Aging is associated with a decrease in metabolic function which increases the likelihood of hyperlipidemia and glucose intolerance. In addition, cardiac reserve function (quantified as maximal aerobic capacity, VO2 max) declines with advancing age. These functional changes increase risk for coronary artery disease (CAD). The basic hypothesis of this proposal is that declines in metabolic function are not solely due to primary biological aging but occur predominantly due to secondary processes such as physical inactivity, obesity, and chronic disease. To determine the independent effects of physical activity on lipoprotein and glucose metabolism in older men, the other secondary processes must be controlled. Men of comparable age (60-75 yrs) and percent body fat (determined by hydrodensitometry) will be screened for overt and chronic disease. Occult CAD will be excluded by exercise stress tests and thallium scans. Metabolic dysfunction will be screened by glucose tolerance tests and lipoprotein profiles. Healthy, lean (less than 21% body fat), sedentary (VO2 max: 20-30 ml/kg/min) and highly conditioned (V02 max: 50-60 ml/kg/min) men will be selected for study. The regulation of lipoprotein metabolism will be determined by measuring fasted and postprandial (oral fat meal) levels of lipoprotein (VLDL, LDL, HDL) lipids and HDL subspecies, lipoprotein lipase and hepatic lipase activities, and VLDL triglyceride kinetics. The mechanisms regulating glucose metabolism will be determined by measuring insulin sensitivity and secretion and hepatic glucose production using the hyperglycemic and euglycemic clamp with radioisotope tracer studies. The effects of change in physical conditioning status, (defined by change in V02 max), on metabolic function will be assessed by implementing an aerobic exercise training program for the sedentary subjects and deconditioning the physically active men. The baseline metabolic testing will then be repeated. Analysis of results by paired t tests and regression analysis will differentiate between effects of physical deconditioning vs primary aging and determine the mechanisms by which altered conditioning status effects glucose and lipoprotein metabolism in older men. This may have important medical and socioeconomic implications for the prevention of CAD in this population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG000383-05
Application #
3078578
Study Section
Special Emphasis Panel (GER)
Project Start
1987-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Goldberg, A P; Busby-Whitehead, M J; Katzel, L I et al. (2000) Cardiovascular fitness, body composition, and lipoprotein lipid metabolism in older men. J Gerontol A Biol Sci Med Sci 55:M342-9
Katzel, L I; Fleg, J L; Busby-Whitehead, M J et al. (1998) Exercise-induced silent myocardial ischemia in master athletes. Am J Cardiol 81:261-5
Yataco, A R; Busby-Whitehead, J; Drinkwater, D T et al. (1997) Relationship of body composition and cardiovascular fitness to lipoprotein lipid profiles in master athletes and sedentary men. Aging (Milano) 9:88-94
Nicklas, B J; Katzel, L I; Busby-Whitehead, J et al. (1997) Increases in high-density lipoprotein cholesterol with endurance exercise training are blunted in obese compared with lean men. Metabolism 46:556-61
Katzel, L I; Busby-Whitehead, M J; Hagberg, J M et al. (1997) Abnormal exercise electrocardiograms in master athletes after three months of deconditioning. J Am Geriatr Soc 45:744-6
Katzel, L I; Busby-Whitehead, M J; Rogus, E M et al. (1994) Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia. Metabolism 43:190-8
Katzel, L I; Sorkin, K D; Colman, E et al. (1994) Risk factors for exercise-induced silent myocardial ischemia in healthy volunteers. Am J Cardiol 74:869-74
Busby, J; Tobin, J; Ettinger, W et al. (1991) A longitudinal study of osteoarthritis of the hand: the effect of age. Ann Hum Biol 18:417-24
Gloth 3rd, F M; Busby, M J (1989) Methyldopa-induced diarrhea: a case of iatrogenic diarrhea leading to request for nursing home placement. Am J Med 87:480-1
Busby, M J; Shefrin, E A; Fleg, J L (1989) Prevalence and long-term significance of exercise-induced frequent or repetitive ventricular ectopic beats in apparently healthy volunteers. J Am Coll Cardiol 14:1659-65

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