MedicalResearch.com Interview with:
Ashok K. Shetty, Ph.D.
Professor and Director of Neurosciences
Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine
Texas A&M Health Science Center College of Medicine, Temple, TX
Research Career Scientist, Central Texas Veterans Health Care System (CTVHCS), Temple, TX
Medical Research: What is the background for this study?
Prof. Shetty: Hippocampus is a region in the brain important for maintaining functions such as learning, memory and mood. However, this region is highly vulnerable to aging and brain insults. Previous research has shown that diminished function in the dentate gyrus region of the hippocampus is one of the key reasons for memory impairments seen in old age. Dentate gyrus is also one of the few regions in the brain where neural stem cells generate new neurons on a daily basis, also referred to as "adult neurogenesis". Studies have suggested that a significant fraction of newly born neurons mature, get incorporated into the existing hippocampus circuitry and contribute to learning, formation of new memories, and normal mood. However, with aging, the dentate gyrus shows decreased function with some conspicuous structural changes, which include reduced production of new neurons, diminished microvasculature implying reduced blood flow, and occurrence of hypertrophy of astrocytes and activated microglia, signs of chronic low-level inflammation. Because alterations such as reduced neurogenesis, decreased blood flow and brain inflammation can contribute to memory and mood impairments, the idea that drugs that are efficacious for mitigating these changes may
preserve memory and mood function in old age has emerged. Such drugs may be prescribed to the aging population if they are efficacious for maintaining normal cognitive and mood function in old age with no or minimal side effects.
Medical Research: What is the rationale for choosing resveratrol for preventing age-related memory dysfunction in this study?
Prof. Shetty: Administration of resveratrol, a naturally occurring polyphenol found in the skin of red grapes, red wine, peanuts and some berries, appeared suitable for counteracting age-related detrimental changes in the hippocampus. This is because, previous studies have shown that
resveratrol has ability to promote the formation of new capillaries (through pro-angiogenic effects) and to suppress oxidative stress and inflammation (via antioxidant and antiinflammatory effects) with no adverse side effects. Other studies have also reported that resveratrol can mediate extension of the life span and delayed onset of age related diseases. More importantly, a recent human study suggested that a reasonably lower dose of resveratrol intake for 26 weeks is good enough to improve memory performance as well as hippocampus functional connectivity in 23 healthy overweight older individuals (Witte et al., J. Neurosci., 34: 7862-7870, 2014).
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MedicalResearch.com Interview with:
R. Scott Turner, MD, PhD
Director of the Memory Disorders Program
Georgetown University Medical Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Turner: The resveratrol trial originated from the extensive scientific literature demonstrating that caloric restriction (consuming only 2/3 usual calories) prevents or delays diseases of aging - including Alzheimer's disease (AD) in laboratory animals. The molecular mechanism is thought to involve sirtuins - a group of genes/proteins that sense energy balance to regulate gene expression. Sirtuins are activated by caloric restriction (a mild stressor) to express genes that promote resilience of the organism. Resveratrol is a potent activator of sirtuins - thus bypassing the requirement for caloric restriction. On the opposite side of the coin - caloric excess, midlife obesity, and diabetes are strong risk factors for Alzheimer's disease. And we have long-known that resveratrol is found in red grapes, red wine, and other foods that promote general health.
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