Leptin levels recover normally in healthy older adults after acute diet-induced weight loss.

OBJECTIVES: Involuntary weight loss affects 20% of community dwelling older adults. The underlying mechanism for this disorder is unknown. Objective is to determine if failure of older persons to regain weight is associated with elevated pro-inflammatory cytokine and leptin levels. DESIGN: Prospective diet intervention study. SETTING: University of Washington Medical Center from 2001-2005. PARTICIPANTS: Twenty-one younger (18-35 years old) and nineteen older (>or= 70 years old) men and women. INTERVENTION: Each subject was placed for two weeks on a weight-maintaining diet, followed in sequence by 2 weeks of 30% caloric restriction, then 4 weeks of ad libitum food intake. MEASUREMENTS: Plasma leptin levels, fasting serum pro-inflammatory cytokine levels, and peripheral blood mononuclear cell cytokine levels were measured. RESULTS: Leptin levels in the two cohorts decreased after caloric restriction and increased after ad-libitum food consumption resumed. Plasma TNF alpha levels were higher in older subjects compared to younger adults. However, there was no association between changes in TNF alpha levels and changes in AUC leptin. CONCLUSION: Leptin levels in healthy older individuals responded appropriately in a compensatory manner to changes in body weight. These data do not support a cytokine dependent elevation in leptin levels as being responsible for the failure of older adults to regain weight.

Effect of endurance exercise training on heart rate variability at rest in healthy young and older men.

Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002). During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001). Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the older group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS). Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001). Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.

Neovascularization in aged mice: delayed angiogenesis is coincident with decreased levels of transforming growth factor beta1 and type I collagen.

Angiogenesis, the growth of new vessels from existing microvasculature, is delayed in aged animals. In this study we asked whether this impairment might be due, in part, to changes in the expression of a growth factor, transforming growth factor-beta1 (TGF-beta1), and a matrix protein, type I collagen, which have been shown to regulate angiogenesis in vivo. We implanted polyvinyl alcohol sponges subcutaneously in the dorsa of young and aged mice and examined the sponges 7 to 21 days later for the presence of invasive fibrovascular bundles. Blood vessel ingrowth and proliferative activity were assessed by immunostain for von Willebrand factor and Ki-67, respectively. The fibrovascular bundles were also analyzed for TGF-beta1 and type I collagen. Relative to young mice, angiogenic invasion of sponges in aged mice was similar at 7 days, was diminished significantly (70%) at 14 days, but was again similar by 21 days after implantation. The expression of TGF-beta1 and type I collagen mRNA and protein in fibrovascular bundles was coincident but was also delayed (42 to 47%) at 14 days in the aged mice. Moreover, levels of active TGF-beta1 were decreased (48%) in the sera of aged relative to young mice. The delay in angiogenesis in aged mice was thus associated with decreased expression of TGF-beta1 and type I collagen by neovascular bundles. We conclude that changes in the levels of growth factors and proteins in the extracellular matrix contribute to impaired angiogenesis in aging.

Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice.

Aged mice that have undergone long-term caloric-restriction (CR) have improved health and enhanced longevity in comparison to aged mice that are ad libitum-fed (AL). However, caloric-restriction does not benefit the impaired wound healing of aged mice. To test the hypothesis that CR mice have the capacity for enhanced wound repair, but require a short-term period of additional nutrient intake to show this advantage, we assessed wound healing in CR mice that had been refed (RF) an ad libitum diet for 4 weeks prior to wounding. Two strains of AL young (Y AL) (4-6 months), AL middle-aged (M AL) (15-17 months), and three different, matched cohorts of old mice (O) (30-33 months): O AL, O CR, and O RF were studied. Two full-thickness 4 mm diameter punch biopsy skin wounds were created on the dorsum of each mouse. Animals were sacrificed and wounds were harvested at 1,2,3,5, and 7 days post-wounding. Repair of wounds was slower in O AL and O CR mice compared to Y AL and M AL animals. In contrast, the O RF mice healed similarly to that of the Y AL and M AL mice, as assessed by measures of wound area and histologic criteria. O RF mice demonstrated enhanced synthesis of type I collagen mRNA in comparison to O AL and O CR mice. A greater number of endothelial cells and fibroblasts at the wound edge of the O RF mice exhibited replication in vivo as measured by uptake of BrdU. O RF mice had higher levels of insulin-like binding protein 3 (IGFBP-3). Furthermore, fibroblasts derived from the explant of the punch biopsy of O CR mouse skin revealed enhanced proliferation and contraction in vitro, in comparison to fibroblasts from the O AL mice. In conclusion, O RF mice demonstrate an enhanced capacity to undergo wound repair in comparison to O AL mice. This effect appears to be mediated, in part, by enhanced cell proliferation, contraction, and collagen biosynthesis. In addition, short-term refeeding induced an increase in the serum level of IGFBP-3, the major binding protein for IGF-1. These data confirm that cells from O CR animals have a preserved proliferative, biosynthetic, and contractile capacity, but that an adequate source of nutrients is necessary to demonstrate this advantage in wound healing.

Acceleration of wound healing in aged rats by topical application of transforming growth factor-beta(1).

The impaired wound healing associated with aging may reflect inadequate secretion or delivery of cytokines. Transforming growth factor-beta(1) is a mitogenic polypeptide with beneficial effects on wound healing. In the present study we questioned whether topical administration of transforming growth factor-beta(1) could improve the wound healing process in aged rats in vivo. Wound repair (from 1 to 14 days) was analyzed in full-thickness incisional wounds from 2-year-old rats with or without a single topical application of transforming growth factor-beta(1) (1 microg/wound) at the time of wounding. Identical wounds from 3-month-old, untreated rats served as controls. Histologic analysis showed a marked delay in several aspects of wound repair in the aged rats in comparison with that noted in the younger animals. Immunostaining of the wounds for proliferating cell nuclear antigen showed a reduction in the number of cycling fibroblasts in old rats. In addition, the number of capillaries per unit area of the wound as determined by a stain for Griffonin (Bandeiraea) simplicifolia lectin, and the number of inflammatory cells as identified by an antibody specific for macrophages, were also reduced in the wound area in old rats. Treatment with transforming growth factor-beta(1) resulted in marked enhancement of the following parameters: cell proliferation, inflammatory cell and fibroblast influx, wound closure, and angiogenesis. As seen with in situ hybridization, a similar temporal pattern of expression of messenger RNAs corresponding to type I procollagen and Secreted Protein, Acidic and Rich in Cysteine (osteonectin), known to be prevalent in healing wounds, was observed in both young and aged rats. However, the levels of mRNA corresponding to these secreted proteins appeared to be reduced in wound tissue from aged rats. Treatment with transforming growth factor-beta(1) subsequently resulted in an increase in the expression of both type I procollagen and Secreted Protein, Acidic and Rich in Cysteine mRNA in the wound tissue from aged rats. In summary, a single topical application of transforming growth factor-beta(1) to the wounds of aged rats at the time of wounding was associated with a healing response that, in all the parameters of wound repair examined, was similar to that of young rats. Topical transforming growth factor-beta(1) might therefore be beneficial in the treatment of dermal wounds in the aged.

Beta-adrenergic receptor downregulation and recovery in heart and lung in the Fischer 344 rat: effects of aging and correlation with mRNA levels.

Using indirect methods to downregulate beta-adrenergic receptor (BAR) density, several investigators have observed an aging-related delay in the recovery of BAR density after downregulation and suggested this finding may in part explain the decreased beta-adrenergic responsiveness associated with aging. We downregulated BAR density in male Fischer 344 rats ages 3, 12, and 24 months using the direct BAR agonist, metaproterenol. Lung and heart BAR density and BAR mRNA levels were measured daily for 5 days during recovery. Heart BAR density was downregulated significantly more in the 24-month compared to the 3-month-old animals (ANOVA p < .05). The rate of recovery of heart BAR density was greater in the 24-month compared to the 3-month-old animals (ANOVA, p = .05). Lung BAR density showed no significant age-related differences at baseline, after downregulation, or during recovery. There was no significant change in lung or heart BAR mRNA levels observed in association with downregulation of BAR density. The previously documented decrease in myocardial beta-adrenergic responsiveness with aging in this animal appears to not be related to delayed or incomplete recovery of BAR density after agonist-induced downregulation, but may be associated with greater initial downregulation of heart BAR density.

Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training.

Reduced heart rate and contractile responses to beta-agonist stimulation characterize normal cardiac aging, but whether diastolic responses also decline with aging has not been determined in humans. Diastolic filling responses to isoproterenol were determined in 13 older (60-82 yr) and 11 young (24-32 yr) healthy men before and after endurance training. Filling rates were expressed in three ways: 1) normalized to end-diastolic volume per second, 2) normalized to stroke volume per second, and 3) as absolute milliliters of blood (ml.s-1.m-2). Peak early filling rates by all methods were reduced at rest and all isoproterenol doses with aging (all P < 0.0001 for old vs. young), whereas peak atrial filling rates were increased with aging. During isoproterenol, both peak early and peak atrial filling rates increased significantly (all P < 0.01); the increase in filling rates with isoproterenol was not different with aging (all NS for old vs. young x dose). Endurance training did not augment diastolic filling responses to isoproterenol. Although diastolic filling rates at rest are markedly altered by aging, diastolic filling responses to isoproterenol are not reduced with aging. Thus the age-associated declines in heart rate, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol do not extend to diastolic filling responses.

Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men.

BACKGROUND: Cardiac aging alters many of the acute responses to exercise stress, but the extent to which chronic exercise (ie, training) can alter or improve the effects of aging in humans is largely unknown. METHODS AND RESULTS: Cardiovascular responses to graded supine exercise stress (beginning at 200 kpm and increasing by 200 kpm every 3 minutes till exhaustion) were assessed using radionuclide ventriculography in 13 older (age, 60 to 82 years) and 11 young (age, 24 to 32 years) rigorously screened healthy men before and after 6 months of endurance training. Repeated-measures ANOVA was used to test significance. During exercise, the old group had a lesser increase in heart rate (+105% old versus +166% young), a greater increase in mean blood pressure (+35% old versus +22% young), lesser increases in ejection fraction (+3 ejection fraction units old versus +11 units young) and peak ejection rate (+62% old versus +119% young), a greater increase in end-diastolic volume index (+8% old versus -10% young), a lesser fall in end-systolic volume index (-0% old versus -32% young), and a lesser increase in cardiac index (+135% old versus +189% young) (all P < .01 young/old versus exercise stage). Stroke volume index response to exercise was not different with aging (+14% old versus +6% young, P = NS). Exercise training increased maximal oxygen intake by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 mL.kg-1.min-1, P < .001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 mL.kg-1.min-1, P < .001) and increased peak workload by 24% in the old and 28% in the young. Exercise training had no differential effects on old versus young men. Among all subjects, training significantly reduced the resting heart rate by 12% (-8 beats per minute) and increased resting end-diastolic volume index by 13% (+9 mL/M2) and resting stroke volume index by 18% (+7 mL/M2) (all P < .01). At peak exercise, cardiac index increased by 16% (+1.07 L.M-2.min-1) compared with before training, which was the result of an increase in stroke volume of 18% (+7 mL/M2) (P < .001); peak heart rate was unchanged. The increase in stroke volume index at peak exercise was the result of both a 12% increase in end-diastolic volume index (+8 mL/M2) (P < .01) and an increase in ejection fraction (+3 ejection fraction units) (P < .05) at peak exercise. The increased ejection fraction at peak exercise occurred despite a 9% increase in systolic blood pressure (+18 mm Hg) (P < .01), suggesting an increase in contractility. Thus, both the young and old increased peak exercise cardiac output by use of the Frank-Starling mechanism (ie, cardiac dilatation) as well as an increase in ejection fraction. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, ejection fraction, and cardiac output responses to supine exercise in healthy men. Although the stroke volume responses of the young and old are similar, the old tend to augment stroke volume during exercise more through cardiac dilatation, with an increase in end-diastolic volume (+8%) but without much change in ejection fraction (+3 ejection fraction units), whereas the young rely more on an increase in the ejection fraction (+11 ejection fraction units) with no cardiac dilatation (-10%). Despite the significant cardiovascular changes that occur in the response to a single bout of exercise with aging, adaptations to chronic exercise training were not different with aging and included improvements in maximal workload and increases in ejection fraction, stroke volume index, and cardiac index at peak exercise.

TGF-beta 1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors.

Fibroblasts have a major role in the synthesis and reorganization of extracellular matrix that occur during wound repair. An impaired biosynthetic or functional response of these cells to stimulation by growth factors might contribute to the delayed wound healing noted in aging. We, therefore, compared the responses of dermal fibroblasts from young and elderly individuals (26, 29, 65, 89, 90, and 92 years of age) to transforming growth factor-beta 1 (TGF-beta 1) with respect to: (1) the synthesis of type I collagen and SPARC (two extracellular matrix proteins that are highly expressed by dermal fibroblasts during the remodeling phase of wound repair) and (2) the contraction of collagen gels, and in vitro assay of wound contraction. With the exception of one young donor, all cultures exposed for 44 hours to 10 ng/ml TGF-beta 1 exhibited a 1.6- to 5.5-fold increase in the levels of secreted type I collagen and SPARC, relative to untreated cultures, and exhibited a 2.0- to 6.2-fold increase in the amounts of the corresponding mRNAs. Moreover, the dose-response to TGF-beta 1 (0.1-10 ng/ml), as determined by synthesis of type I collagen and SPARC mRNA, was as vigorous in cells from aged donors as in cells from a young donor. In assays of collagen gel contraction, fibroblasts from all donors were stimulated to a similar degree by 10 ng/ml TGF-beta 1. In conclusion, cells from both young and aged donors exhibited similar biosynthetic and contractile properties with exposure to TGF-beta 1. It therefore appears that the impaired wound healing noted in the aged does not result from a failure of their dermal fibroblasts to respond to this cytokine.

Endurance exercise training augments diastolic filling at rest and during exercise in healthy young and older men.

BACKGROUND: Diastolic filling at rest is altered markedly with advancing age. Whether exercise training can improve diastolic filling at rest or during exercise in either healthy older or healthy young men has not been determined. The purpose of this study was to determine if 6 months of aerobic exercise training improves diastolic filling. METHODS AND RESULTS: Radionuclide diastolic filling parameters were measured at rest and during exercise in 14 older (age, 60 to 82 years) and 17 young (age, 24 to 32 years) rigorously screened healthy males before exercise training and in 13 older and 11 young men after 6 months of endurance exercise training. Diastolic filling rates were expressed in two ways, as absolute milliliters of blood (mL.s-1.m-2) and normalized to the end-diastolic volume. At baseline, the peak early filling rates were lower in the older group compared with the young group as expressed in absolute milliliters of blood (older, 85 +/- 7 mL.s-1.m-2; young, 173 +/- 10 mL.s-1.m-2; P < or = .0001) and in end-diastolic volume per second (1.66 +/- 0.11 versus 2.55 +/- 0.08, P < .0001), whereas the peak atrial filling rates were greater in absolute milliliters of blood (85 +/- 5 versus 56 +/- 7 mL.s-1.m-2, P = .003) and in end-diastolic volume per second (1.70 +/- 0.12 versus 0.80 +/- 0.06, P < .0001). During exercise, at any given heart rate, the older group had a lower peak filling rate than the young group. Also, at peak exercise, the single peak filling rate was decreased in the older group in mL.s-1.m-2 (384 +/- 19 versus 565 +/- 36 mL.s-1.m-2, P = .0002) and in end-diastolic volume per second (6.01 +/- 0.25 versus 7.91 +/- 0.28 end-diastolic volume per second, P < .0001). Six months of intensive aerobic exercise training had similar effects in the old and young groups overall. Maximal oxygen consumption increased 19% (ANOVA training effect, P < or = .0001) and echocardiographic left ventricular mass increased 8% (ANOVA training effect, P = .002). Training increased the resting peak early filling rate in absolute milliliters of blood by +14% (ANOVA training effect, P = .02). During exercise, the peak early or single peak filling rate at any given heart rate was increased. At peak exercise, the single peak filling rate was increased by 14% in mL.s-1.m-2 (ANOVA training effect, P = .0004). The only age-related differential effect of training was on the peak atrial filling rate in end-diastolic volume per second, which decreased by 27% in the older group but was unchanged in the young (+5%) (ANOVA young versus older, P = .001). The independent predictors of a greater maximal oxygen consumption by multivariate analysis were a higher peak exercise heart rate, a greater resting peak early filling rate, the exercise trained state, and a younger age. CONCLUSIONS: Healthy older men have reduced early diastolic filling at rest and during exercise compared with young men. Endurance exercise training enhances early diastolic filling at rest and during exercise in both the old and the young. Training reduces the elevated resting atrial filling rate in the old, whereas the young were unchanged. The training-induced augmentation of early diastolic filling at rest and during exercise may be an important adaptation to allow an increase in stroke volume at rest and an increase in stroke volume, cardiac output, and maximal oxygen consumption during exercise.

The Seattle FICSIT/MoveIt study: the effect of exercise on gait and balance in older adults.

While exercise is generally recommended for older adults, the specific role of exercise in preventing falls and frail health is unclear. The Seattle FICSIT/MoveIt study is a population-based, randomized, controlled trial comparing the effects of three 6-month exercise interventions (endurance training, strength training, or combined endurance and strength training), and three 3-month endurance training interventions (stationary cycle, walking, or aerobic movement). Primary study outcomes are aerobic capacity, strength, gait, balance, and physical functional status. The study enrolls adults age 68-85 who have leg weakness and impaired gait. It differs from most previous community-based exercise studies in several respects: recruitment of subjects from a defined population; eligibility criteria based upon physiologic and functional status deficits; random assignment to exercise groups; assessment of both physiologic and functional status outcomes; follow-up beyond the completion of supervised exercise; and a large sample size (Total N = 180).

Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.

BACKGROUND: Cardiac aging is characterized by a reduced heart rate response to beta-agonist stimulation with isoproterenol, but whether the ejection fraction and other cardiovascular responses are reduced in humans is largely unknown. In addition, whether reduced beta-agonist responses can be improved with exercise training has not been determined in humans. METHODS AND RESULTS: Cardiovascular responses to graded isoproterenol infusions (3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15 older (age, 60-82 years) and 17 young (age, 24-32 years) rigorously screened healthy men. Thirteen older and 11 young subjects completed 6 months of endurance training and were retested. At baseline, the older group had reduced responses to isoproterenol for heart rate (+65% older versus +92% young, p less than 0.001), systolic blood pressure (+9% versus +24%, p less than 0.001), diastolic blood pressure (-12% versus -24%, p less than 0.05), ejection fraction (+12 versus +20 ejection fraction units, p less than 0.001), and cardiac output (+70% versus +100%, p less than 0.001). The mean plasma isoproterenol concentrations achieved during the infusions were marginally higher (p = 0.07) in the older group (128 +/- 58, 227 +/- 64, 354 +/- 114, and 700 +/- 125 pg/ml) than in the young (79 +/- 20, 178 +/- 49, 273 +/- 79, and 571 +/- 139 pg/ml). Intensive training increased maximal oxygen consumption by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 ml/kg/min, p less than 0.001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 ml/kg/min, p less than 0.001), but training did not augment any of the cardiovascular responses to isoproterenol in either group. The mean plasma isoproterenol concentrations at the four infusion doses were unchanged after training in both groups. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, blood pressure, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol in healthy men. Altered beta-adrenergic responses probably contribute to the reduced cardiac responses to maximal exercise that also occur with aging. Furthermore, intensive exercise training does not increase cardiac responses to beta-adrenergic stimulation with isoproterenol in either young or older men. The reduced beta-adrenergic response appears to be a primary age-associated change that is not caused by disease or inactivity.

Effect of intensive endurance training on lipoprotein profiles in young and older men.

Although there are considerable data concerning the effects of endurance exercise training (ET) on plasma lipoproteins, the results have been quite inconsistent. The observed variability of response may be related to the age, sex, adiposity, or diet of the subjects tested, or to the type and intensity of the exercise intervention. Furthermore, there is relatively little such data in older individuals. Therefore, in the present study, we investigated the effects of intensive ET on lipoprotein profiles in healthy young (n = 12; 28.2 +/- 2.4 years) and older (n = 15; 67.5 +/- 5.8 years) men. Unlike subjects in most similar studies, our subjects were weight-stabilized on a constant-composition diet for 21 days prior to determination of the lipoprotein profile before and after the ET program. At baseline, the two groups were not significantly different with respect to any individual component of their lipoprotein profiles, relative weight, or percent body fat, but the older men had a more central distribution of fat by both waist to hip ratio (WHR) and computed tomography (CT). Maximal aerobic power, expressed per kilogram of body weight (VO2 max), was 33% lower (P less than .001) in the older men at baseline. Following the 6-month, walk/jog/bike ET program (5 d/wk), both the young (+18%, P less than .001) and the older (+22%, P less than .001) men increased their VO2 max. This was associated with small, but significant, decrements in weight, percent body fat, and WHR only in the older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging.

Aging has been associated with glucose intolerance, insulin resistance, hyperinsulinemia, and diminished islet B-cell function. The relative contribution of these factors to the aging-associated changes in glucose tolerance has been difficult to discern, particularly so for B-cell function, since insulin sensitivity itself is a determinant of B-cell function and, therefore, comparisons of insulin levels and responses between old and young subjects are difficult. To reduce this effect, we compared B-cell function in 14 healthy older men (aged 61-82 yr; body mass index, 21-30 kg/m2), who were exercise trained for 6 months to improve insulin sensitivity, to that of 11 healthy young men (aged 24-31 yr; body mass index, 19-31 kg/m2), who were also trained. Insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness at zero insulin (GEZI) using Bergman's minimal model. B-Cell function was assessed by determining the acute insulin responses (AIR) to glucose (AIRgluc) and arginine at 3 different glucose levels: fasting, approximately 14 mM, and greater than 28 mM (AIRmax). AIRmax provides a measure of B-cell secretory capacity, while the glucose level at which 50% of AIRmax occurs is termed PG50 and is used to estimate B-cell sensitivity to glucose. The insulin sensitivity and glucose effectiveness at zero insulin of the trained older subjects was similar to that of the trained young [SI: old, 5.1 +/- 0.6; young, 6.5 +/- 0.7 x 10(-5) min-1/pM (mean +/- SEM; P = NS); GEZI: old, 1.3 +/- 0.2; young, 1.7 +/- 0.2 x 10(-2) min (P = NS)]. Under these conditions, the fasting glucose levels (old, 5.4 +/- 0.2; young, 5.1 +/- 0.1 mM) and basal insulin levels (old, 49 +/- 6; young, 63 +/- 11 pM) were also similar in the two groups. AIRgluc values were lower in the exercised elderly (old, 253 +/- 50; young, 543 +/- 101 pM; P = 0.01). This decrease in stimulated insulin release was due solely to a reduction in the AIRmax (old, 1277 +/- 179; young, 2321 +/- 225 pM; P less than 0.005); the PG50 was not different (old, 8.9 +/- 0.4; young, 8.8 +/- 0.2 mM; P = NS). These differences in the older subjects were associated with a reduction in iv glucose tolerance (old, 1.49 +/- 0.15; young, 1.95 +/- 0.13%/min; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of intensive endurance exercise training on body fat distribution in young and older men.

Little is known about the effects of exercise interventions on the distribution of central and/or intra-abdominal (IA) fat, and until now there were no studies in the elderly. Therefore, in this study we investigated the effects of an intensive 6-month endurance training program on overall body composition (hydrostatic weighing), fat distribution (body circumferences), and specific fat depots (computed tomography [CT]), in healthy young (n = 13; age, 28.2 +/- 2.4 years) and older (n = 15; age, 67.5 +/- 5.8 years) men. At baseline, overall body composition was similar in the two groups, except for a 9% smaller fat free mass in the older men (P less than .05). The thigh and arm circumferences were smaller (P = .001 and P less than .05, respectively), while the waist to hip ratio (WHR) was slightly greater in the older men (0.92 +/- 0.04 v 0.97 +/- 0.04, P less than .01). Compared with the relatively small baseline differences in body composition and circumferences, CT showed the older men to have a twofold greater IA fat depot (P less than .001), 48% less thigh subcutaneous (SC) fat (P less than .01), and 21% less thigh muscle mass (P less than .001). Following endurance (jog/bike) training, both the young (+18%, P less than .001) and the older men (+22%, P less than .001) significantly increased their maximal aerobic power (VO2max). This was associated with small but significant decrements in weight, percent body fat, and fat mass (all P less than .001) only in the older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults.

BACKGROUND: The effects of 6 months of intensive endurance exercise training on resting tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, t-PA antigen, and fibrinogen were studied in 10 young (24-30 years) and in 13 old male subjects (60-82 years). METHODS AND RESULTS: After training, maximum oxygen consumption was increased in the young group by 18% (44.9 +/- 5.0 to 52.9 +/- 6.6 ml/kg/min, p less than 0.001), whereas it was increased in the old group by 22% (29.0 +/- 4.2 to 35.5 +/- 3.6 ml/kg/min, p less than 0.001). The young group had no significant changes in any of the measured variables, whereas the old group had a 39% increase in t-PA activity (0.82 +/- 0.47 to 1.14 +/- 0.42 IU/ml, p less than 0.03), a 141% increase in the percentage of t-PA in the active form (11.1 +/- 7.7 to 26.8 +/- 15.1%, p less than 0.01), a 58% decrease in PAI-1 activity (8.4 +/- 4.9 to 3.5 +/- 1.7 AU/ml, p less than 0.01), and a 13% decrease in fibrinogen (3.57 +/- 0.79 to 3.11 +/- 0.52 g/l, p less than 0.01). CONCLUSIONS: We conclude that intensive exercise training enhances resting t-PA activity and reduces fibrinogen and PAI-1 activity in older men. These effects are potential mechanisms by which habitual physical activity might reduce the risk of cardiovascular disease.