Genome, Human

Publication Title: 
Blood

To obtain the large amount of T cells required for adoptive immunotherapy in a clinical setting, T-cell lifespan extension by human telomerase reverse transcriptase (hTERT) transduction is of particular interest. However, constitutive expression of hTERT is associated with malignant transformation and thus warrants a detailed evaluation of the safety of hTERT-transduced T cells before clinical application.

Author(s): 
Schreurs, Marco W. J.
Hermsen, Mario A. J. A.
Geltink, Ramon I. Klein
Scholten, Kirsten B. J.
Brink, Antoinette A. T. P.
Kueter, Esther W. M.
Tijssen, Marianne
Meijer, Chris J. L. M.
Ylstra, Bauke
Meijer, Gerrit A.
Hooijberg, Erik
Publication Title: 
BMC medical genetics

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS: We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families.

Author(s): 
Lunetta, Kathryn L.
D'Agostino, Ralph B.
Karasik, David
Benjamin, Emelia J.
Guo, Chao-Yu
Govindaraju, Raju
Kiel, Douglas P.
Kelly-Hayes, Margaret
Massaro, Joseph M.
Pencina, Michael J.
Seshadri, Sudha
Murabito, Joanne M.
Publication Title: 
BMC bioinformatics

BACKGROUND: Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge.

Author(s): 
Gillis, Jesse
Pavlidis, Paul
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Substantial evidence supports the familial aggregation of exceptional longevity. The existence of rare families demonstrating clustering for this phenotype suggests that a genetic etiology may be an important component. Previous attempts at localizing loci predisposing for exceptional longevity have been limited to association studies of candidate gene polymorphisms. In this study, a genome-wide scan for such predisposing loci was conducted by using 308 individuals belonging to 137 sibships demonstrating exceptional longevity.

Author(s): 
Puca, A. A.
Daly, M. J.
Brewster, S. J.
Matise, T. C.
Barrett, J.
Shea-Drinkwater, M.
Kang, S.
Joyce, E.
Nicoli, J.
Benson, E.
Kunkel, L. M.
Perls, T.
Publication Title: 
PloS One

BACKGROUND: Human lifespan is approximately 25% heritable, and genetic factors may be particularly important for achieving exceptional longevity. Accordingly, siblings of centenarians have a dramatically higher probability of reaching extreme old age than the general population. METHODOLOGY/PRINCIPAL FINDINGS: To map the loci conferring a survival advantage, we performed the second genomewide linkage scan on human longevity and the first using a high-density marker panel of single nucleotide polymorphisms.

Author(s): 
Boyden, Steven E.
Kunkel, Louis M.
Publication Title: 
PloS One

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls.

Author(s): 
Sebastiani, Paola
Solovieff, Nadia
Dewan, Andrew T.
Walsh, Kyle M.
Puca, Annibale
Hartley, Stephen W.
Melista, Efthymia
Andersen, Stacy
Dworkis, Daniel A.
Wilk, Jemma B.
Myers, Richard H.
Steinberg, Martin H.
Montano, Monty
Baldwin, Clinton T.
Hoh, Josephine
Perls, Thomas T.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Genetic factors clearly contribute to exceptional longevity and healthy aging in humans, yet the identification of the underlying genes remains a challenge. Longevity is a complex phenotype with modest heritability. Age-related phenotypes with higher heritability may have greater success in gene discovery. Candidate gene and genome-wide association studies (GWAS) for longevity have had only limited success to date.

Author(s): 
Murabito, Joanne M.
Yuan, Rong
Lunetta, Kathryn L.
Publication Title: 
PLoS genetics

Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes.

Author(s): 
Bell, Jordana T.
Tsai, Pei-Chien
Yang, Tsun-Po
Pidsley, Ruth
Nisbet, James
Glass, Daniel
Mangino, Massimo
Zhai, Guangju
Zhang, Feng
Valdes, Ana
Shin, So-Youn
Dempster, Emma L.
Murray, Robin M.
Grundberg, Elin
Hedman, Asa K.
Nica, Alexandra
Small, Kerrin S.
MuTHER Consortium
Dermitzakis, Emmanouil T.
McCarthy, Mark I.
Mill, Jonathan
Spector, Tim D.
Deloukas, Panos
Publication Title: 
Aging Cell

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project.

Author(s): 
Beekman, Marian
BlanchÈ, HÈlËne
Perola, Markus
Hervonen, Anti
Bezrukov, Vladyslav
Sikora, Ewa
Flachsbart, Friederike
Christiansen, Lene
de Craen, Anton J. M.
Kirkwood, Tom B. L.
Rea, Irene Maeve
Poulain, Michel
Robine, Jean-Marie
Valensin, Silvana
Stazi, Maria Antonietta
Passarino, Giuseppe
Deiana, Luca
Gonos, Efstathios S.
Paternoster, Lavinia
S¯rensen, Thorkild I. A.
Tan, Qihua
Helmer, Quinta
van den Akker, Erik B.
Deelen, Joris
Martella, Francesca
Cordell, Heather J.
Ayers, Kristin L.
Vaupel, James W.
Tˆrnwall, Outi
Johnson, Thomas E.
Schreiber, Stefan
Lathrop, Mark
Skytthe, Axel
Westendorp, Rudi G. J.
Christensen, Kaare
Gampe, Jutta
Nebel, Almut
Houwing-Duistermaat, Jeanine J.
Slagboom, Pieternella Eline
Franceschi, Claudio
GEHA consortium
Publication Title: 
Trends in genetics: TIG

Physicochemical properties preclude ideal biomolecules and perfect biological functions. This inherent imperfectness leads to the generation of damage by every biological process, at all levels, from small molecules to cells. The damage is too numerous to be repaired, is partially invisible to natural selection, and manifests as aging. I propose that the inherent imperfectness of biological systems is the true root of the aging process. Because each biomolecule generates specific forms of damage, the cumulative damage is largely non-random and is indirectly encoded in the genome.

Author(s): 
Gladyshev, Vadim N.

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