Wendy M. Kohrt

Effects of aging, sex, and physical training on cardiovascular responses to exercise.

BackgroundThe relative contributions of decreases in maximal heart rate, stroke volume, and oxygen extraction and of changes in body weight and composition to the age-related decline in maximal oxygen uptake (V˙o2max) are unclear and may be influenced by sex and level of physical activity. Methods and ResultsTo investigate mechanisms by which aging, sex, and physical activity influence V˙o2max, we quantified V˙o2, cardiac output, and heart rate during submaximal and maximal treadmill exercise and assessed weight and fat-free mass in healthy younger and older sedentary and endurance exercise-trained men and women. For results expressed in milliliters per kilogram per minute, a three-to-four-decade greater age was associated with a 40–41% lower V˙o2max in sedentary subjects and a 25–32% lower V˙o2max in trained individuals (p < 0.001). A smaller stroke volume accounted for nearly 50%o of these age-related differences, and the remainder was explained by a lower maximal heart rate and reduced oxygen extraction (all p < 0.001). Age-related effects on maximal heart rate and oxygen extraction were attenuated in trained subjects (p < 0.05). After normalization ofV˙o2max and maximal cardiac output to fat-free mass, age- and training-related differences were reduced by 24–47% but remained significant (p < 0.05). For trained but not sedentary subjects, maximal cardiac output and stroke volume normalized to fat-free mass were greater in men than in women (p < 0.05). ConclusionsA lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise all contribute to the age-related decline in V˙o2max. Effects of age and training on V˙o2max, maximal cardiac output, and stroke volume cannot be fully explained by differences in body composition. In sedentary subjects, however, the sex difference in maximal cardiac output and stroke volume can be accounted for by the greater percentage of body fat in women than in men.

Insulin Resistance in Aging Is Related to Abdominal Obesity

Studies have shown that insulin resistance increases with age, independent of changes in total adiposity. However, there is growing evidence that the development of insulin resistance may be more closely related to abdominal adiposity. To evaluate the independent effects of aging and regional and total adiposity on insulin resistance, we performed hyperinsulinemic euglycemic clamps on 17 young (21–33 yr) and 67 older (60–72 yr) men and women. We assessed FFM and total and regional adiposity by hydrodensitometry and anthropometry. Insulin-stimulated GORs at a plasma insulin concentration of ∼450 pM averaged 45.6 ± 3.3 μmol · kg FFM−1 · min−1 (mean ± SE) in the young subjects, 45.6 ± 10.0 μmol · kg FFM−1 · min−1 in 24 older subjects who were insulin sensitive, and 23.9 ± 11.7 μmol · kg FFM−1 · min−1 in 43 older subjects who were insulin resistant. Few significant differences were apparent in skin-fold and circumference measurements between young and insulin-sensitive older subjects, but measurements at most central body sites were significantly larger in the insulin-resistant older subjects. Waist girth accounted for >40% of the variance in insulin action, whereas age explained only 10–20% of the total variance and <2% of the variance when the effects of waist circumference were statistically controlled. These results suggest that insulin resistance is more closely associated with abdominal adiposity than with age.

Effects of Exercise Involving Predominantly Either Joint‐Reaction or Ground‐Reaction Forces on Bone Mineral Density in Older Women

This study compared the effects of two exercise training programs, 11 months in duration, on bone mineral density (BMD) in older, sedentary women. Thirty‐nine women, aged 60–74 years, were assigned to the following groups: (a) a group that performed exercises that introduced stress to the skeleton through ground‐reaction forces (GRF) (i.e., walking, jogging, stairs); (b) a group that performed exercises that introduced stress to the skeleton through joint‐reaction forces (JRF) (i.e., weight lifting, rowing); or (c) a no‐exercise control group. BMD of the whole body, lumbar spine, proximal femur, and distal forearm was assessed five times at ∼3‐month intervals. The GRF and JRF exercise programs resulted in significant and similar increases in BMD of the whole body (2.0 ± 0.8% and 1.6 ± 0.4%, respectively), lumbar spine (1.8 ± 0.7% and 1.5 ± 0.5%, respectively), and Wards triangle region of the proximal femur (6.1 ± 1.5% and 5.1 ± 2.1%, respectively). There was a significant increase in BMD of the femoral neck only in response to the GRF exercise program (GRF, 3.5 ± 0.8%; JRF, −0.2 ± 0.7%). There were no significant changes in BMD in control subjects. Among all exercisers, there was a significant inverse (r = −0.52, p < 0.01) relationship between increases in whole body BMD and reductions in fat mass, suggesting a dose response effect of exercise on bone mass. Although femoral neck BMD was responsive only to the GRF exercise program, some adaptations (i.e., increase in lean body mass and strength) that were specific to the JRF exercise program may be important in preventing osteoporotic fractures by reducing the risk for falls. It remains to be determined whether all of these benefits can be gained through a training program that combines the different types of exercises employed in this study.

The Ratio of Waist-to-Hip Circumference, Plasma Insulin Level, and Glucose Intolerance as Independent Predictors of the HDL2 Cholesterol Level in Older Adults

High plasma levels of HDL2, a subfraction of high-density lipoprotein (HDL) cholesterol, are associated with a reduced risk of coronary heart disease. To investigate the characteristics related to HDL2 cholesterol levels, we measured lipoprotein levels and several metabolic and anthropometric variables in 146 healthy subjects (77 men and 69 women) in the seventh decade of life. The level of HDL2 cholesterol was inversely correlated with the ratio of the waist-to-hip circumference (r = -0.335 for men; r = -0.370 for women; P less than 0.01) and the plasma insulin level (r = -0.400 for men; r = -0.398 for women; P less than 0.001). In a multiple regression model including both sexes, 41 percent of the variance in the HDL2 level was explained by the combined effect of the waist-to-hip ratio (P less than 0.0001), the plasma insulin level (P = 0.0003), and the degree of glucose tolerance indicated by the integrated area under the plasma glucose curve after an oral glucose-tolerance test (P = 0.05). The body-mass index, total percentage of body fat, maximal oxygen uptake, diet, and sex were not significant predictors of the HDL2 level when added to this model, whereas the original variables remained significant predictors. The HDL2 cholesterol level in subjects at the 25th percentile for waist-to-hip ratio was 153 percent of that in subjects at the 75th percentile. We conclude that HDL2 levels are inversely correlated with truncal fat, plasma insulin levels, and the presence of glucose intolerance and are not independently associated with sex or total body fat.

Effects of DHEA replacement on bone mineral density and body composition in elderly women and men.

Dehydroepiandrosterone (DHEA) is a precursor for both oestrogens and androgens. Its marked decline with ageing may influence age‐related changes in tissues influenced by sex hormones. The aim of this study was to determine the effects of DHEA replacement on bone mineral density (BMD) and body composition in elderly women and men with low serum DHEA sulphate (DHEAS) levels.

Effects of aging, gender, and physical training on peripheral vascular function

BackgroundBlood pressure and total peripheral resistance increase with age. However, the effect of age on vasodilatory capacity has not been characterized. Methods and ResultsTo delineate the effects of aging, gender, and physical training on peripheral vascular function, we measured blood pressure during submaximal and maximal treadmill exercise and measured blood pressure, calf blood flow, and calf conductance (blood flow/mean blood pressure) at rest and during maximal hyperemia in 58 healthy sedentary subjects (men aged 25 ± 5 and 65 ± 3 years and women aged 27 ± 5 and 65 ± 4 years) and in 52 endurance exercise-trained subjects (men aged 30 ± 3 and 65 ± 4 years and women aged 27 ± 3 and 65 ± 3 years). Systolic and mean blood pressures were higher at rest, during maximal calf hyperemia, and during submaximal exercise of the same intensity in the older than in the younger subjects of the same gender and exercise training status (p < 0.01). The magnitude of the age-related effect on blood pressure during exercise was greater in women than in men (p < 0.01). Diastolic blood pressure during submaximal exercise was also higher in the older than in the younger subjects (p < 0.05) but not in women treated with estrogen replacement. In contrast, systolic and mean blood pressures during submaximal work were lower in physically conditioned subjects than in sedentary age- and gender-matched subjects (p < 0.05) but not in older women. Increased age was associated with reduced maximal calf conductance in women (p < 0.01) but not in men. However, calf vasodilatory capacity was higher in trained than in untrained subjects (p < 0.01), regardless of age and gender. There was a significant inverse relation between maximal calf conductance and systolic, diastolic, and mean blood pressures during submaximal exercise (r = −0.31 to −0.53, p < 0.01) and a direct relation between maximal calf conductance and maximal oxygen uptake (r =0.66, p < 0.0001). ConclusionsThus, for healthy subjects between the ages of 25 and 65 years, there is an interactive effect between age and gender and an independent effect of physical -training on peripheral vascular function.

Effects of hormone replacement therapy on cognitive performance in elderly women

OBJECTIVEnTo determine the effects of 9 months of hormone replacement therapy (HRT) on cognitive performance in women aged 75 years and older.nnnMETHODSnA 9-month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two elderly postmenopausal women (age range 75-91 years) without known contraindications to HRT or evidence of dementia or depression were enrolled. Participants were randomly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days (HRT). Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests: Verbal Fluency Test, Weschler Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests, Cancellation Random Letter and Random Form Tests.nnnRESULTSnAt baseline, women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy, but otherwise did not differ from women in the placebo group. After 9 months of treatment, there were no significant group differences for any of the cognitive performance measures. The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause, education, and previous hysterectomy.nnnCONCLUSIONSnAlthough conclusions are limited by small sample size and the relatively short duration of treatment, results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression.

Effects of endurance exercise and hormone replacement therapy on serum lipids in older women

OBJECTIVE: To determine the effects of 11 months of exercise training and hormone replacement therapy (HRT), alone or in combination, on serum lipids and lipoproteins, in postmenopausal women.

Waist circumference vs body mass index for prediction of disease risk in postmenopausal women.

OBJECTIVE: To test the sensitivity of waist circumference (central adiposity) as an index of disease risk in postmenopausal women.DESIGN: Retrospective analysis of postmenopausal women tested at Washington University School of Medicine.SUSBJECTS: A total of 323 healthy postmenopausal (66±5u2005y; mean±s.d.) women not using any hormone replacement.MEASUREMENTS: Body composition, hyperinsulinemia (insulin area), triglycerides and HDL-cholesterol.RESULTS: Excess waist size had a stronger association with hyperinsulinemia and hypertriglyceridemia than body mass index (BMI; kg/m2) in otherwise healthy, postmenopausal women. After adjusting for BMI, a strong relation existed between waist circumference and insulin area, HDL-cholesterol and triglycerides (P<0.01). Conversely, after adjusting for waist circumference, no relation was apparent between BMI and the dependent variables of interest. The strength of the association between waist circumference and disease risk became most apparent when analyses were restricted to normal-weight women (BMI 24–28u2005kg/m2). When BMI was held constant, hyperinsulinemia and triglyceridemia increased dose-dependently with changes in waist size.CONCLUSION: Waist circumference, an easily obtained index of central adiposity, is a more sensitive measure of relative disease risk than is BMI in middle-aged and older women, particularly in normal-weight individuals.

Effect of exercise training on left ventricular performance in older women free of cardiopulmonary disease

Endurance exercise training increases aerobic exercise capacity (maximal oxygen consumption rate [VO2max]) and attenuates the age-related decline in left ventricular (LV) function during exercise in older men. To determine whether similar adaptations occur in older women, 10 subjects (aged 63 +/- 4 years mean +/- SE) were studied before and after 9 to 12 months of endurance exercise training. They exercised 3.85 +/- 0.06 days/week at 81 +/- 0.3% of maximal heart rate. LV function at rest and during supine exercise was assessed by radionuclide ventriculography. VO2max was increased by 21% (from 1.40 +/- 0.1 to 1.7 +/- 0.1 liter/min; p < 0.001) in response to training. Maximal heart rate and systolic blood pressure during treadmill exercise were unchanged (161 +/- 5 beats/min before vs 164 +/- 3 beats/min after; p = NS, and 208 +/- 7 mm Hg before vs 214 +/- 8 mm Hg after; p = NS, respectively) after training. LV ejection fraction at rest (70.4 +/- 2% before vs 70 +/- 1% after) and during peak exercise (78.6 +/- 2% before vs 79.3 +/- 2% after) did not change in response to training. Furthermore, the increases in ejection fraction from rest to exercise were similar before and after training (change: 8.8 +/- 1 vs 9.1 +/- 1%). Stroke volume and cardiac output at peak exercise also did not change in response to training.(ABSTRACT TRUNCATED AT 250 WORDS)