Program Project on Aging

Research into the molecular, genetic, and cellular aspects of aging has greatly expanded our understanding of the basic processes that contribute to both longevity and age-related diseases.  The primary focus of this Program is the assertion that age-dependent increases in oxidative stress and alterations in cellular handling of calcium converge to produce several of the well-known manifestations of aging, such as progressive muscle weakness, compromised cognitive performance, and declining immune function.  Oxidative stress has been invoked as an important mechanism for cell degeneration in many human diseases, including conditions such as Alzheimer’s and Parkinson’s disease.  Formation of high levels of oxidants in cells in the body is also linked to loss of control of calcium levels inside cells.  We have shown such loss of control of calcium levels with advancing age, in particular in brain nerve cells.  In addition to the loss of control of calcium, we have found clear evidence of increased oxidative stress with aging.  During the period of funding of this Program Project, we have developed unique capabilities in the analysis of protein markers of oxidative stress and characterized the effects of oxidation and aging on critical calcium-regulating proteins.  During the decade of funding of the Program, enormous shifts have occurred in the overall research enterprise, primarily due to the sequencing of the human genome and development of remarkable technologies for high throughput analyses of genomic, proteomic, and signaling events occurring in cells and tissues.  As a result, the strategies that we are now using to study the aging process have changed to take advantage of the latest research advances in these fields.  In the planned new phase of this Program, we will continue the investigations into aging, oxidative stress and calcium regulation by focusing our activities on three projects and two scientific cores.  We will concentrate on the molecular causes of loss of muscle mass and strength and of nerve cell degeneration and loss of memory as a result of advancing age.

-Dr. Elias Michaelis