inherit short telomeres. These hypotheses will be tested in 2,000 newborn-mother-father trios.
|Khan, Sadiya S; Shah, Sanjiv J; Klyachko, Ekaterina et al. (2017) A null mutation in SERPINE1 protects against biological aging in humans. Sci Adv 3:eaao1617|