Aging, Physical Activity and Blood Flow

quadriceps muscle anatomy

Physical activity diminishes age's affect on the reduction of the potent vasodilator NO. Elevated NO in the blood results from or causes a reduction in the amount of dangerous radical oxygen species in the blood.

Many physiology studies have shown that reactive oxygen species increase in humans with age. Reactive oxygen species have been impacted in the age-related deterioration of the brain. Fortunately, physical activity has been shown to decrease the concentration of reactive oxygen species. The role that physical activity has on preventing Alzheimer's Disease through reactive oxygen species reduction was discussed in a previous post on The focus here is the effect that physical activity has on the concentration of reactive oxygen species in the skeletal muscle.

Nitric oxide (NO) is a key regulator of vasodilation in blood vessels feeding the skeletal muscles. When reactive oxygen species are present, nitric oxide gets catabolized. One of the reasons antioxidants are so popular in the health food industry is because, as their name suggests, antioxidants eliminate reactive oxygen species. Older sedentary humans should show the greatest increase in NO following treatment with antioxidants because antioxidants are more prevalent in older patients who abstain from physical activity. One recent Danish study tested this hypothesis by treating subjects with the antioxidant N-acetylcysteine (Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans, 2012.  Michael Nyberg, et al.).

The study placed 8 subjects into each group: a sedentary youth group (mean age: 23), a sedentary older group (mean age: 66) and a physically active older group (mean age: 62). The subjects performed knee extensions for the exercise variable. The study found that the sedentary youth group had the highest concentration of NO metabolites, NOx. The physically active older group, although lower than the youth group, had a higher concentration of NOx in muscle tissue than the sedentary older group. When the older sedentary group was provided with antioxidant N-acetylcysteine (NAC) their NOx levels rose to the active older group with out antioxidants (Control, CON). Both older groups saw a significant increase in NOx concentration, suggesting that NO was compromised by radical oxygen species. At 45% of maximum power output only the older sedentary group saw increases in muscle interstitial NOx concentration following injection of antioxidant NAC. The results can be seen in the figure below.

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Figure 1. Muscle interstitial NOx at rest and during 12 W and 45% Wmax without and with infusion of NAC
Exercise was performed at the same absolute workload of 12 watts and at a relative workload corresponding to 45% Wmax without (CON) or with (NAC) infusion of N-acetylcysteine in young sedentary, older sedentary and older active subjects.  †Significantly different from young sedentary within same condition, P < 0.05; ∗significantly different from control conditions,  P < 0.05; #significantly different from rest within same condition, P < 0.05. 

The older active group showed no decrease in NO2 in their arteries when treated with antioxidant NAC. The young and old sedentary groups both saw increases in arterial NO2 (as shown in the figure below only the older sedentary group saw a significant increase in arterial NO2). This means that only the older active group was able to contain the radical oxygen species.  

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Figure 2. Plasma NO2− and NOx at rest without and with infusion of NAC
Femoral arterial blood samples collected during rest without (CON) or with (NAC) infusion of N-acetylcysteine in young sedentary, older sedentary and older active subjects. ∗Significantly different from control conditions, P<0.05 

Although antioxidants increased the amount of NO in the blood, the blood flow to the legs did not increase following antioxidant administration. The increase in NO concentration did not cause an increase in leg muscle blood flow. This result is surprising because NO is known to be a potent vasodilator. Thus, exercise-induced hyperemia (increased blood flow) must occur through a pathway other than NO in the legs.

Figure 3. Leg haemodynamics at rest and during 12 W and 45% Wmax
Exercise and rest without (CON) or with (NAC) antioxidant in young sedentary, older sedentary and older active subjects. †Significantly different from young sedentary within same condition; #significantly different from rest, ‡significantly different from older sedentary within same condition.

This study showed that one mechanism by which NO is increased in physically active elders is through a decrease in radical oxygen species. Another mechanism is an increase in Nitric Oxide Synthase (NOS), a protein that synthesizes NO. The physically active older subjects were found to have a significantly higher amount of endothelial NOS and neural NOS. The authors suggest that the elevated amount of NOS in active older subjects could act as a radical oxygen species scavenger. The increase in NO production may compensate for the age-related increase in radical oxygen species.

In conclusion, the discussed study found that physical activity decreased age's affect on nitric oxide (NO) decline in the blood. NO is a vasodilator, it opens up blood vessels. The concentration of radical oxygen species was lower in the physically active older subjects than the sedentary older active subjects. The older active subjects had the highest amount of nitric oxide synthase (NOS).  Since radical oxygen species decrease NO concentration, NO concentration may be elevated in the physically active because the combined effects of lower radical oxygen species and higher NOS. Another possibility is that NO scavenges radical oxygen species. This means that the low concentration of radical oxygen species is the product, rather than the cause, of high NO levels in the blood. In addition, nitric oxide was found to play no role in hyperemia during physical activity. Regardless, physical activity is important for maintaining vascular health by maintaining nitric oxide levels with aging.

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