TY - JOUR
T1 - Early shifts of brain metabolism by caloric restriction preserve white matter integrity and long-term memory in aging mice
AU - Guo, Janet
AU - Bakshi, Vikas
AU - Lin, Ai Ling
N1 - Publisher Copyright:
© 2015 Guo, Bakshi and Lin.
PY - 2015
Y1 - 2015
N2 - Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals' memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions - normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity.
AB - Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals' memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions - normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity.
KW - Brain aging
KW - Caloric restriction
KW - Creatine
KW - Glucose metabolism
KW - Ketone bodies
KW - Long-term memory
KW - Neuroimaging
KW - White matter integrity
UR - http://www.scopus.com/inward/record.url?scp=84949805385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949805385&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2015.00213
DO - 10.3389/fnagi.2015.00213
M3 - Article
AN - SCOPUS:84949805385
VL - 7
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - NOV
M1 - 213
ER -