The major research focus of James L. Kirkland, M.D., Ph.D., is the impact of cellular aging (senescence) on age-related dysfunction and chronic diseases, especially developing methods for removing these cells and alleviating their effects. Senescent cells accumulate with aging and in such diseases as dementias, atherosclerosis, cancers, diabetes and arthritis, even in younger people.
The goal of Dr. Kirkland's current work is to develop methods to remove these cells to delay, prevent, alleviate or partially reverse age-related chronic diseases as a group and extend health span, the period of life free of disability, pain, dependence and chronic disease.
- Cellular senescence. Dr. Kirkland's team developed the idea that removing senescent cells may enhance health span, partly based on the observation that mice with mutations that increase life span have a lower senescent cell burden compared with that of normal mice, and that short-lived mice have more of these cells.
- Senolytic drugs. Dr. Kirkland and his team devised a novel strategy to discover the first senolytic drugs, agents that selectively eliminate senescent cells. They uncovered mechanisms that senescent cells use to protect themselves against the factors they release to kill normal cells and damage tissues near them. Dr. Kirkland's team then developed ways to transiently disable these senescent cell protective mechanisms, resulting in senescent cells "committing suicide" instead of killing cells around them. These senolytics are effective in delaying, preventing, alleviating or treating multiple conditions and diseases in mice. They are currently in clinical trials for serious senescence-related diseases, in which they have shown early signs of promise.
- Diabetes, other chronic diseases and cellular senescence. Diabetes and obesity are associated with accumulation of senescent cells in fat and other tissues. Dr. Kirkland's group is working on ways to reduce severity and alleviate the complications of diabetes by clearing senescent cells or blocking them from producing factors that cause or exacerbate dysfunction. Effects of eliminating senescent cells or the factors they release are being investigated for frailty, Alzheimer's disease, arthritis, osteoporosis, cancers and a range of other disorders in Dr. Kirkland's laboratory and with collaborators at Mayo and other institutions.
Significance to patient care
Dr. Kirkland's work is important in developing methods to enhance health span and delay onset of chronic age-related diseases as a group, rather than one at a time. These conditions, including diabetes, dementias, atherosclerosis, cancers and arthritis, among others, account for the bulk of morbidity, mortality and health care costs throughout most of the world.