title: Age-related changes in brain energetics and phospholipid metabolism.
abstract: 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 ((31)P) MRS. (31)P 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 (31)P 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.
authors.affiliation: Geriatric Psychiatry Research Program, McLean Hospital, Belmont, MA, USA. bforester@mclean.harvard.edu
authors.forename: Brent P
authors.initials: BP
authors.lastname: Forester
authors.forename: Yosef A
authors.initials: YA
authors.lastname: Berlow
authors.forename: David G
authors.initials: DG
authors.lastname: Harper
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lange
authors.forename: Michael P
authors.initials: MP
authors.lastname: Froimowitz
authors.forename: Caitlin
authors.initials: C
authors.lastname: Ravichandran
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.forename: Scott E
authors.initials: SE
authors.lastname: Lukas
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism*; D010759:Phosphorus Isotopes; D055815:Young Adult
chemical_list: D010743:Phospholipids; D010759:Phosphorus Isotopes