Haplotypes

Publication Title: 
Experimental Gerontology

The brown fat specific UnCoupling Protein 1 (UCP1) is involved in thermogenesis, a process by which energy is dissipated as heat in response to cold stress and excess of caloric intake. Thermogenesis has potential implications for body mass control and cellular fat metabolism. In fact, in humans, the variability of the UCP1 gene is associated with obesity, fat gain and metabolism. Since regulation of metabolism is one of the key-pathways in lifespan extension, we tested the possible effects of UCP1 variability on survival.

Author(s): 
Rose, Giuseppina
Crocco, Paolina
D'Aquila, Patrizia
Montesanto, Alberto
Bellizzi, Dina
Passarino, Giuseppe
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: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Recently, chromosome 4q25 was linked to exceptional human longevity, and a haplotype of the positional candidate microsomal transfer protein (MTP) gene was associated to the phenotype in U.S. Caucasians. We investigated whether linkage to 4q25 could be detected in 164 nonagenarian sibships of the Leiden Longevity Study. Additionally, we compared the MTP -493G/T and Q95H allele and haplotype frequencies in the Leiden Longevity Study (379 nonagenarians, 525 of their offspring, and 251 partners of their offspring) and in the Leiden 85-Plus Study (655 octogenarians and 244 young controls).

Author(s): 
Beekman, Marian
Blauw, Gerard Jan
Houwing-Duistermaat, Jeanine J.
Brandt, Bernd W.
Westendorp, Rudi G. J.
Slagboom, P. Eline
Publication Title: 
PloS One

BACKGROUND: Longevity is a multifactorial trait with a genetic contribution, and mitochondrial DNA (mtDNA) polymorphisms were found to be involved in the phenomenon of longevity. METHODOLOGY/PRINCIPAL FINDINGS: To explore the effects of mtDNA haplogroups on the prevalence of extreme longevity (EL), a population based case-control study was conducted in Rugao--a prefecture city in Jiangsu, China. Case subjects include 463 individuals aged > or = 95 yr (EL group).

Author(s): 
Cai, Xiao-yun
Wang, Xiao-Feng
Li, Shi-lin
Qian, Ji
Qian, De-gui
Chen, Fei
Yang, Ya-Jun
Yuan, Zi-yu
Xu, Jun
Bai, Yidong
Yu, Shun-Zhang
Jin, Li
Publication Title: 
The Journal of Clinical Endocrinology and Metabolism

CONTEXT: Exceptional longevity is associated with raised serum TSH. OBJECTIVE: The aim of this study was to examine whether offspring of people with exceptional longevity have elevated serum TSH and whether specific single nucleotide polymorphisms (SNPs) in the TSH-B gene and TSH receptor (TSHR) gene are associated with this phenotype. DESIGN/SETTING/PATIENTS: We measured serum TSH and free T(4) in Ashkenazi Jewish centenarians (n = 232; median age, 97 yr), their offspring (n = 366; median age, 69 yr), and age-matched controls without familial longevity (n = 163; median age, 70 yr).

Author(s): 
Atzmon, Gil
Barzilai, Nir
Surks, Martin I.
Gabriely, Ilan
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC.

Author(s): 
Atzmon, Gil
Cho, Miook
Cawthon, Richard M.
Budagov, Temuri
Katz, Micol
Yang, Xiaoman
Siegel, Glenn
Bergman, Aviv
Huffman, Derek M.
Schechter, Clyde B.
Wright, Woodring E.
Shay, Jerry W.
Barzilai, Nir
Govindaraju, Diddahally R.
Suh, Yousin
Publication Title: 
Aging Cell

The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity.

Author(s): 
Jazwinski, S. Michal
Kim, Sangkyu
Dai, Jianliang
Li, Li
Bi, Xiuhua
Jiang, James C.
Arnold, Jonathan
Batzer, Mark A.
Walker, Jerilyn A.
Welsh, David A.
Lefante, Christina M.
Volaufova, Julia
Myers, Leann
Su, L. Joseph
Hausman, Dorothy B.
Miceli, Michael V.
Ravussin, Eric
Poon, Leonard W.
Cherry, Katie E.
Welsch, Michael A.
Georgia Centenarian Study and the Louisiana Healthy Aging Study
Publication Title: 
Age (Dordrecht, Netherlands)

Mitochondria produce cellular energy but also free-radicals, which damage cells despite an array of endogenous anti-oxidants. In Northern Europe, the mitochondrial haplogroup J has been related to longevity in nonagenarians and centenarians but also with age-related disease. Hypertension is an important contributor to atherosclerotic-related diseases and its pathogenesis is associated with increased oxidative stress.

Author(s): 
Rea, Irene Maeve
McNerlan, Susan E.
Archbold, G. Pooler
Middleton, Derek
Curran, Martin D.
Young, Ian S.
Ross, Owen A.
Publication Title: 
Aging Cell

?-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of ?-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the ?-adrenergic signaling pathway are associated with human longevity. We performed a 10-year follow-up study of the Chinese longitudinal healthy longevity survey. The Han Chinese population in this study consisted of 963 long-lived and 1028 geography-matched young individuals.

Author(s): 
Zhao, Ling
Yang, Fan
Xu, Ke
Cao, Huiqing
Zheng, Gu-Yan
Zhang, Yan
Li, Jianxin
Cui, Hanbin
Chen, Xiaomin
Zhu, Zhiming
He, Hongbo
Mo, Xianming
Kennedy, Brian K.
Suh, Yousin
Zeng, Yi
Tian, Xiao-Li
Publication Title: 
PloS One

Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process.

Author(s): 
Campa, Daniele
de Rango, Francesco
Carrai, Maura
Crocco, Paolina
Montesanto, Alberto
Canzian, Federico
Rose, Giuseppina
Rizzato, Cosmeri
Passarino, Giuseppe
Barale, Roberto

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