Research Overview

The Alfred B. and Gudrun J. Kastor Neurobiology of Aging Laboratories (KNAL) were established in 1996 as an innovative multidisciplinary research program focusing on age-related alterations in brain function. KNAL is housed in 10,000 square feet on the 9th floor of Mount Sinai's Icahn Medical Institute. KNAL is directed by John H. Morrison, Ph.D., and is jointly sponsored by the Department of Neuroscience and the Brookdale Department of Geriatrics and Adult Development in which all the faculty members have joint appointments. This structure provides a neurobiology of aging research enterprise linked to both a clinical department and a basic science department, to promote our goal of building a strong basic science program devoted to the study of clinically-relevant issues related to aging.

KNAL's major scientific goal is elucidation of the anatomic, physiologic, and molecular changes in the aging brain, the mechanisms which drive those changes, and their behavioral consequences. The ultimate goal of such research is to develop interventions to enhance brain function at increasingly older ages. KNAL is also actively involved in the study of age-related diseases in the brain such as Alzheimer's disease (AD), Parkinson's disease, and amyotrophic lateral sclerosis (ALS) which are prevalent in the aging community. Toward this end, we have assembled a group of scientists dedicated to multidisciplinary interactive approaches to understand both normal and pathological aging, with the intent of promoting "successful" aging.

One special focus of KNAL is to understand the basis for the common age-related changes in memory. Problems with memory constitute the most common complaint of elderly individuals, and KNAL addresses this problem using an integrated approach involving studies of the human brain as well as animal models. Our most recent recruit, Matthew Shapiro, Ph.D., studies memory and its age-related impairment at the level of individual nerve cells and related circuits, and is particularly interested in how the activity of these circuits alters their properties over time. Peter Rapp, Ph.D., has developed elegant behavioral tests to assess specific aspects of memory which are related to specific brain cell circuits, and has demonstrated impairments in aged rodents and monkeys, similar to those observed in humans. Drs. Rapp and Morrison have begun to unravel some of the neurobiological events that underlie these age-related decrements, and have discovered that they are in many respects quite different from the degenerative processes that Patrick Hof, M.D., and Dr. Morrison have characterized in dementing illnesses such as Alzheimer's disease, or in transgenic mouse models of another neurodegenerative disorder, amyotrophic lateral sclerosis (ALS).

Hormone-brain interactions in aging is a key area where KNAL is mounting a major multi-disciplinary effort. For example, menopause is associated with a decline in cognitive function that may be attributable to the effects of the post-menopausal depletion of estrogen on the brain. Therefore, it is becoming increasingly compelling to understand the mechanisms by which estrogen impacts on brain function during aging. Andrea Gore, Ph.D., is interested in precisely these issues, and is currently studying the important role of estrogen in the aging brain in great detail. In addition, Drs. Morrison, Gore, and Rapp, along with colleagues at Rockefeller University, Rush/Presbyterian Medical Center, and UC Davis recently obtained a large Program Project Grant from NIA to investigate the neurobiological and behavioral effects of estrogen in the context of aging. In related neuroendocrine investigations, Charles Mobbs, Ph.D., is examining how impairments in the function of specific brain cells lead to health problems such as diabetes and obesity during aging, and in this regard he has developed evidence that in both humans and rodents, neurological and metabolic impairments during aging are related to an age-related decline in the hormone leptin, and he is currently examining the effects of replacing leptin during aging.

One of the many advantages of the close collaboration of the members of KNAL is that we can use many different techniques and animal models to address such fundamental problems as the key biochemical and structural characteristics that render a brain cell prone to degeneration and/or functional decline so that we can develop therapeutic strategies aimed at protecting those at risk. We will continue to build liaisons and research programs with an emphasis on the age-related functional deficits that strongly impact quality of life, and develop mechanisms to foster successful aging.