Perspective: Neuroregenerative Nutrition

Abstract

Good health while aging depends upon optimal cellular and organ functioning that contribute to the regenerative ability of the body during the lifespan, especially when injuries and diseases occur. Although diet may help in the maintenance of cellular fitness during periods of stability or modest decline in the regenerative function of an organ, this approach is inadequate in an aged system, in which the ability to maintain homeostasis is further challenged by aging and the ensuing suboptimal functioning of the regenerative unit, tissue-specific stem cells. Focused nutritional approaches can be used as an intervention to reduce decline in the body's regenerative capacity. This article brings together nutrition-associated therapeutic approaches with the fields of aging, immunology, neurodegenerative disease, and cancer to propose ways in which diet and nutrition can work with standard-of-care and integrated medicine to help improve the brain's function as it ages. The field of regenerative medicine has exploded during the past 2 decades as a result of the discovery of stem cells in nearly every organ system of the body, including the brain, where neural stem cells persist in discrete areas throughout life. This fact, and the uncovering of the genetic basis of plasticity in somatic cells and cancer stem cells, open a door to a world where maintenance and regeneration of organ systems maintain health and extend life expectancy beyond its present limits. An area that has received little attention in regenerative medicine is the influence on regulatory mechanisms and therapeutic potential of nutrition. We propose that a strong relation exists between brain regenerative medicine and nutrition and that nutritional intervention at key times of life could be used to not only maintain optimal functioning of regenerative units as humans age but also play a primary role in therapeutic treatments to combat injury and diseases (in particular, those that occur in the latter one-third of the lifespan).

Keywords: age- and disease-related inflammation; avatar models; combination nutrient therapies; nutrition; regenerative medicine; stem cells.

FIGURE 1

This perspective focuses on a need for more sensitive, reliable, and real-time bioassays for testing personalized and precision diets in which individual nutrient components, along with standard-of-care and integrated medicine practices, can help to treat and prevent degenerative and neoplastic diseases. A focus on stem cells in different growth niches in the brain and body, and the negative consequences on their growth and reparative properties that disease and chronic inflammation have, affords the emerging field of neuroregenerative nutrition to be studied in cell cultures, animal models, and human subjects. The human brain (upper left) contains different populations of indigenous stem and progenitor cells (red and purple cells) that reside in the periventricular subependymal zone along the lateral ventricle and the hippocampus, and has small numbers of stem or progenitor cells within the brain parenchyma (e.g., cerebral cortex) that are amenable to nutrient therapies. These cells also can undergo neoplastic transformation, giving rise to primary brain tumors (green mass in the temporal lobe). The brain stem cell niches interact with parts of the body, including bone marrow and lymph and immune systems (at right, cells in, for example, leg bone marrow and spleen), which is a basis for brain-body-immune system interactions that are compromised during abnormal aging and disease. Stem or progenitor cells that are at risk for both age-related degenerative and neoplastic diseases, along with patient-matched immune cells, can be isolated from these poietic niches and grown together in vitro or following xenotransplantation in host animals to create patient- or disease-specific avatars that are amenable to drug and nutrient testing on a precision medicine level (e.g., a “laboratory on a chip”) with microfluidomic growth and analysis conditions (6) to monitor disease onset, progression, and response to therapies via the interrogation of biomarkers, including exosomes. Chronic inflammation, which often accompanies disease course and treatments, is also a focus of this perspective because of its prevalence in so many disease and tissue injury settings. The use of a combination of omics analyses and computational and systems biology, in particular key regulatory gene and protein pathways, can be predicted to be a nutrient-druggable target, in addition to whole foods that contain these nutritional components as potential preventives and treatments, when higher concentrations of the components are demanded so as to be therapeutic; then they can be combined as polymolecular botanical drug compounds. Micronutrients and probiotics, along with dietary regimens (e.g., low-carbohydrate or ketogenic diet), can be implemented to help deter carbohydrate-enhanced cancer cell growth as well as neural cell loss, as seen in neurodegenerative disorders. Correlating such diet and nutrient administrations with a patient’s unique circadian clock provides critical timing of administration information for both pharmaceutical and dietary choices, which can be important for strategically targeting at-risk cells and tissues.