We plan to analyze the data set generated by 2567 participants in the Fels Longitudinal Study over a period of eight decades in order to ascertain if certain putative juvenile protective factors and juvenile protective states can delay the onset of age related disease (ARD) and increase longevity in subjects who retain juvenile levels of such protective factors and states in adulthood. Although it is possible to age in good health, obesity, hypertension (HBP), dyslipidemia, and impaired fasting glucose are frequent concomitants of aging, as well as type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), cancer, and osteoporosis (OP). These conditions all increase in prevalence with age, and age is the primary risk factor for cancer, CVD, and osteoporotic fractures. The putative JPF we plan to study are adiponectin, osteocalcin, and insulin-like growth factor-1 binding protein 3 (IGF1BP3). There is evidence in the literature that these putative JPF are associated with either enhanced survival and/or a delay in the onset of ARD. A defining attribute of a JPF is that it could theoretically be replenished from exogenous sources to re-establish juvenile levels in the circulation in order to engender a delay in the onset of ARD or even to reverse established ARD. Unlike JPF, JPS could not be added to the circulation from exogenous sources. However, significant changes in JPS can be attained by life-style and/or pharmacologic means. Therefore, we will examine the effects of persistence of juvenile levels of these protective states in FLS adult participants on te onset of ARD. The putative JPS we plan to study include high fat-free mass/ht2 (FFM/ht2), high insulin sensitivity high HDL- cholesterol, and low systolic and/or diastolic blood pressure (SBP/DBP. Should we confirm that some or all of these JPF and JPS are associated with a delayed onset of ARD and/or with an extended life span, our findings may be applied in clinical assessments of individuals whose JPF and JPS trajectories diverge from those that predict delayed onset of ARD. It may also be possible to develop novel therapies based on maintaining or restoring juvenile levels of these protective factors and states in adulthood to delay the onset of ARD or reverse established ARD. We recognize that major logistic and regulatory hurdles must be cleared before such novel preventive or therapeutic approaches can be applied.

Public Health Relevance

of this research to public health. Age-related diseases (i.e. the metabolic syndrome, hypertension, type 2 diabetes mellitus, and cardiovascular disease, cancer, and osteoporosis) shorten the life span of affected individuals and cost several hundred billion dollars every year in medical care and human capital. Our analyses of the database of the 85-year-old Fels Longitudinal Study should reveal the existence of juvenile protective factors and may pave the way to developing interventions that lengthen the period of time during which adults remain free of age-related disease. Eventually these analyses may lead to reversing age-related disease by restoring juvenile levels of protective factors in affected adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG048801-04
Application #
9701067
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Dutta, Chhanda
Project Start
2016-08-15
Project End
2020-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
4
Fiscal Year
2019
Total Cost
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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