MedicalResearch.com Interview with:
Uzma Samadani, MD, PhD
Chief of Neurosurgery, New York Harbor Health Care System
Assistant Professor, Departments of Neurosurgery, Psychiatry, Neuroscience and Physiology
Co-Director, Steven and Alexandra Cohen Veterans Center
NYU Langone Medical Center
Medical Research: What is the background for this study? What are the main findings?
Response: The purpose of this study was to determine the current and future incidence of chronic subdural hemorrhage in the United States civilian and Veterans' Administration populations. It's main findings are that, as the population ages, the incidence of subdural hemorrhage is increasing.
MedicalResearch.com Interview with:
Kamen Tsvetanov, PhD
Centre for Speech, Language and the Brain
Department of Psychology
University of Cambridge
Downing Street
Cambridge, United Kingdom
Medical Research: What is the background for this study? What are the main findings?
[caption id="attachment_12706" align="alignleft" width="300"]
Brain areas with rich blood supply lower their vascular reactivity with ageing[/caption]
Dr. Tsvetanov: Older brains may be more similar to younger brains than previously thought! In our study we have shown that changes in the aging brain previously observed using functional magnetic resonance imaging (fMRI) – one of the standard ways of measuring brain activity – may be due to changes in our blood vessels, rather than changes in the activity of our nerve cells, our neurons. Given the large number of fMRI studies used to assess the aging brain, this has important consequences for understanding how the brain changes with age and it challenges current theories of ageing.
MedicalResearch.com Interview with:
Angela L. Curl PhD MSW
School of Social Work
University of Missouri
Columbia, MO
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Curl: Often people think of stopping driving as just effecting one person: the person who stops driving. In reality, for married couples driving cessation affects both spouses. Using longitudinal data (1998-2010) from 1,457 married couples participating in the Health and Retirement Study, we found that husbands and wives who are no longer able to drive are less likely to work, and less likely to engage in formal volunteering (for charitable organizations) and informal volunteering (helping friends and neighbors not-for-pay). Having a spouse in the household who is still able to drive does reduce these negative consequences a little, but not entirely. Furthermore, the spouse who continues to drive is also less likely to continue working or volunteering following the driving cessation of their partner, presumably because he/she is providing transportation or social support to the non-driver.
MedicalResearch.com Interview with:
William Mair, Ph.D Assistant Professor
Department of Genetics and Complex Diseases
Harvard T. H Chan School of Public Health
Boston, MA 02115
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Mair: Dietary restriction, the reduction of food intake without malnutrition has been known for 80 years to prolong lifespan in organisms ranging from single celled yeast to non human primates, and early signs suggest improvement of metabolic parameters in patients undergoing clinical trials. However, negative side effects associated with low calorie intake remain, and compliance and lifestyle factors make it an unappealing therapeutic. Since calorie restriction (CR) can have remarkable protective effects against multiple age onset diseases in mouse models - ranging from cancer to neurodegeneration to metabolic disease - finding molecular mechanisms though which calorie restriction functions might provide novel therapeutic targets that promote healthy aging. Using a model system, the nematode worm C. elegans, we show that perception of energy intake in the nervous system may be as critical for the effects of low energy on aging as actual calorie intake itself. Animals expressing an active form of a protein called AMPK, which is a cellular energy sensor, were long lived despite eating normally but this longevity could be turned off or on by changes to a neurotransmitter in just a few neurons. This suggests that therapeutic targets that modulate the perception of energy status in the nervous system might provide novel ways to gain the benefit of calorie restriction and promote healthy aging.
MedicalResearch.com Interview with:
Thomas W. Buford, PhD
Assistant Professor, Division of Clinical Research
Department of Aging and Geriatric Research, University of Florida College of Medicine
Director, Health Promotion Center
University of Florida Institute on Aging
Medical Research: What is the background for this study? What are the main findings?
Dr. Buford: This study was a cross-sectional analysis of data collected from over 1000 older adults upon their entry into the Lifestyle Interventions and Independence for Elders (LIFE) study. Briefly, participants were recruited into the LIFE Study who were over 70 years of age, sedentary, and had mobility limitations. The objective of this study was to examine, at baseline prior to their participation in the study interventions, the association between daily physical activity habits and risk of major cardiovascular events (i.e. heart attack and coronary-related death). The study utilized accelerometers, devices designed to identify and quantify human movement, to measure participant’s daily activity. Predicted risk of cardiovascular events was determined using a risk score established in the Framingham Heart Study. As identified by accelerometry measures, participants spent on average 70% of their waking hours being sedentary. The major finding of the study, however, was that even extremely low-level activity was associated with an improved cardiovascular risk profile. For every 25-30 minutes a participant was sedentary per day, predicted risk was 1 percent higher. Conversely, But activity identified as slightly above sedentary — which could be light housework or slow walking — was associated with higher levels of the more beneficial kind of cholesterol, HDL, in people with no history of heart disease.
MedicalResearch.com Interview with:
Dr. Jeremy Van Raamsdon PhD
Laboratory of Aging and Neurodk egenerative Disease (LAND),
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Deptment of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan,Dep. of Biology, McGill University, Montreal, Quebec, Canada
Medical Research: What is the background for this study? What are the main findings?
Dr. Van Raamsdonk : The free radical theory of aging is one of the most widely accepted theories of aging. This theory suggests that reactive oxygen species (ROS), which are also known as free radicals, cause a type of damage, called oxidative damage, that accumulates over time to cause the functional decline associated with aging. ROS have also been proposed to play a role in many diseases including neurodegenerative disorders such as Parkinson’s disease and Huntington’s disease.
However, recent work has demonstrated that ROS are not necessarily detrimental. ROS perform functional roles in the body and thus it is possible to have too little ROS. We previously showed that increasing ROS by decreasing the levels of an antioxidant enzyme called superoxide dismutase (SOD) does not decrease lifespan even when all of the SOD genes are removed. We also showed that in some cases treatment with an antioxidant, such as Vitamin C, can lead to decreased lifespan. This finding is consistent with human clinical trials in which it has not been possible to show a beneficial effect of antioxidants on longevity.
In this paper we further examine the relationship between ROS and aging. We use a simple genetic model organism, the worm Caenorhabditis elegans, which has been used extensively in aging research, to determine how location impacts the effect of ROS on lifespan. We used a genetic approach to increase the levels of ROS in different parts of a cell and found that location is crucial in determining the effect of ROS on lifespan. Mildly increasing the levels of ROS in the mitochondria increases lifespan, while increasing ROS in the cytoplasm has the opposite effect of decreasing lifespan.
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).
MedicalResearch.com Interview with: John Tower, PhD Professor, Molecular and Computational Biology Program Department of Biological Sciences USC Dana and David Dornsife College of Letters, Arts and Sciences University of Southern California Los Angeles, CA 90089-2910 Medical Research: What is the background for this study? What are the main findings? Response: One of the main causes of aging...
MedicalResearch.com Interview with:
Dr. Jean-Pol Frippiat
Stress, Immunity and Pathogens Laboratory
Lorraine University
Vandoeuvre-lès-Nancy, France
What is the background for this study? What are the main findings?
Dr. Frippiat: Osteoporosis is associated to spaceflight. Consequently, we wondered whether changes in bone micro-structure induced by a ground-based model of spaceflight, hindlimb unloading (HU) that simulates some of the effects of spaceflight on mice, induces changes in B lymphocyte production in the bone marrow.
To this end, we analyzed both bone parameters and the frequency of cells of the B lineage in the bone marrow of young, old and HU mice. We found that HU leads to a decrease in both bone micro-structure and the frequency of B cell progenitors in the bone marrow. A major block at the pro-B to pre-B cell transition was observed indicating a decrease in the formation of B cells in the bone marrow. Interestingly, the modifications in B cell production were similar to those observed in aged mice.
These findings demonstrate that mechanical unloading, to which astronauts are subjected during spaceflight, results in a decrease in B cell differentiation that resemble age-related modifications in B lymphopoiesis.
MedicalResearch.com Interview with:
Andreas Kalogeropoulos, MD MPH PhD
Assistant Professor of Medicine (Cardiology)
Emory University School of Medicine Emory Clinical Cardiovascular Research Institute
Atlanta GA 30322
Medical Research: What is the background for this study? What are the main findings?
Dr. Kalogeropoulos: There is ongoing debate on how low should we go when it comes to dietary sodium (salt) restriction recommendations. In this study, we examined the association between self-reported dietary sodium intake and 10-year risk for death, cardiovascular disease, and heart failure in approximately 2,600 adults 71-80 years old. The subjects (women: 51.2%; white: 61.7%; black: 38.3%) were participants of the community-based Health, Aging, and Body Composition Study, which is sponsored by NIH and focuses on aging processes, i.e. was not specifically designed to address the issue of dietary salt intake. Also, it is important to note that salt intake was self-reported (not objectively measured) using a food frequency questionnaire, which underestimates salt intake. Keeping these limitations in mind, we did not observe a significant association between self-reported sodium intake and 10-year mortality, cardiovascular disease, and heart failure. Ten-year mortality was lower in the group reporting 1500–2300 mg daily sodium intake (30.7%) compared to those reporting daily intake less than 1500 mg (33.8%) or over 2300 mg (35.2%); however, this difference was not statistically significant. The 10-year event rates for cardiovascular disease (28.5%, 28.2%, and 29.7%) and heart failure (15.7%, 14.3%, and 15.5%) were also comparable across the <1500-mg, 1500-2300-mg, and >2300-mg dietary sodium intake groups.
MedicalResearch.com Interview with:
Jane Wardle
University College London
Medical Research: What is the background for this study? What are the main findings?
Dr. Wardle: Previous studies have shown that couples tend to have similar health behaviours to one another, but no studies had compared having a partner who takes up a healthy behaviour (e.g. quits smoking) with having one whose behaviour is consistently healthy (e.g. never smoked). Nor have there been other studies in the older age group – our participants were over 60 on average. We used data from 3722 couples participating in the English Longitudinal Study of Ageing (ELSA) to explore this issue for three behaviours: smoking, physical activity, and weight loss. For each behaviour, we found that when one partner changed their behaviour, the other partner was more likely to make a positive change, and the effect was stronger than having a partner whose behaviour was consistently healthy (i.e. never smoked/always exercised).
MedicalResearch.com Interview with: Annlia Paganini Hill PhD Project Scientist Biostatistician and Epidemiologist Department of Neurology, School of Medicine University of California, Irvine, Irvine, California Medical Research: What is the background for this study? What are the main findings? Response: Free radicals are formed when one exercises and when the body converts food to energy. Environmental sources...
MedicalResearch.com Interview with:
David Granville, BSc, PhD, FAHA
Professor, University of British Columbia
Scholar of the Royal Society of Canada
Director, GEM Facility, Centre for Heart Lung Innovation, St. Paul's Hospital Founder and CSO, viDA Therapeutics, Inc.
Vancouver, BC, Canada
Medical Research: What is the background for this study? What are the main findings?
Dr. Granville: My background is in cardiovascular research. In particular, how age affects blood vessels and how age affects mechanisms of blood vessel and heart injury and repair. We became interested in skin aging during a study in which we were studying the role of a protein degrading enzyme known as Granzyme B in atherosclerosis (hardening of the arteries) and aging. In these studies, we were using a genetic mouse model that is prone to accelerated aging, and knocked out Granzyme B. Although we were initially focused on the blood vessels, we also found that Granzyme B-deficient mice exhibited younger-looking skin. As we started to look into this, we became aware that UV light can induce the skin cells to produce Granzyme B. As sunlight is believed to be responsible for 80-90% of preventable skin aging, we generated a solar-simulated light box (with the similar ratios of UVA/UVB to sunlight) to assess whether Granzyme B played a role in UV-induced skin aging (aka photoaging). We exposed the mice to repetitive, low dose UV three times per week for 20 weeks. After 20 weeks we observed that Granzyme B deficient mice exhibited fewer wrinkles. We then wanted to look histologically and biochemically into how Granzyme B was affecting skin morphology. Granzyme B deficient mice exhibited greater collagen density compared to mice that possessed Granzyme B. As we looked into the mechanism in more detail, we determined that Granzyme B was cleaving a protein known as decorin. Decorin is responsible for collagen fibrillogenesis and assembling collagen into tight bundles. Loss of decorin is associated with a loss of collagen tensile strength. Interestingly, decorin also protects collagen from destruction by a protein-degrading enzyme known as MMP1. We showed in the study that by breaking down decorin, Granzyme B renders collagen susceptible to MMP1-mediated degradation. In addition, we showed that Granzyme B-fragmentation of another protein, fibronectin, led to the upregulation of MMP1 in skin fibroblasts. In summary, the paper showed that UV induced Granzyme B expression in the skin and showed that this enzyme contributes to the breakdown of extracellular matrix proteins and formation of wrinkles.
A link to the Aging Cell publication: http://onlinelibrary.wiley.com/doi/10.1111/acel.12298/pdf
MedicalResearch.com Interview with:
Paul Schimmel, Ph.D. Professor
The Skaggs Institute for Chemical Biology,
The Scripps Laboratories for tRNA Synthetase Research
Department of Molecular and Cell Biology,
The Scripps Research Institute, La Jolla, California
Medical Research: What is the background for this study? What are the main findings?
Dr. Schimmel: Resveratrol (RSV) is thought to provide health benefits by activating a protective stress response. In the paper we described a new, previously missed mechanism for its action. This mechanism is activated at much lower concentrations of resveratrol than previously described or imagined. Consequently, other mechanisms, which appear to act at higher concentrations of resveratrol, are layered over a preexisting foundation set by the newly revealed mechanism.
MedicalResearch.com Interview with:
Immaculata De Vivo PhD
Associate Professor Harvard Medical School
Director, Dana Farber/Harvard Cancer Center High Throughput Genotyping Core
Facility. Channing Division of Network Medicine
Boston, MA 02115
MedicalResearch: What is the background for this study? What are the main findings?
Dr. De Vivo: Our study found that greater adherence to the Mediterranean diet is associated with longer telomeres. Following a diet closer to the Mediterranean diet, can prevent accelerated telomere shortening. Our unique contribution to the literature is that we provide a potential molecular mechanism, preventing telomere shortening. Telomeres are bits of DNA that protect your chromosomes.
MedicalResearch: Is telomere shortening reversible?
Dr. De Vivo: Telomere shortening is a biological process, the shorten with age.
However, lifestyle choices can help to prevent accelerated shortening.
Fruits, vegetables, olive oil and nuts – key components of the Mediterranean diet have well known antioxidant and anti-inflammatory effects that could balance out the “bad effects” of smoking and obesity.
MedicalResearch.com Interview with:
Prof. Takeo Watanabe
The Fred M. Seed Professor
Cognitive, Linguistic and Psychological Sciences
Brown University
Medical Research: What is the background for this study? What are the main findings?
Prof. Watanabe: In the current study also supported by NIH, we obtained surprising results. That is, older people learn what younger people do not learn. We asked subjects to do a letter identification task at the center of a screen while another stimulus was presented in the background. This background stimulus contained a group of dots moving in one direction with noises and had nothing to do with the task. Therefore the motion was task-irrelevant. If the motion is clearly perceived, learning on the motion as task-irrelevant did not occur when subjects were college students. However, older people ended up increasing sensitivity to and, therefore learned, such task-irrelevant motion. This might sound as if the older brain worked better than the younger brain in visual perceptual learning. However, that may not be the case. Our brain capacity is limited. If our brain learned items that are not relevant to a given task and therefore are unimportant to us, there would be the risk of such unimportant items replacing important information which has already existed in the brain. Thus, learning of task-irrelevant and therefore unnecessary information could be harmful and decrease the efficiency of learning of what is important.
MedicalResearch.com Interview with:
Stephen D. Ginsberg, Ph.D., Associate Professor
Departments of Psychiatry and Physiology & Neuroscience
New York University Langone Medical Center
Center for Dementia Research
Nathan Kline Institute Orangeburg, NY 10962
Medical Research: What is the background for this study? What are the main findings?
Dr. Ginsberg: We tested the hypothesis that long-term calorie restriction positively alters gene expression within the hippocampus, a critical learning and memory area vulnerable in aging and Alzheimer’s disease. To test this hypothesis, we conducted experiments on female mice that were given food pellets 30% lower in calories than what was fed to the control group. The mice ate fewer calories derived from carbohydrates. Analyses were performed on mice in middle and old age to assess any differences in gene expression over time. Our data analysis revealed that the mice that were fed a lower calorie diet had fewer changes in approximately 900 genes that are linked to aging and memory.
MedicalResearch.com Interview with:
Sofiya Milman, M.D.
Assistant Professor of Medicine
Divisions of Endocrinology and Geriatrics
Albert Einstein College of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Milman: Aging is a major risk factor for many diseases, including cardiovascular disease, dementia, and diabetes. Yet, individuals with exceptional longevity delay the onset of most diseases and often escape from age-related illnesses altogether. Exceptional longevity is an inherited trait. A unique cholesterol profile has been previously associated with longevity and specific genetic variations. This profile included elevated levels of high-density lipoprotein (HDL) cholesterol or “good” cholesterol and large HDL particles. The present study explored whether elevated HDL cholesterol levels and genes that control HDL cholesterol can predict survival in individuals age 95 years or older.
The study found that higher levels of HDL cholesterol were related to longer survival in women, but not in men. Higher HDL cholesterol level was also seen in individuals without cognitive problems and diabetes. On the other hand, both men and women with larger HDL particle size and higher levels of APOA1, a protein component of HDL cholesterol, exhibited longer survival. Variants in two genes, the CETP and APOA1, were related to higher HDL cholesterol levels.
MedicalResearch.com Interview with:
Professor Emrah Düzel
Director, Institute of Cognitive Neurology and Dementia Research, OvG Univ. Magdeburg, Germany
Institute of Cognitive Neuroscience
University College London
Medical Research: What are the main findings of the study?
Professor Düzel: We found that even in old age, intensive and long-term (3 months) aerobic exercise can improve blood flow in the hippocampus, a brain structure that is of critical importance for memory. The increase in blood flow is evident during a resting state and this means that the exercise improves the overall perfusion of the hippocampus. Such effects had previously only been reported in young adults. As previously observed in young adults, the change in blood flow after exercise is related to the improvement of specific memory skills. We found the closest relationship between improved blood flow and recognition memory for complex objects. This is interesting because this type of memory is likely to benefit from “pattern separation”, a process that in animal studies of exercise is tightly associated with hippocampal neurogenesis.
However, we also found that the exercise-related improvement in hippocampal blood flow and in recognition memory was absent in the older seniors of our study cohort. Those who were beyond 70 did not show any improvement. We reasoned that this may have been due to higher levels of stress in the older seniors. Therefore, we investigated whether elevated serum cortisol levels dampened the benefits of exercise in the older seniors. But this was not the case making it unlikely that stress levels can account for these findings.
MedicalResearch.com Interview with:
Associate Professor Dafna Merom Ph.D
Physical Activity and Health
University of Western Sydney
Penrith NSW Australia
Medical Research: What are the main findings of the study?
Dr. Merom: In a cohort of 1667 older Australian men (mean age 76.8 years) data on incident falls were collected every four months by telephone interview. We compared the rate of falling over 48 months of follow-up of men who participated in golf, Calisthenics, lawn balls, aerobic machines and swimming. We found that only swimming was associated with 33% reduction in falls occurrence. We also found that swimmers performed better on balance tests in our baseline measurements. In particular on the postural stability test and for those whose leisure activity was only swimming, apart from walking and other lifestyle activities.
Xuemei Sui, MD, MPH, PhD
Assistant Professor, Department of Exercise Science
Division of Health Aspects of Physical Activity
Arnold School of Public Health
University of South Carolina
Columbia, SC 29208
Medical Research: What are the main findings of the study?
Dr. Sui:
First, blood pressure is inversely associated with cardiorespiratory fitness levels among men. People in higher fitness categories had lower blood pressure than those in lower fitness categories.
Second, fitness is a strong effect modifier for the systolic blood pressure aging trajectory.
A higher fitness level can significantly delay the natural age-associated increase in blood pressure.
MedicalResearch.com Interview with:
Professor Mark L. Wahlqvist, M.D., Ph.D.
Institute of Population Health Sciences, National Health Research Institutes, Taiwan
National Defense Medical Center, School of Public Health, Taiwan
Monash Asia Institute, Monash University Melbourne, Australia
Medical Research: What are the main findings of the study?
Prof. Wahlqvist: Poor appetite and dietary quality as judged by diversity separately (each by about 50%) and together (by about 80%) increase the mortality risk in older persons living in the community.