We have strengthened our revised proposal in several major ways. First, we have expanded our genetic sequencing of the extreme phenotype of centenarians (with appropriate controls) to include the entire human exome, in addition to regulatory/conserved regions of more genes (~1,000) selected by our Scientific Advisory Committee, based on work from model systems and previous genome-wide association studies (GWAS) for longevity. Second, instead of creating a Gene Function Core, we will analyze and characterize in silico the variants we discover in order to identify the best candidates for subsequent functional studies. Third, after careful consideration of reviewers'comments and concerns about the proposed in vitro work, we decided to defer several proposals for in vitro studies of specific pathways-insulin signaling, TOR, mitochondria and energy-sensing, micro- and regulatory RNA, and proteostasis?until we have identified the best candidates for functional studies. In addition, we have modified the remaining projects and cores in response to the previous reviews. We are excited that the next phase of the Longevity Consortium (LC) will have a substantial impact on research on aging and chronic degenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AG023122-09S1
Application #
8927231
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Rossi, Winifred K
Project Start
2003-12-01
Project End
2016-06-30
Budget Start
2014-09-30
Budget End
2015-06-30
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
California Pacific Medical Center Research Institute
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94107
Sebastiani, Paola; Andersen, Stacy L; McIntosh, Avery I et al. (2016) Familial Risk for Exceptional Longevity. N Am Actuar J 20:57-64
Ma, Siming; Upneja, Akhil; Galecki, Andrzej et al. (2016) Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity. Elife 5:
Zeng, Yi; Nie, Chao; Min, Junxia et al. (2016) Novel loci and pathways significantly associated with longevity. Sci Rep 6:21243
Wang, Bo; Merillat, Sean A; Vincent, Michael et al. (2016) Loss of the Ubiquitin-conjugating Enzyme UBE2W Results in Susceptibility to Early Postnatal Lethality and Defects in Skin, Immune, and Male Reproductive Systems. J Biol Chem 291:3030-42
Bae, Harold; Monti, Stefano; Montano, Monty et al. (2016) Learning Bayesian Networks from Correlated Data. Sci Rep 6:25156
Bhutani, Kunal; Nazor, Kristopher L; Williams, Roy et al. (2016) Whole-genome mutational burden analysis of three pluripotency induction methods. Nat Commun 7:10536
Ismail, Khadija; Nussbaum, Lisa; Sebastiani, Paola et al. (2016) Compression of Morbidity Is Observed Across Cohorts with Exceptional Longevity. J Am Geriatr Soc 64:1583-91
Sebastiani, Paola; Nussbaum, Lisa; Andersen, Stacy L et al. (2016) Increasing Sibling Relative Risk of Survival to Older and Older Ages and the Importance of Precise Definitions of ""Aging,"" ""Life Span,"" and ""Longevity"". J Gerontol A Biol Sci Med Sci 71:340-6
Yin, Xianyong; Wineinger, Nathan E; Wang, Kai et al. (2016) Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population. J Psychiatry Neurosci 41:413-421
Matteini, Amy M; Tanaka, Toshiko; Karasik, David et al. (2016) GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell 15:792-800

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