Chromosomes, Human

Publication Title: 
Journal of Tissue Engineering and Regenerative Medicine

Tissue engineering involves the use of synthetic or natural materials as a scaffold to support the growth of replacement tissue or organs. The use of autologous cells to populate the scaffold avoids problems associated with rejection; however, a major limitation of this approach is the finite lifespan of primary cells in culture. This finite lifespan is due to the shortening of telomeres, short repetitive sequences of DNA located at the ends of eukaryotic chromosomes.

Author(s): 
Gamble, C. M.
Barton, P. A.
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: 
Journal of Human Genetics

Bivariate survival models with discretely distributed frailty based on the major gene concept and applied to the data on related individuals such as twins and sibs can be used to estimate the underlying hazard, the relative risk and the frequency of the longevity allele. To determine the position of the longevity gene, additional genetic markers data are needed. If the action of the longevity allele does not depend on its position in the genome, these two problems can be solved separately using a two-step procedure.

Author(s): 
Begun, Alexander
Publication Title: 
Psychoneuroendocrinology

We previously reported that psychological stress is linked to and possibly accelerates cellular aging, as reflected by lower PBMC telomerase and shortened telomeres. Psychological stress is a major risk factor for cardiovascular disease (CVD), with multiple behavioral and physiological mediators. Telomere shortness has been associated with CVD, but the relationship between low telomerase activity, a potential precursor to telomere shortening, and CVD risk factors has not been examined in humans.

Author(s): 
Epel, Elissa S.
Lin, Jue
Wilhelm, Frank H.
Wolkowitz, Owen M.
Cawthon, Richard
Adler, Nancy E.
Dolbier, Christyn
Mendes, Wendy B.
Blackburn, Elizabeth H.
Publication Title: 
Molecular Cell

Mammalian telomeres consist of tandem DNA repeats that bind protective protein factors collectively termed shelterins. Telomere disruption typically results in genome instability induced by telomere fusions. The mechanism of telomere fusion varies depending on the means of telomere disruption. Here, we investigate telomere fusions caused by overexpression of mutant telomerases that add mutated telomeric repeats, thereby compromising shelterin binding to telomeric termini.

Author(s): 
Stohr, Bradley A.
Xu, Lifeng
Blackburn, Elizabeth H.
Publication Title: 
Psychoneuroendocrinology

We previously reported that psychological stress is linked to and possibly accelerates cellular aging, as reflected by lower PBMC telomerase and shortened telomeres. Psychological stress is a major risk factor for cardiovascular disease (CVD), with multiple behavioral and physiological mediators. Telomere shortness has been associated with CVD, but the relationship between low telomerase activity, a potential precursor to telomere shortening, and CVD risk factors has not been examined in humans.

Author(s): 
Epel, Elissa S.
Lin, Jue
Wilhelm, Frank H.
Wolkowitz, Owen M.
Cawthon, Richard
Adler, Nancy E.
Dolbier, Christyn
Mendes, Wendy B.
Blackburn, Elizabeth H.
Publication Title: 
The American Journal of Psychiatry

OBJECTIVE: Some genome-wide scans and association studies for schizophrenia susceptibility genes have yielded significant positive findings, but there is disagreement between studies on their locations, and no mutation has yet been found in any gene. Since schizophrenia is a complex disorder, a study with sufficient power to detect a locus with a small or moderate gene effect is necessary.

Author(s): 
DeLisi, Lynn E.
Shaw, Sarah H.
Crow, Timothy J.
Shields, Gail
Smith, Angela B.
Larach, Veronica W.
Wellman, Nigel
Loftus, Josephine
Nanthakumar, Betsy
Razi, Kamran
Stewart, John
Comazzi, Margherita
Vita, Antonio
Heffner, Thomas
Sherrington, Robin
Publication Title: 
Molecular Endocrinology (Baltimore, Md.)

The estrogen receptor α (ERα) is a master regulator of gene expression and works along with cooperating transcription factors in mediating the actions of the hormone estradiol (E2) in ER-positive tissues and breast tumors. Here, we report that expression of paired-like homeodomain transcription factor (PITX1), a tumor suppressor and member of the homeobox family of transcription factors, is robustly up-regulated by E2 in several ERα-positive breast cancer cell lines via ERα-dependent interaction between the proximal promoter and an enhancer region 5' upstream of the PITX1 gene.

Author(s): 
Stender, Joshua D.
Stossi, Fabio
Funk, Cory C.
Charn, Tze Howe
Barnett, Daniel H.
Katzenellenbogen, Benita S.
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