Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

Parikh, Ishita; Guo, Janet; Chuang, Kai Hsiang; Zhong, Yu; Rempe, Ralf G.; Hoffman, Jared D.; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M.S.; Lin, Ai Ling

doi:10.18632/aging.101094

Cited by 62 publications

(59 citation statements)

References 73 publications

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“…The first test is the EPM. We used EPM to evaluate anxiety of the mice (Bachstetter et al, 2014 ; Parikh et al, 2016 ), which was also performed at Rodent Behavioral Core (RBC) at the UK. The EPM consists of two open and two closed arms elevated 100 cm above the floor.…”

Section: Methodsmentioning

confidence: 99%

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Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

Hoffman

Parikh

Green

et al. 2017

Front. Aging Neurosci.

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Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD.

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Section: Methodsmentioning

confidence: 99%

“…The third test is the RAWM, which is used to measure both spatial working memory and spatial reference memory (Arendash et al, 2001 ; Sood et al, 2007 ; Parikh et al, 2016 ). The RAWM task was conducted in the RBC at the UK as described previously (Guo et al, 2015 ), following a 2-day testing paradigm.…”

Section: Methodsmentioning

confidence: 99%

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

Hoffman

Parikh

Green

et al. 2017

Front. Aging Neurosci.

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“…Such restriction was found to decrease body mass and normalize blood glucose, insulin, and leptin levels in obese animals and humans. In addition to effects on peripheral tissues, DR improves the operation of the central nervous system and weakens symptoms of age-related neurodegenerative disorders in rodent models [1][2][3][4][5][6][7]. There are two different approaches to model DR with rodents.…”

Section: Overweight and Obesity Became The Worldwide Epidemic Resultimentioning

confidence: 99%

Intermittent fasting causes metabolic stress and leucopenia in young mice

Sorochynska¹,

Bayliak²,

Vasylyk³

et al. 2019

Ukr.Biochem.J.

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“…In rodent models, CR leads to beneficial metabolic changes, protection from oxidative stress, neurotrophic factor production, increased autophagy, and neurogenesis 46 – 49 . CR also promotes the maintenance of cerebral blood flow and white matter integrity with age 50 , 51 . While CR has been demonstrated to improve spatial learning and memory in aged mice 51 , global effects on cognition remain unresolved, as CR failed to improve other hippocampal-dependent cognitive processes 52 – 54 .…”

Section: Systemic Interventions: Caloric Restriction Exercise Parabmentioning

confidence: 99%

“…CR also promotes the maintenance of cerebral blood flow and white matter integrity with age 50 , 51 . While CR has been demonstrated to improve spatial learning and memory in aged mice 51 , global effects on cognition remain unresolved, as CR failed to improve other hippocampal-dependent cognitive processes 52 – 54 . It is suggested that such inconsistent results could be due to the varied macronutrient ratios in CR regimes, the age of CR onset, and the metabolic heterogeneity of the diverse cell types in the hippocampus 55 – 57 .…”

Section: Systemic Interventions: Caloric Restriction Exercise Parabmentioning

confidence: 99%

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

Horowitz

Villeda

2017

F1000Res

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Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

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Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

Cited by 62 publications

References 73 publications

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

Intermittent fasting causes metabolic stress and leucopenia in young mice

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

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