THE LONGEVITY CONSORTIUM (LC). Multiple studies of model organisms and humans have suggested that genetic variants, proteins, metabolites, as well as other biomolecules and molecular- physiologic processes, could play roles in mediating longevity, healthspan, and age-related disease in humans. Unfortunately, the direct relevance of many of these factors to human longevity, healthspan and age-related disease is uncertain, as is the amenability of these factors to pharmacological modulation. Therefore, well-integrated and sophisticated research strategies are needed to determine the degree to which various factors both influence human longevity and are amenable to pharmacological manipulation. The Longevity Consortium (LC) has a history of precedent-setting studies seeking to identify factors that influence human longevity and healthspan and has recently redefined its goals and research strategies to achieve an appropriate level of integration and sophistication to elucidate additional factors affecting longevity, as well as their interactions and translatability into targets for pharmacotherapeutic manipulation. To enable appropriate integration in human longevity research, the LC will exploit a multiple investigator structure with 5 interlinked research projects and 3 integrative cores. These projects and cores will include: A cross-species project focusing on cellular and organismal phenotypes led by Richard Miller (referred to as the Miller-Mice/Cell project hereafter); a metabolomics project led by Oliver Fiehn (Fiehn-Metabolomics); a Centenarians project co-led by Thomas Perls and Paola Sebastiani (Perls- Centenarian); a proteomics project led by Eric Orwoll (Orwoll-Proteomics) and a disease context project led by Nicholas Schork (Schork-Disease Context). The cores include a Systems Biology core led by Nathan Price (Price-Systems), a Chemoinformatics core led by Thomas Girke (Girke-Chemoinformatics), and an administrative core with an overall administrative component led by Steve Cummings (Cummings-Admin) and a scientific integration component led by Nicholas Schork. Drs. Cummings and Schork, as Multiple PIs, will share responsibility for the overall leadership of the LC effort. The proposed LC will complement, and partner with, an NIA-funded U24 project (U24AG051129) involving many LC investigators to construct a website for data dissemination. 1

Public Health Relevance

The Longevity Consortium (LC) renewal proposal is rooted in the belief that integrated approaches to the discovery of factors affecting human longevity must be pursued. The proposed LC research will therefore include 5 research projects and 3 cores, all focusing on, and leveraging, very complementary high-throughput assays, large cohorts and novel analytic methods. An emphasis will be placed on systems biology and chemoinformatics analysis to help place the findings of each project into more coherent views of the molecular pathways and processes affecting longevity and their amenability to pharmacologic manipulation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19AG023122-11A1
Application #
9632486
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Dutta, Chhanda
Project Start
2004-09-30
Project End
2023-05-31
Budget Start
2018-09-30
Budget End
2019-05-31
Support Year
11
Fiscal Year
2018
Total Cost
Indirect Cost
Name
California Pacific Medical Center Research Institute
Department
Type
DUNS #
071882724
City
San Francisco
State
CA
Country
United States
Zip Code
94107
Brown, Abigail K; Webb, Ashley E (2018) Regulation of FOXO Factors in Mammalian Cells. Curr Top Dev Biol 127:165-192
Zeng, Yi; Nie, Chao; Min, Junxia et al. (2018) Sex Differences in Genetic Associations With Longevity. JAMA Netw Open 1:
Schork, Nicholas J; Raghavachari, Nalini; Workshop Speakers and Participants (2018) Report: NIA workshop on translating genetic variants associated with longevity into drug targets. Geroscience 40:523-538
Ding, Kuan-Fu; Finlay, Darren; Yin, Hongwei et al. (2018) Network Rewiring in Cancer: Applications to Melanoma Cell Lines and the Cancer Genome Atlas Patients. Front Genet 9:228
Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren et al. (2018) Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis. Oncotarget 9:5044-5057
Perls, Thomas T (2017) Male Centenarians: How and Why Are They Different from Their Female Counterparts? J Am Geriatr Soc 65:1904-1906
Pickering, Andrew M; Lehr, Marcus; Gendron, Christi M et al. (2017) Mitochondrial thioredoxin reductase 2 is elevated in long-lived primate as well as rodent species and extends fly mean lifespan. Aging Cell 16:683-692
Ding, Kuan-Fu; Finlay, Darren; Yin, Hongwei et al. (2017) Analysis of variability in high throughput screening data: applications to melanoma cell lines and drug responses. Oncotarget 8:27786-27799
Sebastiani, Paola; Bae, Harold; Gurinovich, Anastasia et al. (2017) Limitations and risks of meta-analyses of longevity studies. Mech Ageing Dev 165:139-146
Sebastiani, Paola; Thyagarajan, Bharat; Sun, Fangui et al. (2017) Biomarker signatures of aging. Aging Cell 16:329-338

Showing the most recent 10 out of 202 publications