How vitamins and minerals may prevent age-related diseases

ScienceDaily (June 1, 2011) — Severe deficiency of the vitamins and minerals required for life is relatively uncommon in developed nations, but modest deficiency is very common and often not taken seriously. A new research published online in the FASEB Journal, however, may change this thinking as it examines moderate selenium and vitamin K deficiency to show how damage accumulates over time as a result of vitamin and mineral loss, leading to age-related diseases.

See Also:Health & MedicineDietary SupplementVitaminVitamin AVitamin EVitamin BHealthy AgingLiving WellReferenceMicronutrientDietary mineralEssential nutrientVitamin K

"Understanding how best to define and measure optimum nutrition will make the application of new technologies to allow each person to optimize their own nutrition a much more realistic possibility than it is today." said Joyce C. McCann, Ph.D., a co-author of the study from the Nutrition and Metabolism Center at Children's Hospital Oakland Research Institute in Oakland, California. "If the principles of the theory, as demonstrated for vitamin K and selenium, can be generalized to other vitamins and minerals, this may provide the foundation needed."

McCann and colleagues reached their conclusions by compiling and assessing several general types of scientific evidence. They tested whether selenium-dependent proteins that are essential from an evolutionary perspective are more resistant to selenium deficiency than those that are less essential. They discovered a highly sophisticated array of mechanisms at cellular and tissue levels that, when selenium is limited, protect essential selenium-dependent proteins at the expense of those that are nonessential. They also found that mutations in selenium-dependent proteins that are lost on modest selenium deficiency result in characteristics shared by age-related diseases including cancer, heart disease, and loss of immune or brain function. Results should inform attempts to locate mechanistic linkages between vitamin or mineral deficiencies and age-related diseases by focusing attention on the vitamin and mineral-dependent proteins that are nonessential from an evolutionary perspective. Such mechanistic linkages are likely to present opportunities for treatment.

"This paper should settle any debate about the importance of taking a good, complete, multivitamin every day," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "As this report shows, taking a multivitamin that contains selenium is a good way to prevent deficiencies that, over time, can cause harm in ways that we are just beginning to understand."

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Hormone precursor inhibits brain inflammation: Molecule moderates condition linked to neurodegenerative diseases

ScienceDaily (May 15, 2011) — Researchers at the University of California, San Diego School of Medicine have discovered a steroid hormone that inhibits inflammation in the brain. The findings, to be published in the May 13 issue of the journal Cell, have implications for understanding the exaggerated inflammatory responses that are characteristic features of numerous neurodegenerative diseases.

See Also:Health & MedicineImmune SystemCrohn's DiseaseHormone DisordersMind & BrainDisorders and SyndromesAlzheimer'sParkinson'sReferenceMyelinInflammationNatural killer cellAstrocyte

The discovery that the steroid hormone ADIOL, (5-androsten-3Β-17Β-diol), a precursor of androgens and estrogens, modulates inflammation induced by microglia cells could eventually lead to new treatments for patients with neurodegenerative conditions in which inflammation plays a pathogenic role. In addition, levels of ADIOL in blood or other body fluids might be useful for predicting risk or responses to drugs that mimic its actions.

The senior author of the paper is Christopher Glass, MD, PhD, professor of the department of cellular and molecular medicine and the department of medicine. Lead author is Kaoru Saijo, MD, PhD, and an associate project scientist in the Glass lab.

Though neurons get the headlines, they thrive only with the support of other cell types, among them microglia and astrocyte cells. Microglial cells help the central nervous system respond to infection and injury. Under normal conditions, they exist in a resting state, quietly but constantly surveying their surrounding environment for tell-tale indications of microbial invasion or tissue damage. Once detected, microglia initiate an inflammatory response, kick-starting immune system and tissue repair processes. Astrocytes amplify the immune reaction launched by microglia.

The microglia-astrocyte activation is vital to an effective immune response and damage repair, but if the resulting inflammation induced by these cells is not controlled or goes on too long, it can result in damage and death to neurons. Inflammation run amok is linked to many neurodegenerative diseases, such as Parkinson's disease, HIV-associated dementia, Alzheimer's disease and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and some inflammatory diseases like multiple sclerosis (MS).

The new findings suggest that in healthy brains, microglia inflammation is modulated by the production of the steroid hormone ADIOL, which instructs support cells to calm down and return to their quiescent state. ADIOL works by binding to a transcription factor called estrogen receptor Β, which gets its name because of its similarity to estrogen receptor Β and its ability to bind to the female sex hormone estrogen. Unexpectedly, while ADIOL binding causes estrogen receptor α to execute an anti-inflammatory set of instructions to microglia and astrocytes, estrogen binding does not. Because of this, estrogens can actually antagonize the anti-inflammatory actions of ADIOL.

Glass and Saijo made their discovery based upon initial studies with John Katzenellenbogen, PhD, at the University of Illinois, Urbana-Champaign. Kaztenellenbogen's laboratory developed a number of synthetic small molecules that could bind very tightly and specifically to estrogen receptor .

Saijo at UC San Diego tested each of these compounds and found that some were potent inhibitors of inflammatory responses of microglia and astrocytes, while others were not. When one of these compounds was tested in vivo, it was found to strongly inhibit inflammation in the brain and to induce remission in a mouse model of multiple sclerosis.

Although estrogen itself can be neuroprotective, its lack of ability to induce the anti-inflammatory activity of estrogen receptor  led to a search for endogenous or internal molecules that might have similar activities to the synthetic compounds. Saijo worked with Andrew Li, MD, assistant adjunct professor of medicine at UC San Diego, to ultimately identify ADIOL as the endogenous regulator of estrogen receptor  activity. Notably, Saijo and Li found that the amount of ADIOL that could be produced by microglia was regulated by signals that control the magnitude and duration of inflammatory responses

"We think it possible that mutations in the genes encoding the key enzymes for the generation of ADIOL, or their inappropriate down-regulation, could contribute to pathological forms of inflammation," Glass said.

These findings raise the possibility that women are more susceptible to certain inflammatory diseases, such as MS, because their higher levels of estrogens potentially antagonize the anti-inflammatory actions of ADIOL in the brain. A similar argument might also help explain some of the adverse effects of estrogen administration on the brain in post-menopausal women.

Glass noted, however, that much research remains to be done. The precise relationship between brain inflammation and neurodegenerative disease, for example, is not fully understood. Similarly, it's not known whether people naturally produce different amounts of ADIOL. And researchers have only identified the ADIOL-estrogen connection in an MS mouse model. Glass said he and colleagues will next look at animal models for Alzheimer's, Parkinson's and HIV-dementia.

Co-authors of the study include Jana G. Collier, UCSD Department of Cellular and Molecular Medicine.

Funding for this study was provided by the National Institutes of Health.

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