Genotype

Publication Title: 
JAMA: the journal of the American Medical Association

CONTEXT: Individuals with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. OBJECTIVE: To identify specific biological and genetic factors that are associated with or reliably define a human longevity phenotype.

Author(s): 
Barzilai, Nir
Atzmon, Gil
Schechter, Clyde
Schaefer, Ernst J.
Cupples, Adrienne L.
Lipton, Richard
Cheng, Suzanne
Shuldiner, Alan R.
Publication Title: 
JAMA: the journal of the American Medical Association
Author(s): 
Andrikopoulos, George K.
Richter, Dimitri J.
Publication Title: 
Mechanisms of Ageing and Development

Subjects with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. In a case control study, we aim to determine phenotype and genotype of exceptional longevity in a genetically homogenous population (Ashkenazi Jews), and their offspring, while an age-matched control group of Ashkenazi Jews was used as control groups.

Author(s): 
Atzmon, Gil
Rincon, Marielisa
Rabizadeh, Pegah
Barzilai, Nir
Publication Title: 
Experimental Gerontology

The SIR2/Sirt1 gene has been demonstrated as regulating lifespan in many model organisms, including yeast, Caenorhabditis elegans and rodents. These findings render the human homologue, SIRT1, a very plausible candidate as a modifier of human life expectancy. We therefore sought to investigate whether common allelic variation in the SIRT1 gene was associated with human longevity.

Author(s): 
Flachsbart, Friederike
Croucher, Peter J. P.
Nikolaus, Susanna
Hampe, Jochen
Cordes, Christina
Schreiber, Stefan
Nebel, Almut
Publication Title: 
PLoS biology

Alteration of single genes involved in nutrient and lipoprotein metabolism increases longevity in several animal models. Because exceptional longevity in humans is familial, it is likely that polymorphisms in genes favorably influence certain phenotypes and increase the likelihood of exceptional longevity. A group of Ashkenazi Jewish centenarians (n = 213), their offspring (n = 216), and an age-matched Ashkenazi control group (n = 258) were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease (CVD).

Author(s): 
Atzmon, Gil
Rincon, Marielisa
Schechter, Clyde B.
Shuldiner, Alan R.
Lipton, Richard B.
Bergman, Aviv
Barzilai, Nir
Publication Title: 
Mechanisms of Ageing and Development

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity.

Author(s): 
Terry, Dellara F.
Wyszynski, Diego F.
Nolan, Vikki G.
Atzmon, Gil
Schoenhofen, Emily A.
Pennington, JaeMi Y.
Andersen, Stacy L.
Wilcox, Marsha A.
Farrer, Lindsay A.
Barzilai, Nir
Baldwin, Clinton T.
Asea, Alexzander
Publication Title: 
Neurology

OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment.

Author(s): 
Barzilai, N.
Atzmon, G.
Derby, C. A.
Bauman, J. M.
Lipton, R. B.
Publication Title: 
Neuroscience Letters

A cholesteryl ester transfer protein (CETP) genotype (V/V homozygosity for I405V, NCBI dbSNP rs5882) has been associated with preservation of cognitive function in old age, in addition to its associations with exceptional longevity and cardiovascular disease. We tested the hypotheses that this polymorphism was associated with either level of cognitive function or lifetime cognitive change in 525 participants who took part in the Scottish Mental Survey of 1932. Participants took the same well-validated mental ability test at ages 11 and 79.

Author(s): 
Johnson, Wendy
Harris, Sarah E.
Collins, Patrick
Starr, John M.
Whalley, Lawrence J.
Deary, Ian J.
Publication Title: 
Biogerontology

The exceptional longevity of centenarians is due in part to inherited genetic factors, as deduced from data that show that first degree relatives of centenarians live longer and have reduced overall mortality. In recent years, a number of groups have performed genetic association studies on long-living individuals (LLI) and young controls to identify alleles that are either positively or negatively selected in the centenarian population as consequence of a demographic pressure. Many of the reported studies have shown genetic loci associated with longevity.

Author(s): 
Novelli, Valeria
Viviani Anselmi, Chiara
Roncarati, Roberta
Guffanti, Guia
Malovini, Alberto
Piluso, Giulio
Puca, Annibale Alessandro
Publication Title: 
JAMA: the journal of the American Medical Association

CONTEXT: Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. OBJECTIVE: To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD).

Author(s): 
Sanders, Amy E.
Wang, Cuiling
Katz, Mindy
Derby, Carol A.
Barzilai, Nir
Ozelius, Laurie
Lipton, Richard B.

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