About the Group
Cellular senescence, classically defined as proliferatively competent cells that have attained a state of permanent proliferative arrest associated with altered gene expression and metabolic activity, is thought to be a central player underlying multiple chronic diseases, pathologic conditions, and the aging process. Senescent cells have been shown – or are suspected – to play a role in atherosclerosis, cancer, cardiac dysfunction, kidney dysfunction, neurodegeneration, pulmonary fibrosis and many other diseases, including conditions such as frailty and sarcopenia. On the other hand, cells with similar phenotypes and biomarkers have been shown to be important players during embryogenesis, parturition and, in adults, wound healing. The discovery that senescent cells accumulate with age and produce a robust Senescence-Associated Secretory Phenotype (SASP) characterized by a pro-inflammatory and tissue remodeling set of both soluble and vesicle-secreted proteins, has led to a renewed interest in this field.
Subsequent work focused on identification of senolytics (drugs that preferentially remove senescent cells) and senomorphs (drugs that suppress the SASP without affecting cell viability). Preliminary studies suggest that clearing senescent cells in older patients may be beneficial to healthspan. In addition, it is also believed that the senescent program might provide a means to stop the proliferation of cancer cells. As powerful as this mechanism appears to be within the context of cancer, accumulation of senescent cells during aging represents a case of antagonistic pleiotropy: a process that is beneficial in the young but has negative consequences in old organisms that are beyond the power of evolutionary selection. These observations collectively provide a strong rationale for exploring avenues to harnessing cellular senescence phenomena for human health, disease and lifespan.
In spite of the progress of the past few years, it is clear that our knowledge of the mechanisms responsible for cellular senescence in tissues and organs is still limited, as is our understanding of how this process is manifested and could be harnessed for human health. In order to help identify the needs and priorities in this area of science, and plan future activities and initiatives that can most significantly impact biomedical research, the Cellular Senescence Working Group of the NIH Common Fund is seeking comments from the global community regarding conceptual, technical or methodological barriers limiting progress and to help prioritize research activities or community resources that are most likely to propel this field forward for the greater benefit of the biomedical research community.
The NIH is considering the possibility of developing a Common Fund program to address the role of senescent cells in health and disease. In spite of the burgeoning efforts already in the field attempting to test therapies based on attacking senescent cells, it has become clear that many aspects of cell senescence research are currently in need of answers before the full potential of such therapies can be safely developed in humans. As part of the initial planning process, we are requesting input from the scientific community on the challenges in this field that can best be addressed through a concerted and coordinated effort.