Age-related changes in brain energetics and phospholipid metabolism

• Published in: NMR in biomedicine 2010-04, Vol.23 (3), p.242-250
• Main Authors: Forester, Brent P., Berlow, Yosef A., Harper, David G., Jensen, J. Eric, Lange, Nicholas, Froimowitz, Michael P., Ravichandran, Caitlin, Iosifescu, Dan V., Lukas, Scott E., Renshaw, Perry F., Cohen, Bruce M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; aging; Aging - metabolism; Brain - metabolism; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Linear Models; Magnetic Resonance Spectroscopy; Male; Middle Aged; mitochondria; Phospholipids - metabolism; Phosphorus Isotopes; TAP utilization; Young Adult
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.1444

Evidence suggests that mitochondria undergo functional and morphological changes with age. This study aimed to investigate the relationship of brain energy metabolism to healthy aging by assessing tissue specific differences in metabolites observable by phosphorus (31P) MRS. 31P MRSI at 4 Tesla (T) was performed on 34 volunteers, aged 21–84, screened to exclude serious medical and psychiatric diagnoses. Linear mixed effects models were used to analyze the effects of age on phosphorus metabolite concentrations, intracellular magnesium and pH estimates in brain tissue. A significant age associated decrease in brain pH (−0.53% per decade), increase in PCr (1.1% per decade) and decrease in PME (1.7% per decade) were found in total tissue, with PCr effects localized to the gray matter. An increase in beta NTP as a function of age (1% per decade) approached significance (p = 0.052). There were no effects demonstrated with increasing age for intracellular magnesium, PDE or inorganic phosphate. This study reports the effects of healthy aging on brain chemistry in the gray matter versus white matter using 31P MRS measures of high energy phosphates, pH and membrane metabolism. Increased PCr, increased beta NTP (reflecting ATP) and reduced pH may reflect altered energy production with healthy aging. Unlike some previous studies of aging and brain chemistry, this study examined healthy, non‐demented and psychiatrically stable older adults and specifically analyzed gray‐white matter differences in brain metabolism. Copyright © 2009 John Wiley & Sons, Ltd. This study utilized 31P MRSI at 4 Tesla (T) on 34 volunteers, aged 21—84, to investigate the relationship of brain energy metabolism to healthy aging by assessing tissue specific differences in brain metabolites. Linear mixed effects models demonstrated a significant age associated decrease in brain pH (0.53% per decade), increase in PCr (1.1% per decade) and decrease in PME (1.7% per decade) in total tissue, with PCr effects localized to the gray matter. An increase in beta NTP as a function of age (1% per decade) approached significance (p = 0.052).