Notice Number: NOT-RM-20-014

Key Dates
Release Date: March 12, 2020
Response Date: May 15, 2020

Issued by
Office of Strategic Coordination (Common Fund)

Purpose

Background

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.

Information Requested

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. Specifically, we welcome your responses in the following domains:

1. Methods, tools, or community resources needed to characterize the heterogeneity vs. universality of senescence features, in different cell types, both in vivo and in vitro.
2. Methods, tools or community resources needed to characterize cell senescence in both humans and animal models.
3. Methods tools, or community resources that would be required to define biomarkers of cell senescence in multiple contexts.
4. Characterizing the multiple drivers of cell senescence, both pathological and physiological (e.g., cross-talk between cell senescence and other hallmarks of aging).
5. Characterizing the health consequences of senescent cell accumulation during aging and in response to challenges such as radiation or chemotherapy.
6. Characterizing attributes of physiological senescence during normal development and wound healing and their similarities or differences compared to pathological senescence.
7. Challenges in research on senolytics and senomorphs, including pharmacology and biological challenges.
8. Best approaches to take advantage of senolytics and senomorphs, both of which represent a novel class of drugs that might play a role in combatting multiple diseases and conditions.

How to Submit a Response

Responses to this RFI will be accepted through May 15, 2020. All comments will be anonymous and must be submitted via email to CS2@nih.gov. Please include the Notice number (NOT-RM-20-014) in the subject line.

In your email, please include the bullet you are addressing (or if you are proposing a novel topic), and justification for your suggestion. Please note that we are interested in addressing both the beneficial and the deleterious effects of senescent cells, and an emphasis must be placed on the creation of resources that will benefit the research community as a whole.

Responses to this RFI are voluntary. The Government is under no obligation to acknowledge receipt of the information provided and respondents will not receive individualized feedback. This RFI is for planning purposes only and should not be construed as a solicitation or as an obligation on the part of the United States Government. NIH will use the information submitted in response to this RFI at its discretion. NIH does not intend to make any type of award based on responses to this RFI or to pay for either the preparation of information submitted or the United States Government's use of such information. The information submitted will be analyzed and may be shared internally, appear in reports or be reflected in future solicitations, as appropriate and at the Government's discretion. Proprietary, classified, confidential, or sensitive information should not be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s) or other activities. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government's use of such information.

Inquiries

Please direct all inquiries to:

Felipe Sierra, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6402
Email: sierraf@nia.nih.gov

Kevin Howcroft, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6229
Email: howcrofk@mail.nih.gov