@article {1104,
	title = {Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity.},
	journal = {Aging Cell},
	volume = {8},
	year = {2009},
	month = {2009 Aug},
	pages = {460-72},
	abstract = {<p>The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) = 95.3 +/- 2.2y) and 603 average-lifespan controls (lifespan < or = 79y, mean = 75.7 +/- 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95\%CI = 0.68-0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95\%CI = 1.15-1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.</p>},
	keywords = {Aged, Aged, 80 and over, Female, Follow-Up Studies, Forkhead Box Protein O3, Forkhead Transcription Factors, Genome, Human, Genotype, Humans, Insulin, Insulin-Like Growth Factor I, Longevity, Male, Osteoporosis, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-akt, Signal Transduction},
	issn = {1474-9726},
	doi = {10.1111/j.1474-9726.2009.00493.x},
	author = {Pawlikowska, Ludmila and Hu, Donglei and Huntsman, Scott and Sung, Andrew and Chu, Catherine and Chen, Justin and Joyner, Alexander H and Schork, Nicholas J and Hsueh, Wen-Chi and Reiner, Alexander P and Psaty, Bruce M and Atzmon, Gil and Barzilai, Nir and Cummings, Steven R and Browner, Warren S and Kwok, Pui-Yan and Ziv, Elad}
}
@article {1081,
	title = {Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.},
	journal = {Exp Gerontol},
	volume = {44},
	year = {2009},
	month = {2009 May},
	pages = {350-5},
	abstract = {<p>Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15\%-20\% higher baseline IL-6 concentration per copy among CHS European-American (EA) participants (all p<10(-4)). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p=0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415--longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all three studies, the "risk" of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95\%CI 0.62-1.02; p=0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes.</p>},
	keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Case-Control Studies, Female, Genetic Variation, Genotype, Humans, Inflammation, Interleukin-6, Longevity, Male, Phenotype, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases, Risk Factors},
	issn = {1873-6815},
	doi = {10.1016/j.exger.2009.02.004},
	author = {Walston, Jeremy D and Matteini, Amy M and Nievergelt, Caroline and Lange, Leslie A and Fallin, Dani M and Barzilai, Nir and Ziv, Elad and Pawlikowska, Ludmila and Kwok, Pui and Cummings, Steve R and Kooperberg, Charles and LaCroix, Andrea and Tracy, Russell P and Atzmon, Gil and Lange, Ethan M and Reiner, Alex P}
}
