Paul F. Glenn Laboratories for Senescence Research

Overview

The Paul F. Glenn Laboratories for Senescence Research at Mayo Clinic represent a collaboration among four labs within the Cellular Senescence Program that engage in aging-related research.

Specifically, the four labs explore how age-related diseases and disorders are affected by senescent cells and how eliminating senescent cells could improve health and extend both life span and health span, the healthy, productive time in life.

Mayo Clinic researchers have found that inhibition of senescence or disposal of senescent cells delays or slows several age-related pathologies with no overt side effects. This discovery opened a new field of senescent cell research that the Glenn Laboratories will help advance, potentially leading to new therapies for age-related diseases.

Areas of research

The Glenn Laboratories investigate the identities and properties of senescent cells that accumulate with aging and at the sites within the body of age-related pathologies, as well as the potential therapeutic effects of their clearance.

Researchers believe that it's imperative to understand the fundamental mechanisms driving aging and to develop interventions that may delay age-related dysfunction and maximize the number of years without serious or chronic illnesses.

Mayo Clinic is pioneering a strategy to improve health span, working on the concept that aging and age-related disease are caused at least in part by the accumulation of senescent cells in tissues and organs that occurs with aging.

Senescent cells are cells that have lost the ability to divide in response to various stimuli that increase the risk of malignant cell transformation. Senescent cells secrete numerous biologically active molecules, such as cytokines, chemokines, growth factors and proteinases, collectively referred to as the senescence-associated secretory phenotype (SASP). This is thought to disturb tissue architecture and disrupt the functionality of neighboring cells.

The Glenn Laboratories for Senescence Research focus on two central themes.

Basic biology of cellular senescence

Current knowledge of the basic mechanisms by which senescent cells develop and act is almost exclusively based on research in cultured cells isolated from an organism.

Complementation and extension of in vitro studies in humans and model organisms such as mice have been problematic, mainly because senescent cells residing in tissues and organs are relatively low in number and difficult to detect and collect.

The Glenn Laboratories collaboration is working to bypass these limitations and fill the critical gaps in knowledge by using innovative approaches in mice. The underlying central hypothesis is that the composition of the senescence-associated secretory phenotype is a key determinant in the development of age-related diseases.

Cellular senescence and chronic age-related disease

Mayo Clinic researchers hypothesize that cellular senescence plays a causal role in the initiation or progression, or both, of such chronic diseases as heart disease, hypertension, stroke, emphysema, cancer, diabetes, osteoarthritis and dementia. Studies showing that senescent cells accumulate at sites of osteoarthritis, atherosclerosis and Alzheimer's disease support this hypothesis.

The Glenn Laboratories are using well-established mouse models for chronic age-related human diseases in combination with transgenes that inducibly clear senescent cells to broadly test this hypothesis and to explore the preventive and therapeutic effects of senescent cell clearance for these diseases.

Glenn Laboratories leadership

Photograph of Jan van Deursen, Ph.D.

Jan van Deursen, Ph.D., researcher at Mayo Clinic

Director: Jan van Deursen, Ph.D.

Jan van Deursen, Ph.D., is a consultant in the Division of Community Pediatric and Adolescent Medicine and in the Department of Biochemistry and Molecular Biology at Mayo Clinic. He is the Vita Valley Professor of Cellular Senescence, a Mayo Clinic named professorship.

Dr. van Deursen's research focuses on the drivers of senescence and aging and exploring interventions that delay age-related disease and dysfunction.

Photograph of James L. Kirkland, M.D., Ph.D.

James L. Kirkland, M.D., Ph.D., researcher and clinician at Mayo Clinic

Associate director: James L. Kirkland, M.D., Ph.D.

James L. Kirkland, M.D., Ph.D., is a consultant in the Division of General Internal Medicine and in the Department of Physiology and Biomedical Engineering at Mayo Clinic. He is director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and is recognized with a named professorship, the Noaber Foundation Professor of Aging Research.

Dr. Kirkland's research focuses on age-related changes in adipose tissue, including the connection between cellular senescence and type 2 diabetes.

Photograph of Darren J. Baker, Ph.D.

Darren J. Baker, Ph.D., researcher at Mayo Clinic

Associate director: Darren J. Baker, Ph.D.

Darren J. Baker, Ph.D., is an associate consultant in the Division of Pediatric Research Laboratories at Mayo Clinic. He is recognized as a Brookdale Leadership in Aging Fellow and an Ellison Medical Foundation New Scholar In Aging.

Dr. Baker's research focuses on the involvement of senescent cells in the processes of aging, with an emphasis on stem cell senescence and neurodegenerative disease.

Photograph of Nathan K. LeBrasseur, Ph.D.

Nathan K. LeBrasseur, Ph.D., researcher at Mayo Clinic

Associate director: Nathan K. LeBrasseur, Ph.D.

Nathan K. LeBrasseur, Ph.D., is a member of the Robert and Arlene Kogod Center on Aging at Mayo Clinic. He has faculty appointments in the Department of Physical Medicine and Rehabilitation and the Department of Physiology and Biomedical Engineering at Mayo Clinic.

Dr. LeBrasseur directs bench-to-bedside (translational) research that focuses on the molecular regulation of muscle growth and metabolism, with an emphasis on cellular senescence. He also collaborates with Dr. Kirkland on the role of cellular senescence in type 2 diabetes.