Advancements in Aging - Summer 2014

Summer 2014

Exploring the Link Between Chronic Kidney Disease and Muscle Wasting
Kidney dialysis eliminates waste and unwanted water from the blood, but it may also promote inflammation and induce muscle breakdown; increased inflammation after dialysis initiation may promote muscle wasting and decline.

Muscle wasting, a condition often associated with chronic kidney disease, drastically reduces patients' quality of life and increases their mortality risk. Complicating matters for many of those who come to Montefiore for care is that there is no known treatment for this loss of lean body mass. But answers may not be too far off.

Montefiore Einstein researcher Matthew Abramowitz, MD is currently investigating how inflammation affects changes in patients' skeletal muscle structure and function as they begin kidney dialysis.

Dr. Abramowitz's NIH-Funded study of 100 patients over a five-year period—one of the first research studies to follow patients as they transition into dialysis—will:

Examine muscle wasting at biochemical, physiologic and clinical levels;
Define how inflammation relates to changes in skeletal muscle physiology, lean body mass and physical function in patients who have not yet begun dialysis; and
Determine how transitioning to dialysis affects these parameters.

Dr. Abramowitz notes that it is often difficult to predict whether starting dialysis will improve muscle wasting and functional impairment in a particular patient, especially those who are older. However, by focusing on the role of inflammation in this process, he hopes to identify parameters that will help develop better prognostic tools and, ultimately, new treatment options for these patients.

Matthew Abramowitz, MD, Attending Physician, Medicine; and Assistant Professor, Medicine (Nephrology) and Epidemiology & Population Health, Albert Einstein College of Medicine.

Low Growth Hormone Levels May Be Responsible for Exceptional Longevity
When it comes to human growth hormone (hGH), the old adage "less is more" may apply for many older adults. Indeed, a study conducted by Montefiore endocrinologists Nir Barzilai, MD; Sofiya Milman, MD; and other researchers has shown that lower levels of hGH predict enhanced longevity for older adults.

Beginning in middle age, the pituitary gland slows down production of a naturally occurring growth hormone called IGF-1. It's hGH that prompts the liver and other organs to make IGF-1, which affects tissues and organs throughout the body. The study—conducted at Einstein and published in the official journal of the Anatomical Society, Aging Cell showed for the first time that low levels of IGF-1 may be linked to exceptional longevity in women, particularly those with a history of cancer.

The Montefiore and Einstein researchers tested whether IGF-1 levels in men and women between the ages of 90 and 99 years old could predict how much longer each had to live. Women with IGF-1 levels below the median survived significantly longer than women with levels above the median. In addition, in both men and women with a history of cancer, lower IGF-1 levels predicted longer survival.

A similar paper—published in the March 2014 issue of the journal Cell—also proposed a benefit to lower IGF-1 levels before age 65. However, our researchers reveal that this benefit extends well into old age. "Our results suggest that growth hormone for healthy aging might not be a good idea," Dr. Barzilai says. "The same hormones may have a different effect across the life span, and the outcome may be different."

Dr. Barzilai is Attending Physician, Medicine; Professor, Medicine (Endocrinology); Director, Institute for Aging Research; Director, Nathan Shock Center of Excellence in the Basic Biology of Aging; and the Ingeborg and Ira Leon Rennert Chair of Aging Research, Einstein.

Dr. Milman is Attending Physician, Medicine; and Assistant Professor, Medicine (Endocrinology and Geriatrics), Albert Einstein College of Medicine.

Improving the Effectiveness of Risk Identification and Fall Prevention Strategies
What would cause a moderately active, healthy 75-year-old man who enjoyed participating in social activities to become homebound? The answer, unfortunately is simple: a fall. Each year, one in three community-dwelling adults over age 65 and one in two adults over age 80 fall, with devastating results such as loss of independence, institutionalization and premature mortality.

The NIH-funded research by Joe Verghese, MD, is focused on gaining a deeper understanding of the biological mechanisms and nervous system components responsible for falls to improve the effectiveness of risk identification and fall prevention strategies.

Mobility, executive control and fatigue are closely linked through the frontal cortex of the brain. According to Dr. Verghese, in older adults, factors such as inflammation and oxidative stress in the body may initiate arterial blockage, which leads to vascular damage in this part of the brain that in turn may increase risk of falls.

Current research has primarily focused on the clinical predictors of falls like gait changes or foot placement. Fall prevention strategies based on this research have had limited success. This new study will shift the focus from clinical predictors of falls to underlying biological mechanisms, as this type of mechanistic approach has been limited in falls research.

The five-year study, which will build on an extensive collection of prior and current cognition and mobility research, will include more than 500 participants age 65 and older, many of whom are enrolled in Montefiore's ongoing Central Control of Mobility in Aging study examining the effects of executive control and fatigue on older adults' ability to successfully maintain mobility.

The research uses rigorous evaluation methods, many of which were developed and validated in Dr. Verghese's other aging studies, to assess the fall risk of these adults. With state-of-the-art neuroimaging techniques, researchers will examine small blood vessels in the brain to establish how abnormalities in this complex network may contribute to fall risk. They will implement innovative functional near-infrared spectroscopy, a non-invasive imaging method that uses light to monitor brain blood flow and measure blood oxygenation levels in the brain, to assess brain activity during walking and establish the contribution of the prefrontal cortex to falls.

Results of Dr. Verghese's study will cultivate more efficient risk identification methods and improve the efficacy of current fall interventions.

Dr. Verghese is Chief, Integrated Divisions of Cognitive and Motor Aging (Neurology) and Geriatrics (Medicine), Montefiore; and Professor, Medicine (Geriatrics) and Neurology; Murray D. Gross Memorial Faculty Scholar in Gerontology; and Director, Resnick Gerontology Center, Einstein.

Collaborative Recall May Improve Age-Related Memory Decline
What happens when we remember together? The ongoing research of Helena Blumen, PhD, suggests that collaborative recall is a social activity that could be used to maintain or improve memory in aging—both for healthy older adults and for individuals with mild cognitive impairment who are at an increased risk for developing Alzheimer's disease and other forms of dementia.

Dr. Blumen's research could support the development of non-invasive, cost-efficient interventions that impact older U.S. adults by supporting the preservation of their memory. The study found that collaborative recall improved individual recall after short and long delays in both younger and older adults. In addition, repeated collaboration benefited these adults more than repeatedly working alone up to a week later.

Working in groups of three, study participants reviewed a list of words and then were asked to recall the words, either alone or in their groups. Study participants were asked to recall their words five minutes following collaboration and then one week following collaboration.

Collaboration can benefit later individual memory by providing additional study exposure (re-exposure) or additional retrieval opportunities (cross-cuing). Dr. Blumen assesses cross-cuing by examining whether the amount of increase or improvement between repeated collaborative recall trials is greater than that between repeated individual recall trials.

Collaboration can have negative effects that obscure the benefits of re-exposure and cross-cuing. Individuals are often disrupted by the input of others, for example, which makes them contribute less information than they are capable of providing alone. However, the information that the individual fails to recall during collaboration is often recovered when that person is removed from the group setting and begins to work alone.

Dr. Blumen is Assistant Professor, Medicine (Geriatrics), Einstein.