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Purpose-The purpose of this study was to examine the relationship of exercise energy expenditure (EEE) with both telomere length and telomerase activity in addition to accounting for hTERT C-1327T promoter genotype.Methods-Sixty-nine (n = 34 males; n = 35 females) participants 50-70 yr were assessed for weekly EEE level using the Yale Physical Activity Survey. Lifetime consistency of EEE was also determined. Subjects were recruited across a large range of EEE levels and separated into quartiles: 0-990, 991-2340, 2341-3540, and 93541 kcalIwk j1 . Relative telomere length and telomerase activity were measured in peripheral blood mononuclear cells (PBMC).Results-The second EEE quartile exhibited significantly longer telomere lengths [1.12 T 0.03 relative units (RU)] than both the first and fourth EEE quartiles (0.94 T 0.03 and 0.96 T 0.03 RU, respectively; P G 0.05) but was not different from the third quartile. Telomerase activity was not different among the EEE quartiles. An association was observed between telomerase enzyme activity and hTERT genotype with the TT genotype (1.0 • 10 j2 T 4.0 • 10 j3 attomoles (amol) per 10,000 cells; n = 19) having significantly greater telomerase enzyme activity than both the CT (1.3 • 10 j3 T 3.2 • 10 j3 ; n = 30) and CC groups (5.0 • 10 j4 T 3.9 • 10 j3 ; n = 20; P = 0.01).Conclusion-These results indicate that moderate physical activity levels may provide a protective effect on PBMC telomere length compared with both low and high EEE levels. Keywords TELOMERE BIOLOGY; EXERCISE ENERGY EXPENDITURE; hTERT GENOTYPE; GENETICS; DNAPhysical activity (PA) and increased physical fitness are known to decrease the likelihood of morbidity and mortality from a variety of causes (e.g., reduced cardiovascular disease (CVD), insulin resistance, and hypertension) (6), with concomitant increases in longevity (21). Whereas the reduction of disease end points will necessarily increase longevity, whether PA also directly affects cellular aging remains unclear for either rodents or humans (7). Telomere length is a primary biomarker of cellular aging that has recently been associated with CVD (1), insulin resistance and hypertension (14), and morbidity and mortality (9). In the present study, we explored the correlation of PA levels with telomere length and telomerase enzyme activity.Address for correspondence: Stephen M. Roth, Ph.D., 2134 SPH Bldg, Department of Kinesiology, University of Maryland, College Park, MD 20742-2611; E-mail: sroth1@umd.edu.. Telomeres are found on the ends of linear chromosomes and act as a mitotic clock (18), which shortens with every cell division until cellular senescence. Thus, telomeres are considered an important aging biomarker (2,4). Telomeres and their length are not, however, static entities but rather are a dynamic system (4). In certain cells, the ribonucleoprotein, telomerase, maintains and lengthens telomeres, allowing continued mitotic activity without progression to senescence (5). In cells with telomerase activity, telomere length can be maintain...

Orthostatic tolerance is reduced in the heat-stressed human. The purpose of this project was to identify whether skin-surface cooling improves orthostatic tolerance. Nine subjects were exposed to 10 min of 60° head-up tilting in each of four conditions: normothermia (NT-tilt), heat stress (HT-tilt), normothermia plus skin-surface cooling 1 min before and throughout tilting (NT-tiltcool), and heat stress plus skin-surface cooling 1 min before and throughout tilting (HT-tiltcool). Heating and cooling were accomplished by perfusing 46 and 15°C water, respectively, though a tube-lined suit worn by each subject. During HT-tilt, four of nine subjects developed presyncopal symptoms resulting in the termination of the tilt test. In contrast, no subject experienced presyncopal symptoms during NT-tilt, NT-tiltcool, or HT-tiltcool. During the HT-tilt procedure, mean arterial blood pressure (MAP) and cerebral blood flow velocity (CBFV) decreased. However, during HT-tiltcool, MAP, total peripheral resistance, and CBFV were significantly greater relative to HT-tilt (all P< 0.01). No differences were observed in calculated cerebral vascular resistance between the four conditions. These data suggest that skin-surface cooling prevents the fall in CBFV during upright tilting and improves orthostatic tolerance, presumably via maintenance of MAP. Hence, skin-surface cooling may be a potent countermeasure to protect against orthostatic intolerance observed in heat-stressed humans.

We tested the hypothesis that women have blunted sympathetic neural responses to orthostatic stress compared with men, which may be elicited under hypovolemic conditions. Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in eight healthy young women and seven men in supine position and during 6 min of 60 degrees head-up tilt (HUT) under normovolemic and hypovolemic conditions (randomly), with approximately 4-wk interval. Acute hypovolemia was produced by diuretic (furosemide) administration approximately 2 h before testing. Orthostatic tolerance was determined by progressive lower body negative pressure to presyncope. We found that furosemide produced an approximately 13% reduction in plasma volume, causing a similar increase in supine MSNA in men and women (mean +/- SD of 5 +/- 7 vs. 6 +/- 5 bursts/min; P = 0.895). MSNA increased during HUT and was greater in the hypovolemic than in the normovolemic condition (32 +/- 6 bursts/min in normovolemia vs. 44 +/- 15 bursts/min in hypovolemia in men, P = 0.055; 35 +/- 9 vs. 45 +/- 8 bursts/min in women, P < 0.001); these responses were not different between the genders (gender effect: P = 0.832 and 0.814 in normovolemia and hypovolemia, respectively). Total peripheral resistance increased proportionately with increases in MSNA during HUT; these responses were similar between the genders. However, systolic blood pressure was lower, whereas diastolic blood pressure was similar in women compared with men during HUT, which was associated with a smaller stroke volume or stroke index. Orthostatic tolerance was lower in women, especially under hypovolemic conditions. These results indicate that men and women have comparable sympathetic neural responses during orthostatic stress under normovolemic and hypovolemic conditions. The lower orthostatic tolerance in women is predominantly because of a smaller stroke volume, presumably due to less cardiac filling during orthostasis, especially under hypovolemic conditions, which may overwhelm the vasomotor reserve available for vasoconstriction or precipitate neurally mediated sympathetic withdrawal and syncope.