We will investigate factors involved in the rate of metabolic and cardiovascular aging in men and women in the Fels Longitudinal Study (FLS). Although it is possible to age in good health, in the U.S. population progressive weight gain (Yanovski et al 2000) and an increasing prevalence of the metabolic syndrome are common attributes of aging. The prevalence of adults in the FLS with BMI >25kg/m2 increases from 30% in the fourth decade of life to 70% in the sixth decade, and the prevalence of the metabolic syndrome increase from 21% to 38% in men and from 14% to 34% in women the same age groups. Tempo of growth and development: We plan to ascertain the influence of a prolonged juvenile state, i.e., a retarded tempo of physiological development, on delaying the onset of the metabolic syndrome, cardiovascular disease (CVD), and type 2 diabetes mellitus (T2DM) later in life. To achieve this goal, we propose to link risk factors for these common but unhealthy features of aging to childhood tempo of physiological development. The tempo of physiological development will be determined in each subject by documenting his or her age at the time of the adiposity rebound;the onset of the pubertal growth spurt; the peak height velocity; menarche; and his or her bone age at each of these milestones. The temporal range of these milestones varies from 5 years for the adiposity rebound to nearly 8 years for menarche, and bone age may lag behind or jump ahead of chronological age by as much as 4.5 years in either direction. We plan to accomplish our objectives using long-term serial data collected from birth over periods as long as 75 years in 361 adult males and 354 adult females in the FLS. Juvenile protective factors: We also propose to examine levels of biomarkers measured in childhood and adolescence that are associated with a delayed onset of the metabolic syndrome, CVD, and T2DM. Such delays may be caused by the persistence of juvenile levels of protective factors into adulthood, or else by the persistence into adulthood of effects initiated by such factors in childhood. The biomarkers we will study include body composition, lipid profiles, adipokines, inflammatory markers, insulin resistance, insulin-like growth factor-1 (IGF-1), and adrenal androgens. We plan to identify which of these biomarkers measured during childhood and adolescence act to delay the onset of the metabolic syndrome, CVD, and T2DM and could be considered as juvenile protective factors. The proposed analysis of serial data collected over decades should reveal the natural history of the onset of the metabolic syndrome, CVD, and T2DM in relation to the tempo of growth and development during the first two decades of life and in relation to levels of biomarkers during childhood and adolescence that could be considered to be juvenile protective factors. We are examining features of childhood that prevent or delay the onset of unhealthy aspects of aging.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD060913-02
Application #
7778889
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (M2))
Program Officer
Winer, Karen
Project Start
2009-03-01
Project End
2012-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
2
Fiscal Year
2010
Total Cost
$287,482
Indirect Cost
Name
Virginia Commonwealth University
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
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Chen, Wenan; Ren, Chunfeng; Qin, Huaizhen et al. (2015) A Generalized Sequential Bonferroni Procedure for GWAS in Admixed Populations Incorporating Admixture Mapping Information into Association Tests. Hum Hered 79:80-92
Kang, Le; Chen, Weijie; Petrick, Nicholas A et al. (2015) Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach. Stat Med 34:685-703
Sun, Shumei S; Sima, Adam P; Himes, John H (2014) Retarded tempo of physiological development in childhood delays the onset of the metabolic syndrome in adulthood. Ann Nutr Metab 65:175-83
Sabo, Roy T; Ren, Chungfeng; Sun, Shumei S (2012) Comparing Height-Adjusted Waist Circumference Indices: The Fels Longitudinal Study. Open J Endocr Metab Dis 2:40-48
Sun, S S; Sabo, Roy; Arslanian, S et al. (2012) Age variation and sexual dimorphism in the sixteen diagnostic clusters of risk factors for the metabolic syndrome. Z Gesundh Wiss 20:487-497
Frank, L Matthew; Shinnar, Shlomo; Hesdorffer, Dale C et al. (2012) Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study. J Pediatr 161:1169-71
Wan, Wen; Deng, Xiaoyan; Archer, Kellie J et al. (2012) Pubertal pathways and the relationship to anthropometric changes in childhood: The Fels longitudinal study. Open J Pediatr 2:
Sun, Shumei S; Deng, Xiaoyan; Sabo, Roy et al. (2012) Secular trends in body composition for children and young adults: the Fels Longitudinal Study. Am J Hum Biol 24:506-14
Shinnar, Shlomo; Bello, Jacqueline A; Chan, Stephen et al. (2012) MRI abnormalities following febrile status epilepticus in children: the FEBSTAT study. Neurology 79:871-7

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