Altered Brain Mitochondrial Metabolism in Healthy Aging as Assessed by in vivo Magnetic Resonance Spectroscopy

A decline in brain function is a characteristic feature of healthy aging; however, little is known about the biologic basis of this phenomenon. To determine whether there are alterations in brain mitochondrial metabolism associated with healthy aging, we combined 13C/1H magnetic resonance spectroscopy with infusions of [1-13C]glucose and [2-13C]acetate to quantitatively characterize rates of neuronal and astroglial tricarboxylic acid cycles, as well as neuroglial glutamate–glutamine cycling, in healthy elderly and young volunteers. Compared with young subjects, neuronal mitochondrial metabolism and glutamate–glutamine cycle flux was ∼30% lower in elderly subjects. The reduction in individual subjects correlated strongly with reductions in N-acetylaspartate and glutamate concentrations consistent with chronic reductions in brain mitochondrial function. In elderly subjects infused with [2-13C]acetate labeling of glutamine, C4 and C3 differed from that of the young subjects, indicating age-related changes in glial mitochondrial metabolism. Taken together, these studies show that healthy aging is associated with reduced neuronal mitochondrial metabolism and altered glial mitochondrial metabolism, which may in part be responsible for declines in brain function.

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Muscle metabolism in older subjects using 31P magnetic resonance spectroscopy

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-084 ◽

1991 ◽

Vol 69 (5) ◽

pp. 576-580 ◽

Cited By ~ 47

Author(s):

Kevin K. McCully ◽

Mary Ann Forciea ◽

Laurita M. Hack ◽

Eileen Donlon ◽

Roger W. Wheatley ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Time Constant ◽

Plantar Flexion ◽

Muscle Metabolism ◽

The Elderly ◽

Elderly Subjects ◽

Resonance Spectroscopy ◽

Medical Problems ◽

Age Related

We used phosphorus magnetic resonance spectroscopy to study the calf muscles of elderly normal (mean ± SD) (80.0 ± 5.12 years), elderly impaired (80.7 ± 0.58 years), old normal (66.8 ± 1.92 years), and young normal people (24.6 ± 4.72 years). Relative levels of inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate were measured with a 1.9-tesla, 30-cm bore magnet at rest and following plantra flexon exercise. No differences were found at rest or during recovery from exercise in the elderly normal subjects with respect to gender or the presence of stable medical problems treated with medication. At rest there was an age-related decrease in the ratio of PCr/Pi. After exercise, the time constant of PCr recovery increased with age. A mild 7-week exercise regimen consisting of plantar flexion had no effect on time constant of PCr recovery in the elderly subjects. Four elderly impaired subjects had lower PCr/Pi ratios at rest and slower time constant of PCr recovery after exercise than normal elderly subjects. We conclude that gender and the presence of stable medical problems had no effect on muscle metabolism in the elderly and that the elderly recovered slower than young controls. This slower recovery was not corrected with a mild exercise program.Key words: human muscle, aging, exercise, nuclear magnetic resonance, gastrocnemius.

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Faculty Opinions recommendation of Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1819956.2027081 ◽

2010 ◽

Author(s):

Vesna Jevtovic-Todorovic

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Healthy Aging ◽

Mitochondrial Metabolism ◽

Resonance Spectroscopy

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Faculty Opinions recommendation of Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1819956.1357054 ◽

2010 ◽

Author(s):

Kevin Conley

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Healthy Aging ◽

Mitochondrial Metabolism ◽

Resonance Spectroscopy

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Brain Function, Structure, and Neurochemistry after Tamoxifen/Chemotherapy Assessed by Neuropsychologic Testing & H Magnetic Resonance Spectroscopy

PsycEXTRA Dataset ◽

10.1037/e455682006-001 ◽

2001 ◽

Author(s):

Thomas Ernst ◽

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Brain Function ◽

Resonance Spectroscopy ◽

Function Structure ◽

Neuropsychologic Testing

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Brain Function, Structure, and Neurochemistry After Tamoxifen/Chemotherapy Assessed by Neuropsychologic Testing and 1H Magnetic Resonance Spectroscopy

10.21236/ada403373 ◽

2001 ◽

Author(s):

Thomas Ernst

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Brain Function ◽

Resonance Spectroscopy ◽

Function Structure ◽

1H Magnetic Resonance Spectroscopy ◽

Neuropsychologic Testing

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MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy

Cancer Research ◽

10.1158/0008-5472.can-16-2686 ◽

2017 ◽

Vol 77 (21) ◽

pp. 5913-5924 ◽

Cited By ~ 35

Author(s):

Mounia Beloueche-Babari ◽

Slawomir Wantuch ◽

Teresa Casals Galobart ◽

Markella Koniordou ◽

Harold G. Parkes ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Combination Therapy ◽

Mitochondrial Metabolism ◽

Resonance Spectroscopy

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Effect of ‘Autonomic Blockade’ on Cardiac β-Adrenergic Chronotropic Responsiveness in Healthy Young, Healthy Elderly and Endurance-Trained Elderly Subjects

Clinical Science ◽

10.1042/cs0870297 ◽

1994 ◽

Vol 87 (3) ◽

pp. 297-302 ◽

Cited By ~ 15

Author(s):

G. A. Ford ◽

O. F. W. James

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Geometric Mean ◽

Cardiovascular Responses ◽

The Elderly ◽

Elderly Subjects ◽

Healthy Elderly ◽

Age Related ◽

Autonomic Blockade ◽

Young Subjects

1. Cardiac chronotropic responses to isoprenaline are reduced with ageing in man. It is unclear whether this is due to reduced cardiac β-adrenergic sensitivity or to age-associated differences in reflex cardiovascular responses to the vasodilatory effects of isoprenaline. Age-associated changes in physical activity are also reported to influence β-adrenergic sensitivity. 2. The aim of the present study was to determine the contribution of alterations in reflex changes in parasympathetic and sympathetic influences and physical fitness to the age-associated reduction in cardiac chronotropic responses to β-adrenergic agonists. 3. The effect of ‘autonomic blockade’ with atropine (40 μg/kg intravenously) and clonidine (4 μg/kg intravenously) on blood pressure, heart rate and chronotropic responses to intravenous bolus isoprenaline doses was determined in eight healthy young (mean age 21 years), nine healthy elderly (72 years) and 10 endurance-trained elderly (69 years) subjects. 4. Elderly subjects had a reduced increase in heart rate after atropine (young, 49 ± 9 beats/min; elderly, 36 ± 5 beats/min; endurance-trained elderly, 34 ± 12 beats/min; P < 0.01) and did not demonstrate the transient increase in systolic blood pressure after clonidine observed in young subjects (young, 11 ± 10 mmHg; elderly, −12 ± 16 mmHg; endurance-trained elderly, −18 ± 11 mmHg; P < 0.01). 5. Cardiac chronotropic sensitivity to isoprenaline after ‘autonomic blockade’ increased in the young but decreased in the elderly subjects. The isoprenaline dose that increased heart rate by 25 beats/min before and after autonomic blockade' was: young, before 1.6 μg, after 2.8 μg, P < 0.01 (geometric mean, paired test); elderly, before 6.9 μg, after 3.6 μg, P < 0.05; endurance-trained elderly, before 5.9 μg, after 4.0 μg, P < 0.05. Cardiac chronotropic sensitivity to isoprenaline was significantly reduced in elderly compared with young subjects before (P < 0.01) but was similar after (P = 0.09) ‘autonomic blockade’. Chronotropic sensitivity did not differ between healthy and endurance-trained elderly subjects before or after ‘autonomic blockade’. 6. The age-associated reduction in cardiac chronotropic responses to bolus isoprenaline is primarily due to an age-related reduction in the influence of reflex cardiovascular responses on heart rate and not to an age-related reduction in cardiac β-adrenergic sensitivity. Endurance training is not associated with altered β-adrenergic chronotropic sensitivity in the elderly. The transient pressor response to intravenously administered clonidine may be lost in ageing man.

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