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.

Creatine as a booster for human brain function. How might it work?

“…age, including increases in phosphocreatine and ATP [73,82,83] suggesting that total brain bioenergetics capacity increases rather than decreases with age. With increased creatine improving brain function, the reverse has also been shown, where memory exercises have been shown to increase levels of creatine in the hippocampus of healthy elderly performing training in the Method of Loci task, involving delayed recall, spatial and associative memory training, compared to elderly subjects who were merely undertaking tasks of everyday living [84].…”

Extratemporal abnormalities in phosphorus magnetic resonance spectroscopy of patients with mesial temporal sclerosis

“…Other evidence for the role of mitochondrial dysfunction in seizure generation in humans is the increased prevalence of epilepsy with aging. Mitochondrial oxidative stress is a well established mechanism of aging and age-related degenerative disease 27 . Our study is limited by the size of the MRS voxels with contamination from the surrounding structures, especially considering that the number of phase encoding steps was limited by the time of scanning.…”

Avaliação de pacientes com esclerose mesial temporal pela espectroscopia de fósforo por ressonância magnética em aparelho 3T

“…Em relação ao gênero, não há evidências de alterações na 31 P-ERM associadas, já em relação à idade, existem evidências da influência da idade no metabolismo energético e de fosfolipídeos, com alterações significativas em relação a PCr (aumento de 1,1% por década), PME (redução de 1,7% por década) e pH ( redução de 0,53% por década) em indivíduos de 21 a 84 anos de vida (Forester et al, 2010).…”

“…Esta redução funcional na capacidade metabólica poderia levar a disfunções celulares relacionadas ao envelhecimento, como alteração da comunicação e morte celular, que poderiam contribuir para maior prevalência de doenças neurodegenerativas em população senil (Forester et al, 2010 Resultados controversos foram relatados a respeito do pH, sendo que alguns pesquisadores encontraram alcalose no lobo temporal ipsilateral à EMT , Hugg et al, 1992, van der Grond et al, 1998, enquanto outros não encontraram nenhuma diferença (Kuzniecky et al, 1992, Chu et al, 1996.…”

“…Outro indício da importância da mitocôndria na epileptogênese se deve ao aumento da incidência de epilepsia em pacientes mais idosos, provavelmente relacionado à disfunção mitocondrial que ocorre com o envelhecimento (Forester et al, 2010).…”