The effects of aging and activity on muscle blood flow
© Olive et al; licensee BioMed Central Ltd. 2002
Received: 9 November 2002
Accepted: 19 December 2002
Published: 19 December 2002
Our purpose was to determine if aging had an influence on muscle blood flow independent of habitual physical activity levels.
Blood flow was measured in the femoral artery by Doppler ultrasound after cuff occlusion of 10 minutes. Active and inactive older subjects (73 ± 7 years) were compared to active and inactive young subjects (26 ± 6 years).
Peak blood flow capacity when normalized to lean muscle mass was related to activity level (p < 0.001), but not to age. Specifically, the young active group had higher peak blood flows than the young inactive (p = 0.031) or older inactive (p = 0.005) groups. Resting blood flow and conductance were not significantly different between groups. Mean arterial pressure was significantly higher in the older compared to young group (p = 0.002). Conductance was related to both activity (p = 0.002) and age (p = 0.003). A prolonged time for blood flow to recover was found in the older compared to the young group (p = 0.038) independent of activity status.
The prolonged recovery time in the older subjects may suggest a reduced vascular reactivity associated with increased cardiovascular disease risk. Peak blood flow capacity is maintained in older subjects by physical activity. In summary, maximal flow capacity and prolonged recovery of blood flow are influenced by different mechanisms in young and older active and inactive subjects.
KeywordsBlood flow Aging Doppler ultrasound Perfusion Skeletal Muscle
Aging has been associated with decreased function and exercise performance [1, 2]. Decreased exercise performance has been related to decreased oxidative capacity [3, 4] and decreased muscle mass . Vascular alterations in structure and function due to aging could also contribute to decreased exercise performance through impaired blood flow . Decreased capillary density  and a thickening of vascular walls  are present with aging.
Vascular function is altered with aging and may influence muscle blood flow and exercise performance. Altered vascular function in older individuals is evidenced as impaired endothelial function [8–10], an altered ratio of endothelin receptors , and/or altered reactivity of the smooth muscle to sympathetic activity [7, 12]. Reduced endothelial function is related to impaired formation and decreased activation of nitric oxide [13, 14] and is particularly prominent in older subjects with evidence of cardiovascular disease , diabetes , or obesity . Interestingly, aging does not appear to effect endothelium independent vasodilation [10, 14].
These structural and functional alterations in the vascular system may explain age associated reductions in muscle blood flow. Decreased leg blood flow and vascular conductance are present in elderly compared to young subjects during whole body exercise  and in response to reactive hyperemia . Decreased basal limb blood flow was related to increased vasoconstriction in the elderly compared to younger individuals . However, not all studies have shown age related changes in blood flow. Resting blood flow and post exercise hyperemia was similar in elderly compared to younger subjects . Blood flow responses to single limb exercise have also been preserved in older individuals [21, 22]. Discrepancies in aging effects on muscle blood flow may be due to the use of active  or inactive subjects . In addition, it is not clear whether the age related changes in blood flow were a result of reduced cardiac output during whole body exercise or reduced local vascular capacity. These inconsistent findings of reduced blood flow in older subjects suggest that other age-associated factors are involved.
Physical activity status influences vascular function and may explain alterations in muscle blood flow. Exercise training increases cardiac output during exercise and increases skeletal muscle blood flow in response to reactive hyperemia . Arterial diameters [19, 24], capillary density [5, 25], vascular reactivity [26, 27], and endothelial function [9, 28] are improved with training and reduced with inactivity.
The purpose of this study was to determine if aging had an influence on muscle blood flow independent of habitual physical activity levels. Specifically, we examined single leg blood flow in response to reactive hyperemia with active and inactive older subjects in comparison to active and inactive young subjects. We tested the hypothesis that aging would result in reductions in limb blood flow independent of physical activity.
Subject Characteristics – Means (SD)
Differences by Group
Gender (Male: Female)
BP Systolic/Diastolic (mmHg)
Mean Arterial Pressure
Heart Rate (BPM)
Lean Leg Vol. (cm3)
Subjects rested in a supine position for 10–15 minutes prior to testing. Resting blood pressure was obtained. Ischemia was induced in the lower limb by inflation of a blood pressure cuff 100 mmHg above systolic blood pressure measured in the arm. Blood flow was measured at rest and in response to 10 minutes of cuff ischemia. Cuff placement was distal to the Doppler probe and was placed directly above the knee. Cuff inflation and deflation was rapid (1–2 seconds) using a rapid inflation device (D.E. Hokanson, Inc). Blood pressure was measured continuously to measure changes during the test as a result of cuff ischemia (Finapres, Ohmeda).
Blood flow was measured continuously in the common femoral artery using quantitative Doppler ultrasound (General Electric LogiQ 400 CL) with a frequency of 6 MHz. Pulsed Doppler ultrasound was recorded using an insonation angle of 45°-60°. The velocity gate was set to include the entire arterial diameter. Doppler waveforms were analyzed to determine the time average maximum velocity by General Electric's advanced vascular program software. B-mode images were measured during diastole to determine vessel diameter. Peak systolic blood flow was calculated as the product of the vessel cross sectional area and time average maximal velocity. Blood flow response to 10 minutes of cuff ischemia was an index of peak blood flow response . Conductance was calculated by dividing the maximal blood flow by the mean arterial pressure (MAP). Half time to recovery was determined as the time where blood flow dropped to one half the magnitudes between maximum flow and resting flow values.
Near Infrared Spectroscopy (NIRS)
Muscle oxygen delivery was determined by the half time of recovery of oxygen saturation after cuff ischemia. Oxygen saturation was measured using a continuous light source, dual wavelength NIRS device (Runman CW2000, NIM, Inc., Philadelphia). The probe contained two small tungsten filament lamps, 6 cm apart which emit white light, and two photo detectors with filters for 760 and 850 nm light located between the lights. Brief flashes of light migrated through the tissue and were collected by the detectors at wavelengths set by two optical filters. Oxyhemoglobin has a greater absorbance at 850 nm compared to 760 nm, with deoxyhemoglobin absorbing more at 760 than 850 nm. The difference between the signal at 760 and 850 nm was used as the index of relative oxygen saturation.
Leg volume measurements were determined by Doppler ultrasound measurements of fat thickness and by circumference measurements of the lower leg. Subcutaneous fat was determined by B-mode images of the thickness between skin and muscle fascia. Measurements were attained every three centimeters over the Medial Gastrocnemius and over the Anterior Tibialis muscles. Based on the circumference and fat measurements total leg, fat, and lean area volume, were calculated.
An analysis of variance (ANOVA) (SPSS version 10.0) was conducted to test for aging and activity effects as well as to test for differences by group. Data was analyzed to verify normality and to test for any outliers. Analyses were conducted at a significance level of 0.05.
Flow data and half time to recovery data for groups – Means (SD)
Normalized Resting Blood Flow (ml/100 g/min)
Resting Conductance (ml/100 g/min/mmHg)
Normalized Maximal Blood Flow (ml/100 g/min)
Maximal Conductance (ml/100 g/min/mmHg)
Half Time to Recovery of Blood Flow (seconds)
Half Time to Recovery of NIRS (seconds)
The cuff occlusion protocol was not associated with any changes in heart rate or blood pressure. There was a greater time averaged maximal blood flow in the younger groups (2180 ± 590 ml/min vs. 1700 ± 570 ml/min, for young versus older, respectively; F(1,35) = 5.986, p = 0.020, Η2 = 0.154) and active groups (2220 ± 640 ml/min versus 1680 ± 470 ml/min, for active versus inactive, respectively; F(1,35) = 8.015, p = 0.008, Η2 = 0.195). The maximal blood flow was different between groups (F(3,35) = 5.764, p = 0.003, Η2 = 0.358) with the young active group having higher blood flow than the young inactive group (p = 0.047) and the old inactive group (p = 0.002) (Table 2).
The purpose of this study was to determine if aging or activity had an effect on peripheral blood flow. The primary finding of this study was that peak blood flow capacity was related to activity level while there was no age effect independent of activity level. Our results are consistent with others which have reported no age-related changes in maximal flow capacity after exercise [20–22]. A strength of this study was that maximal blood flow capacity was normalized to estimated lean muscle mass, to correct for age-related decreases in muscle mass .
We did not find age related changes in resting blood flow or resting diameter. In contrast, other studies have found age-related changes in resting blood flow which have been attributed to increases in sympathetic tone [19, 30]. Aging has been associated with reduced blood flow and vascular conductance during whole body exercise . The reduction in blood flow and conductance have been related to alterations in cardiac output and blood volume due to aging . Several of our resting blood flow variables approached significance (p values below 0.10) indicating that our results may have been significant with a larger sample size. However, the significance of age related changes in resting blood flow are unclear other than serving as a marker for altered sympathetic tone; especially if maximal blood flow capacity is not changed with age.
We found that our active subjects had greater maximal blood flow capacity (≈ 30%) than our inactive subjects regardless of age. Consistent with our results Martin et al.  reported a greater vasodilatory capacity in trained than untrained subjects independent of age. Inactivity has been associated with impaired efficiency of peripheral oxygen extraction  and reduced blood flow after cuff ischemia . Conversely, exercise training results in greater maximal flow capacity [31, 34]. Regular aerobic exercise also prevents the age-associated loss in endothelium dependent vasodilation maintaining maximal flow capacity . Our findings support previous research that maximal flow capacity is maintained by aerobic exercise and is independent of age.
Because blood flow is dependent on perfusion pressure, blood flow data is often presented as conductance (flow divided by mean arterial pressure). This is important in aging studies as age is associated with increases in blood pressure [19, 30]. We found that maximal conductance was reduced in our older subjects, consistent with a higher mean arterial pressure in these subjects. We also found higher maximal conductance in the young active group compared to the older inactive subjects, again explained by differences in mean arterial pressure. Another study has reported aging to be associated with reduced conductance . However, it is unclear how important differences in maximal conductance between groups is when there is no difference in maximal blood flow. The lack of difference in blood flow suggests that oxygen delivery is not compromised despite the reduced conductance. It is possible that the vascular system in the older subjects has compensated for the higher mean arterial pressures.
Consistent with the lack of age differences in maximal blood flow, we found no age differences in oxygen delivery as measured by NIRS. Oxygen delivery after exercise has been found to be similar between healthy active older and younger subjects . It was expected, however, that oxygen delivery would be different between the active and inactive individuals. The older inactive did appear to have prolonged oxygen delivery but the young inactive did not. This suggests that oxygen delivery may be more sensitive to the interaction of age and inactivity. Future studies are needed to clarify the influence of age and activity level on oxygen delivery.
An interesting finding in this study was that the half time to recovery of blood flow was prolonged (≈ 28%) in the older compared to young subjects, independent of activity status. This is one of the first studies to our knowledge that has investigated blood flow recovery kinetics in these populations. Slow recovery of blood flow has been used as an index of reduced vascular reactivity in coronary arteries . The hyperemic response to ischemia is dependent on the presence and response to metabolic factors and vasoactive substances such as nitric oxide and adenosine . The prolonged recovery of blood flow in our study could be due to either a greater buildup of metabolic factors/vasoactive substances and/or a diminished ability to remove them in the older subjects. This study, however, was not designed to determine the mechanism for the increased time for blood flow to recover. A prolonged half time to recovery has been associated with a decreased nitric oxide and prostanoid production  and a loss of endothelium dependent vasodilation . Reduced vascular reactivity is associated with many diseases that are associated with aging [15–17]. We did not find activity effects on half time to recovery. This finding contrasts other previously published studies which have shown decreased vascular reactivity in individuals who are required to be on bed rest [26, 38] and in individuals with spinal cord injuries . It is possible that the differences in activity levels between our groups in this study were not large enough to produce the same effects that are seen with bed rest and spinal cord injury.
In summary, we found that maximal blood flow capacity was significantly related to activity level but was not related to age. Blood flow calculated as conductance was related to aging and activity, consistent with the reduced blood flow in the inactive subjects and the higher blood pressures in the older subjects. In addition, the older subjects had evidence of reduced vascular reactivity, as measured by prolonged half time to recovery, independent of activity status. The prolonged half time to recovery in the older subjects is likely related to a reduced vascular reactivity associated with increased cardiovascular disease risk. Thus, maximal flow capacity and the half time to recovery of blood flow are influenced by different mechanisms in young and older active and inactive subjects.
Financial support provided by NIH grant HL65179.
- Astrand I, Astrand P, Hallback I: Reduction in maximal oxygen uptake with age. J Appl Physiol. 1973, 35: 649-655.PubMedGoogle Scholar
- Flegg J, Lakatta E: Role of muscle loss in the age-associated reduction in VO2max. J Appl Physiol. 1988, 65: 1147-1151.Google Scholar
- McCully K, Forciea M, Hack L, Donlon E, Wheatley R, Oatis C, Goldberg T, Chance B: Muscle metabolism in older subjects using 31P magnetic resonance spectroscopy. Can J Physiol Pharmacol. 1991, 69: 576-580.PubMedView ArticleGoogle Scholar
- Conley K, Esselman P, Jubrias S, Cress M, Inglin B, Mogadam C, Schoene R: Ageing, muscle properties and maximal O2 uptake rate in humans. J Physiol (Lond). 2000, 526.1: 211-217.View ArticleGoogle Scholar
- Borisov AB, Huang SK, Carlson BM: Remodeling of the vascular bed and progressive loss of capillaries in denervated skeletal muscle. The Anatomical Record. 2000, 258: 292-304. 10.1002/(SICI)1097-0185(20000301)258:3<292::AID-AR9>3.0.CO;2-N.PubMedView ArticleGoogle Scholar
- Coggan A, Spina R, King D, Rogers M, Brown M, Nemeth P, Holloszy J: Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. J Gerontology. 1992, 47: B71-76.View ArticleGoogle Scholar
- Moreau P, d'Uscio L, Luscher T: Structure and reactivity of small arteries in aging. Cardiovasc Res. 1998, 37: 247-253. 10.1016/S0008-6363(97)00225-3.PubMedView ArticleGoogle Scholar
- Singh N, Prasad S, Singer DRJ, MacAllister RJ: Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm. Clin Sci. 2002, 102: 595-600. 10.1042/CS20010262.PubMedView ArticleGoogle Scholar
- DeSouza CA, Shapiro LF, Clevenger CM, Dinenno FA, Monahan KD, Tanaka H, Seals DR: Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation. 2000, 102: 1351-1357.PubMedView ArticleGoogle Scholar
- Gerhard M, Roddy M, Creager S, Creager M: Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension. 1996, 27: 849-853.PubMedView ArticleGoogle Scholar
- Ergul A, Shoemaker K, Puett D, Tackett R: Gender differences in the expression of endothelin receptors in human saphenous veins in vitro. J Pharmacol Exp Ther. 1998, 285: 511-517.PubMedGoogle Scholar
- Hausberg M, Hoffman R, Somers V, Sinkey C, Mark A, Anderson E: Contrasting autonomic and hemodynamic effects of insulin in healthy elderly versus young subjects. Hypertension. 1997, 29: 700-705.PubMedView ArticleGoogle Scholar
- Sarabi M, Millgard J, Lind L: Effects of age, gender and metabolic factors on endothelium-dependent vasodilation: a population-based study. J Intern Med. 1999, 246: 265-274. 10.1046/j.1365-2796.1999.00542.x.PubMedView ArticleGoogle Scholar
- Kvernmo H, Stefanovska , Kirkeboen K, Osterud B, Kvernebo K: Enhanced endothelium-dependent vasodilation in human skin vasculature induced by physical conditioning. Eur J Appl Physiol. 1998, 79: 30-36. 10.1007/s004210050469.View ArticleGoogle Scholar
- Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I, et al: Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992, 340: 1111-1115. 10.1016/0140-6736(92)93147-F.PubMedView ArticleGoogle Scholar
- Williams S, Cusco J, Roddy M, Johnstone M, Creager M: Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1996, 27: 567-574. 10.1016/0735-1097(95)00522-6.PubMedView ArticleGoogle Scholar
- Steinberg H, Chaker H, Leaming R, Johnson A, Brechtel G, Baron A: Obesity/insulin resistance is associated with endothelial dysfunction. J Clin Invest. 1996, 97: 2601-2610.PubMedPubMed CentralView ArticleGoogle Scholar
- Proctor D, Shen P, Dietz N, Eickhoff T, Lawler L, Ebersold E, Loeffler D, Joyner M: Reduced leg blood flow during dynamic exercise in older endurance-trained men. J Appl Physiol. 1998, 85: 68-75.PubMedGoogle Scholar
- Dinenno FA, Seals DR, DeSouza CA, Tanaka H: Age-related decreases in basal limb blood flow in humans: time course, determinants and habitual exercise effects. J Physiol (Lond). 2001, 531: 573-579.View ArticleGoogle Scholar
- Richardson D, Shewchuk R: Comparison of calf muscle blood flow responses to rhythmic exercise between mean age 25- and 74-year-old men. Proc Soc Exp Biol Med. 1980, 164: 550-555.PubMedView ArticleGoogle Scholar
- Magnusson G, Kaijser L, Isberg B, Saltin B: Cardiovascular responses during one- and two-legged exercise in middle-aged men. Acta Physiol Scand. 1994, 150: 353-362.PubMedView ArticleGoogle Scholar
- Jasperse J, Seals D, Callister R: Active forearm blood flow adjustments to handgrip exercise in young and older healthy men. J Physiol (Lond). 1994, 474: 353-360.View ArticleGoogle Scholar
- Wilmore J, Stanforth P, Gagon J, Rice T, Mandel S, Leon A, Rao D, Skinner J, Bouchard C: Cardiac output and stroke volume changes with endurance training: the HERITAGE family study. Med Sci Sports Exerc. 2001, 33: 99-106. 10.1097/00005768-200101000-00016.PubMedView ArticleGoogle Scholar
- Gerrits H, de Haan A, Sargeant A, van Langen H, Hopman M: Peripheral vascular changes after electrically stimulated cycle training in people with spinal cord injury. Arch Phys Med Rehabil. 2001, 82: 832-839. 10.1053/apmr.2001.23305.PubMedView ArticleGoogle Scholar
- Tyml K, Mathieu-Costello O, Noble E: Microvascular response to ischemia, and endothelial ultrastructure, in disused skeletal muscle. Microvasc Res. 1995, 49: 17-32. 10.1006/mvre.1995.1003.PubMedView ArticleGoogle Scholar
- Shoemaker JK, Hogeman CS, Silber DH, Gray K, Herr M, Sinoway LI: Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses. J Appl Physiol. 1998, 84: 1756-1762.PubMedGoogle Scholar
- Olive JL, McCully KK, Dudley GA: Blood flow response in individuals with incomplete spinal cord injuries. Spinal Cord.Google Scholar
- Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, Jubb M, World M, Deanfield JE: Exercise training enhances endothelial function in young men. J Am Coll Cardiol. 1999, 33: 1379-1385. 10.1016/S0735-1097(99)00036-4.PubMedView ArticleGoogle Scholar
- McCully K, Natelson B: Impaired oxygen delivery in chronic fatigue syndrome. Clin Sci. 1999, 97: 603-608. 10.1042/CS19980372.PubMedView ArticleGoogle Scholar
- Dinenno FA, Jones PP, Seals DR, Tanaka H: Limb Blood Flow and Vascular Conductance Are Reduced With Age in Healthy Humans : Relation to Elevations in Sympathetic Nerve Activity and Declines in Oxygen Demand. Circulation. 1999, 100: 164-170.PubMedView ArticleGoogle Scholar
- Martin W, Ogawa T, Kohrt M, Korte E, Kieffer P, Schechtman K: Effects of aging, gender, and physical training on peripheral vascular function. Circulation. 1991, 84: 654-664.PubMedView ArticleGoogle Scholar
- McGuire DK, Levine BD, Williamson JW, Snell PG, Blomqvist CG, Saltin B, Mitchell JH: A 30-Year Follow-Up of the Dallas Bed Rest and Training Study: I. Effect of Age on the Cardiovascular Response to Exercise. Circulation. 2001, 104: 1350-1357.PubMedView ArticleGoogle Scholar
- Kroese A: The effect of inactivity on reactive hyperaemia in the human calf: a study with strain gauge plethysmography. Scand J Clin Lab Invest. 1977, 37: 53-58.PubMedView ArticleGoogle Scholar
- Snell P, Martin W, Buckey J, Blomqvist C: Maximal vascular leg conductance in trained and untrained men. J Appl Physiol. 1987, 62: 606-610.PubMedGoogle Scholar
- McCully K, Halber C, Posner J: Exercise-induced changes in oxygen saturation in the calf muscles of elderly subjects with peripheral vascular disease. J Gerontol. 1994, 49: B128-B134.PubMedView ArticleGoogle Scholar
- Parker J, Oltman C, Muller J, Myers P, Adams H, Laughlin MH: Effects of exercise training on regulation of tone in coronary arteries and arterioles. Med Sci Sports Exerc. 1994, 26: 1252-1261.PubMedView ArticleGoogle Scholar
- Shoemaker JK, Halliwill JR, Hughson RL, Joyner MJ: Contributions of acetylcholine and nitric oxide to forearm blood flow at exercise onset and recovery. Am J Physiol Heart Circ Physiol. 1997, 273: H2388-2395.Google Scholar
- Kamiya A, Iwase S, Michikami D, Fu Q, Mano T: Head-down bed rest alters sympathetic and cardiovascular responses to mental stress. Am J Physiol Regulatory Integrative Comp Physiol. 2000, 279: R440-R447.Google Scholar
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