Background: The Longevity Consortium (LC) is multi-investigator, multi-institutional research group that has been funded by the National Institute of Aging since 2000. The overall initial and to a large extent continuing goal of the LC is to identify genes and genetic pathways important in human aging and longevity using data collected from human studies and animal models. The present iteration of the Consortium further focuses the goal so that the efforts are more translational in nature and geared to the identification and/or development of drugs that will slow the aging process, compress late-life morbidity and improve healthy aging.
LC organization and activity: As detailed elsewhere on the website, the LC consists of three cores (administrative, genomics and biostatistics-bioinformatics), currently two major projects (‘Subphenotypes of Exceptional Longevity and Environmental and Genetic Associations’ and ‘Critical Anti-Aging Pathways from Inter-Species Comparisons’) and three smaller ‘opportunity fund’ projects (with two more pending as of early 2015) on the roles and manner in which FOXO transcription factors (notably FOXO3a) and the various allelic forms APOE affect aging and longevity.
Historically, the Consortium has provided support for as many as five major and 11 smaller opportunity fund research endeavors. These projects represented state-of-the art, often cutting edge research on aging and longevity. For example, one the major projects explored the use of QTL analysis to identify genes associated with stress and aging in mice. Still another focused on telomere length in human aging and longevity while a third assessed associations between stress, inflammation and the genetics of human aging. Among the smaller one year projects, some of the efforts were devoted to better understanding the exceptional longevity of Okinawans, others to identifying rare sirtuin variants in the extremes of adult lifespan and still others to using chemical mutagenesis of ESC to generate stress resistant (and potentially long-lived) mice.
The LC now also includes a Translational Research Core within which there are at present two working groups (focused on APOE and FOXO3) that regularly review the progress of opportunity fund projects, discuss current literature and, most importantly, identify and help develop new research projects for opportunity fund support. Finally, the LC organizes and hosts annual (occasionally semi-annual) symposia or workshops. The nature and content of these is described below.
Research Cores: Virtually since the inception of the LC, there have been two major research support cores that have been instrumental in promoting the success of multiple research projects; ‘Bioinformatics and Biostatistics’ (BBS) headed by Dr. Nik Schork (Professor and Director of Human Biology at the J. Craig Venter Institute, UCSD) and ‘Genomics’ led by Pui Kwok (with Ludmila Pawlikowska) at the University of California, San Francisco. In the case of the latter, the core was particularly important early-on in doing SNP analysis of genes associated with the Insulin/IGF-1 pathway. Currently, it is performing RNASeq on samples from multiple bird species using material provided by the Miller inter-species study. These data are, in turn, being analyzed by Schork and his colleagues of BBS. Earlier the BBS contributed, importantly, to the analysis of SNP data related to the insulin/IGF-1 pathway, and aging and longevity in Okinawans. In a number of instances and constituting a major contribution, the BBS developed new analytic tools to accomplish the latter tasks.
Major Research Projects Funded by the Longevity Consortium in the Past: While there are currently only two major LC projects underway, historically there have been as many as five covering a range of topics; from ‘Insulin Signaling Gene Expression in Long-live Mice’ (Andrez Barkte, University of Southern Illinois) to ’Stress, Inflammation and Genetics of Human Longevity’ (Alex Reiner, University of Washington, Seattle) to ‘The Role of Telomeres in Human Longevity and Aging (Richard Cawthon, University of Utah).
Symposia and workshops: Since 2001, the LC has organized 20 meetings involving a total of 179 speakers, some presenting on more than one occasion. Until recently, the average meeting involved about 50 attendees, including speakers, discussants and NIA staff. Over the years, a wide range of topics related to aging and longevity have been covered (see link to previous programs), representing some of the most exciting and cutting edge work being done at the time. For example, LC meetings were among the first to consider Klotho as a longevity regulating gene, to consider the role of heat shock proteins in aging, to explore the role of epigenetics and DNA methylation in regulating aging and to consider the role of cellular senescence in cancer and aging. Most recently, the LC held a workshop to discuss, in depth, the genetics and functional genomics of FOXO3, one of few genes whose variants are most consistently with exceptional longevity.
By design, most meetings provided an almost unique interdisciplinary approach and included a combination of basic, translational, computational and clinical science. The symposia also provided a platform for LC funded investigators to present and discuss the progress of their research. Equally importantly, they also provided an essential venue for informal discussions leading, in a number of cases, to new collaborations and joint research projects.