Cellular Senescence

The Cellular Senescence Program is a highly innovative program centered on translating recent advances in understanding the basic biology of aging in model organisms into clinical interventions. The ultimate intent is to delay the whole range of disabilities associated with aging in humans. Cellular senescence is a process through which cells that are damaged or dysfunctional stop dividing and release factors that destroy adjacent cells. This process, which normally acts as a defense against cancer and other conditions involving extensive cell accumulation, contributes to organ dysfunction in old age. In this program, we are delineating:

• Mechanisms causing cellular senescence
• How, and in what organs, senescence occurs in humans
• Its relevance to age-related disability

The program is ideally based at Mayo Clinic, capitalizing on our unique suitability and high success rate in conducting research that translates basic biological findings into strategies to treat our patients (bench-to-bedside). The program capitalizes on existing expertise and recent discoveries at Mayo Clinic and elsewhere, fostering collaborations among our investigators in ways that would otherwise not have been possible. Exciting progress has been realized in this research area, dissecting fundamental mechanisms driving aging and the onset of age-related disabilities in lower animals. The work at Mayo Clinic includes the development of mice with genes that delay or accelerate senescence, including strategies that delay onset of age-related dysfunction and diseases and that extend disability-free survival. These are the first steps strategies to delay disability and prevent the age-related diseases that commonly cause loss of independence in the elderly. We have found:

• Senescent cell accumulation in a number of tissues in aging experimental animals and humans.
• These aberrant progenitor cells secrete inflammatory factors that cause dysfunction in adjacent cells.
• Accumulation of these cells is accelerated in experimental animals with genetic mutations that cause premature aging and is delayed in animals with mutations that delay aging and age-related diseases.

Great progress has been made in understanding the fundamental mechanisms causing cellular senescence. Our Cellular Senescence program will translate our knowledge of these mechanisms into practical, clinical interventions that could push the onset of cancer, cardiovascular disease, strokes, dementias, mobility disorders, metabolic diseases and the many other conditions that become increasingly common with aging, out toward the end of the life-span. The findings hold promise of leading to a timely paradigm-shift in how chronic diseases and disabilities are prevented.