Open AccessLongevity is not influenced by prenatal programming of body size
Author(s) -
Conover Cheryl A.,
Bale Laurie K.,
Grell Jacquelyn A.,
Mader Jessica R.,
Mason Megan A.
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00589.x
Subject(s) - longevity , biology , fetus , imprinting (psychology) , endocrinology , insulin like growth factor , growth factor , pregnancy , medicine , andrology , physiology , genetics , receptor , gene
Summary Insulin‐like growth factor (IGF) signaling is essential for achieving optimal body size during fetal development, whereas, in the adult, IGFs are associated with aging and age‐related diseases. However, it is unclear as to what extent lifespan is influenced by events that occur during development. Here, we provide direct evidence that the exceptional longevity of mice with altered IGF signaling is not linked to prenatal programming of body size. Mice null for pregnancy‐associated plasma protein‐A (PAPP‐A), an IGF‐binding protein proteinase that increases local IGF bioavailability, are 60–70% the size of their wild‐type littermates at birth and have extended median and maximum lifespan of 30–40%. In this study, PAPP‐A −/− mice whose body size was normalized during fetal development through disruption of IgfII imprinting did not lose their longevity advantage. Adult‐specific moderation of IGF signaling through PAPP‐A inhibition may present a unique opportunity to improve lifespan without affecting important aspects of early life physiology.