Systems Biology of Aging (R01)

Systems Biology of Aging (R01)
Department of Health and Human Services
National Institutes of Healthaging-central

Section I. Funding Opportunity Description

The molecular basis of aging has been examined using numerous methods and organisms. Lifespan has been a surrogate for aging, and remains useful as a binary endpoint of the aging process (“alive versus dead” in place of quantifiable losses of function over time or advent and progression of diseases).   In this approach, an underlying assumption is that factors which influence lifespan will also influence aging, although the converse is not always true (some losses of function in aging apparently do not directly impact lifespan, and not all aging-related diseases are considered fatal). As a result of these studies on regulation of lifespan in diverse organisms, we have substantial information about individual gene-products, noncoding RNA, biochemical pathways, environmental factors and cell biological mechanisms that impact aging. We do not have similar levels of insight into the ways these factors interact to cause (or retard) aging in any organism. In addition, the focus to date has been on the conserved genes and pathways and their impact on lifespan across a range of organisms whose lifespans vary widely. Despite this, we have relatively little insight into the biological processes that result in those characteristic mean and maximum lifespans, whether those are lifespans of closely related or evolutionarily distant species. While the focus on conserved pathways is believed to be critically important for the translational potential of studies in animal models of human aging, casting a wider net to understand fundamental aspects of aging biology – irrespective of conserved genes and pathways – can also provide new insights and suggest new ways to alter the rate of aging. Systems biology of aging, using newly constructed networks rather than previously described networks or networks based – for example – on protein-protein interactions curated from the literature, is a highly ‘agnostic’ approach to uncover novel interactions and emergent properties of networks, and to generate new hypothesis about fundamental processes of aging.

The major goals of this FOA are to employ systems biology to generate new insights about the molecular mechanisms of aging, preferably at the network level of emergent properties, and also to understand the changes in relationships among network components that impact lifespan. By “emergent properties” we mean unique properties arising from the complexity of multiple and multiply interacting components which are linked in the aging network. By ‘relationships’ we mean these as generally understood to be nodes and edges in networks, but also in feedback loops of the sort elaborated extensively in studies of gene regulatory networks in developmental processes. It is important that the focus of applications should be on emergent properties and/or changing relationships of an aging network. Under this FOA, Saccharomyces cerevisiae or Caenorhabditis elegans are the experimental organisms to be used for these studies. Applicants must use the multiple PD/PI model for applications submitted to this FOA: the contact PD/PI must be an expert in systems biology and other PD/PI(s) should have expertise in the biology of aging and/or necessary high-throughput technologies using the laboratory organism for study (S. cerevisiae or C. elegans, only).

The choice to restrict studies under this FOA to Saccharomyces cerevisiae or Caenorhabditis elegans is based on two considerations: 1. Demonstration projects in the systems biology of aging were successful in validating an approach to network construction and hypothesis generation under a previously issued FOA, RFA-AG-12-011. That FOA was restricted to Saccharomyces cerevisiae because it is a single-celled organism and thus avoids issues of tissue aging. However the scope and scale of work needed to complete network construction was beyond the resources of that FOA. 2. S. cerevisiae and C. elegans are laboratory organisms for which there are in-place genetic tools for gene disruption as well as multiple alleles that increase lifespan, high-throughput technologies for single-cell and single-worm analysis in gene expression, RNA analysis, epigenetics and proteomics, and established interventions affecting lifespan which are necessary to permit a systems biology approach to aging. If the goals of this FOA are met, then the systems biology approaches developed under this FOA could be extended to other organisms, but for purposes of this FOA only two laboratory organisms may be used.

General Information

Document Type: Grants Notice
Funding Opportunity Number: RFA-AG-17-004
Funding Opportunity Title: Systems Biology of Aging (R01)
Opportunity Category: Discretionary
Opportunity Category Explanation:
Funding Instrument Type: Grant
Category of Funding Activity: Health
Category Explanation:
Expected Number of Awards: 4
CFDA Number(s): 93.866 — Aging Research
Cost Sharing or Matching Requirement: No
Posted Date: Mar 09, 2016
Last Updated Date: Mar 09, 2016
Original Closing Date for Applications: Oct 07, 2016  
Current Closing Date for Applications: Oct 07, 2016  
Archive Date: Nov 07, 2016
Estimated Total Program Funding: $1,600,000
Award Ceiling: $600,000
Award Floor:


Eligible Applicants:
For profit organizations other than small businesses
County governments
Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education
Public and State controlled institutions of higher education
City or township governments
State governments
Private institutions of higher education
Independent school districts
Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education
Native American tribal organizations (other than Federally recognized tribal governments)
Others (see text field entitled “Additional Information on Eligibility” for clarification)
Small businesses
Special district governments
Native American tribal governments (Federally recognized)
Public housing authorities/Indian housing authorities
Additional Information on Eligibility: Other Eligible Applicants include the following: Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISISs); Eligible Agencies of the Federal Government; Faith-based or Community-based Organizations; Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Indian/Native American Tribal Governments (Other than Federally Recognized); Regional Organizations; Tribally Controlled Colleges and Universities (TCCUs) ; U.S. Territory or Possession; Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Additional Information

Agency Name: National Institutes of Health
Description: This Funding Opportunity Announcement (FOA) encourages research projects with the potential to develop networks of aging using lifespan as the observable phenotype. In addition to constructing aging networks, two further important goals of this FOA are: 1. Determining what properties of an aging network change across the lifespan; 2. Using aging networks to generate and test hypotheses about fundamental questions in the biology of aging that are more likely to be answered using systems biology than by single-gene approaches. Research proposed in applications responding to this FOA will utilize either the single-cell organism Saccharomyces cerevisiae or the multicellular organism Caenorhabditis elegans, both of which have been used extensively for genetic and molecular studies on aging.Applications must include a contact PD/PI who is an expert in systems biology and other PD/PI(s) should have expertise in the biology of aging and/or necessary high-throughput technologies using the laboratory organism for study (S. cerevisiae or C. elegans, only).
Link to Additional Information:
Contact Information: If you have difficulty accessing the full announcement electronically, please contact:

NIH OER Webmaster FBOWebmaster@OD.NIH.GOV
If you have any problems linking to this funding announcement, please contact the NIH OER Webmaster


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