Functionally significant insulin-like growth factor I receptor mutations in centenarians
Language: 
English
Abstract: 

Rather than being a passive, haphazard process of wear and tear, lifespan can be modulated actively by components of the insulin/insulin-like growth factor I (IGFI) pathway in laboratory animals. Complete or partial loss-of-function mutations in genes encoding components of the insulin/IGFI pathway result in extension of life span in yeasts, worms, flies, and mice. This remarkable conservation throughout evolution suggests that altered signaling in this pathway may also influence human lifespan. On the other hand, evolutionary tradeoffs predict that the laboratory findings may not be relevant to human populations, because of the high fitness cost during early life. Here, we studied the biochemical, phenotypic, and genetic variations in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls and demonstrated a gender-specific increase in serum IGFI associated with a smaller stature in female offspring of centenarians. Sequence analysis of the IGF1 and IGF1 receptor (IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes. Thus, genetic alterations in the human IGF1R that result in altered IGF signaling pathway confer an increase in susceptibility to human longevity, suggesting a role of this pathway in modulation of human lifespan.

Author(s): 
Suh, Yousin
Atzmon, Gil
Cho, Mi-Ook
Hwang, David
Liu, Bingrong
Leahy, Daniel J.
Barzilai, Nir
Cohen, Pinchas
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
3/4/2008
Publication Year: 
2008
Pages: 
3438-3442
Volume: 
105
Issue: 
9
ISSN: 
1091-6490
DOI: 
10.1073/pnas.0705467105
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 18316725 PMCID: PMC2265137

Turabian/Chicago Citation

Yousin Suh, Gil Atzmon, Mi-Ook Cho, David Hwang, Bingrong Liu, Daniel J. Leahy, Nir Barzilai and Pinchas Cohen. 3/4/2008. "Functionally significant insulin-like growth factor I receptor mutations in centenarians." Proceedings of the National Academy of Sciences of the United States of America 105: 9: 3438-3442. 10.1073/pnas.0705467105.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.0705467105 | issn = 1091-6490 | volume = 105 | pages = 3438-3442 | last = Suh | first = Yousin | coauthors = Atzmon, Gil, Cho, Mi-Ook, Hwang, David, Liu, Bingrong, Leahy, Daniel J., Barzilai, Nir, Cohen, Pinchas | title = Functionally significant insulin-like growth factor I receptor mutations in centenarians | journal = Proceedings of the National Academy of Sciences of the United States of America | date = 3/4/2008 | pmid = | pmc = }} </ref>