The LC was organized in 1999 to identify genes that affect longevity and aging in humans. In its initial phase (Phase I), members of a LC planning committee exchanged information about research methods and results from several disciplines, formed cross-disciplinary collaborations, and identified potential biological pathways that may harbor genetic variants that affect human lifespan. This phase, which was supported by a planning grant from the NIA, brought together researchers interested in longevity and aging from a variety of disciplines, including laboratory scientists who study longevity in model systems; epidemiologists who have enrolled and followed large cohorts of elderly people; experts in genomic methods; biostatisticians interested in the analysis of the associations between genetic data and complex traits; demographers who study patterns of mortality and life expectancy; and gerontologists and geriatricians. The planning committee included many members of the current LC. The planning process led to a number of successful collaborations and led to Phase II of the Consortium, also supported by the NIA. In Phase II, the LC took three approaches to study longevity: a.) identify common genetic variants associated with survival in candidate pathways in adults > 90 years old; b.) identify genes association with long life span in mice; and c.) study the associations between telomere length and human longevity. Phase II included 5 projects and 3 Cores, involved a broad consortium of scientists to test hypotheses that: 1. common single nucleotide polymorphisms (SNPs) in insulin signaling pathways are associated with exceptional survival; 2. common SNP’s in pathways involved in inflammation and thrombosis are associated with exceptional survival; and 3. longer telomere length is associated with exceptional survival; 4. the effects of growth hormone and insulin signaling in lifespan determination of mouse models, and 5. analyzed genetic variants associated with cellular stress resistance and longevity in wild-type mice. Phase III of the consortium pursued more refined studies focusing on Centenarians, cross-species studies and integrated data analyses and, despite a reduced budget, has been highly productive . In addition, the LC researchers secured an additional grant (U24AG051129) focusing on drug discovery which will complement the proposed research as discussed in section II.8.
Central Theme for New Funding Period
The LC will continue its focus on identifying genetically-mediated factors that contribute to human longevity, both in terms of lifespan and healthspan. However, the newly-framed LC will have a much stronger emphasis on the integration, validation and pre-clinical translation of results than before, using a wide- variety of approaches (see Projects and Cores here). The central and guiding theme of the LC will be to identify genetic and molecular factors that, in aggregate, causally influence human longevity and that, either individually or as part of a broader molecular pathway or process, might be amenable to pharmacological manipulation. LC investigators have, over the previous two decades, made substantive contributions to the state-of-the-knowledge of human aging and longevity.
- Kahn A, Longevity Consortium (2011) The Longevity Consortium: Harnessing diverse approaches to understand the genetic basis of human longevity and healthy aging. An introduction to a series of articles. Ageing Res Rev 10: 179–180 [ PubMed ]