The insulin-like growth factor (IGF) system is highly conserved across species and plays a critical role in all phases of the mammalian life cycle, from fetal development through childhood / pubertal growth and adulthood. Insulin-like growth factor-1 (IGF-I), an important peptide hormone of the IGF system, is involved in regulation cell cycle - promoting cell proliferation and somatic growth while inhibiting apoptosis - in tissues throughout the body. In humans, the role of the IGF system in aging and age-related diseases is still poorly understood, though this field of research has raised hopes for new drugs that slow the aging process by modulating IGF pathways. The present study will assess the association of circulating levels of IGF-I, IGF-I, and IGF binding proteins (IGFBP-1, IGFBP-2, IGFBP-3) with functional limitation, disability, performance-based tests of physical function, brain morphologic changes, and survival/longevity among older adults. The study will use specimens and data from the Cardiovascular Health Study (CHS) cohort - a large multi-center NIH-funded cohort of n=5,888 community-dwelling men and women 65 years or older, with detailed longitudinal data capturing age-related outcomes. Follow-up in CHS is now over 15 years, which will allow us to go beyond any prior studies by defining within-individual trajectories of IGF-I and IGFBP levels from repeated blood samples, and relating these measurements to age-related outcomes. Further studies will identify genetic determinants of IGF-I and IGFBPs using a whole-genome approach, with replication in the Framingham and Rotterdam cohorts. 11/3/2008 1 K: PI_Administration Kaplan Nov 5 2008 revision Abstract _ Oct08.doc Created on 10/31/2008 10:45:00 AM

Public Health Relevance

The insulin-like growth factor (IGF) system appears to play a major role in the aging process. However, in humans, the role of the IGF system in aging and age-related diseases is still poorly understood. This project will assess the relationship of the IGF system with disability, changes in brain structure, and longevity among 65+ year old men and women, with the long-term goal of informing the development of new drugs that slow the aging process by modulating IGF pathways. 11/3/2008 1 K: PI_Administration Kaplan Nov 5 2008 revision Narrative.doc Created on 6/1/2007 4:07:00 PM

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Joseph, Lyndon
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Albert Einstein College of Medicine
Public Health & Prev Medicine
Schools of Medicine
United States
Zip Code
Beasley, Jeannette M; Wedick, Nicole M; Rajpathak, Swapnil N et al. (2014) Circulating IGF-axis protein levels and their relation with levels of plasma adipocytokines and macronutrient consumption in women. Growth Horm IGF Res 24:142-9
Wang, Tao; Zhou, Baiyu; Guo, Tingwei et al. (2014) A robust method for genome-wide association meta-analysis with the application to circulating insulin-like growth factor I concentrations. Genet Epidemiol 38:162-71
Rosenberg, Michael A; Kaplan, Robert C; Siscovick, David S et al. (2014) Genetic variants related to height and risk of atrial fibrillation: the cardiovascular health study. Am J Epidemiol 180:215-22
Kim, Ryung S; Kaplan, Robert C (2014) Analysis of secondary outcomes in nested case-control study designs. Stat Med 33:4215-26
Sanders, Jason L; Ding, Victoria; Arnold, Alice M et al. (2014) Do changes in circulating biomarkers track with each other and with functional changes in older adults? J Gerontol A Biol Sci Med Sci 69:174-81
Broer, L; Demerath, E W; Garcia, M E et al. (2013) Association of heat shock proteins with all-cause mortality. Age (Dordr) 35:1367-76
Ochs-Balcom, Heather M; Preus, Leah; Wactawski-Wende, Jean et al. (2013) Association of DXA-derived bone mineral density and fat mass with African ancestry. J Clin Endocrinol Metab 98:E713-7
Banerjee, Dipanjan; Biggs, Mary L; Mercer, Laina et al. (2013) Insulin resistance and risk of incident heart failure: Cardiovascular Health Study. Circ Heart Fail 6:364-70
Kaplan, Robert C; Buzkova, Petra; Cappola, Anne R et al. (2012) Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study. J Clin Endocrinol Metab 97:1970-6
Kaplan, Robert C; Petersen, Ann-Kristin; Chen, Ming-Huei et al. (2011) A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3. Hum Mol Genet 20:1241-51

Showing the most recent 10 out of 15 publications