Publication Title: 
Experimental Cell Research

Normal human diploid cells, TIG-1, ceased to proliferate at about the 62 population doubling level (PDL). Transformed clones isolated from TIG-1 cells infected with wtSV40 and those with tsA900 SV40 cultured at 34 degrees C were subcultured up to about 80 PDL. When the culture temperature of tsA SV40-transformed cells was shifted from 34 to 39.5 degrees C at 51 PDL, the growth curve of these transformed cells changed to that of normal young cells.

Ide, T.
Tsuji, Y.
Nakashima, T.
Ishibashi, S.
Publication Title: 
Free Radical Biology & Medicine

Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.

Elia, A. J.
Parkes, T. L.
Kirby, K.
St George-Hyslop, P.
Boulianne, G. L.
Phillips, J. P.
Hilliker, A. J.
Publication Title: 

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.

Herndon, Laura A.
Schmeissner, Peter J.
Dudaronek, Justyna M.
Brown, Paula A.
Listner, Kristin M.
Sakano, Yuko
Paupard, Marie C.
Hall, David H.
Driscoll, Monica
Publication Title: 
Aging Cell

A major challenge in current research into aging using model organisms is to establish whether different treatments resulting in slowed aging involve common or distinct mechanisms. Such treatments include gene mutation, dietary restriction (DR), and manipulation of reproduction, gonadal signals and temperature. The principal method used to determine whether these treatments act through common mechanisms is to compare the magnitude of the effect on aging of each treatment separately with that when two are applied simultaneously.

Gems, David
Pletcher, Scott
Partridge, Linda
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates.

Nguyen, Trent
Hamby, Aaron
Massa, Stephen M.
Publication Title: 
Nature Cell Biology

The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. The mammalian homologue of Sir2 (SirT1) regulates p53, NF-kappaB and Forkhead transcription factors, and is implicated in stress response. This report shows that the cell-cycle and apoptosis regulator E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop.

Wang, Chuangui
Chen, Lihong
Hou, Xinghua
Li, Zhenyu
Kabra, Neha
Ma, Yihong
Nemoto, Shino
Finkel, Toren
Gu, Wei
Cress, W. Douglas
Chen, Jiandong
Publication Title: 
Aging Cell

Dyskeratosis congenita (DC), an inherited bone marrow failure syndrome, is caused by defects in telomerase. Somatic cells from DC patients have shortened telomeres and clinical symptoms are most pronounced in organs with a high cell turnover, including those involved in hematopoiesis and skin function. We previously identified an autosomal dominant (AD) form of DC that is caused by mutations in the telomerase RNA component (TER).

Westin, Erik R.
Chavez, Elizabeth
Lee, Kimberly M.
Gourronc, Francoise A.
Riley, Soraya
Lansdorp, Peter M.
Goldman, Frederick D.
Klingelhutz, Aloysius J.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Rather than being a passive, haphazard process of wear and tear, lifespan can be modulated actively by components of the insulin/insulin-like growth factor I (IGFI) pathway in laboratory animals. Complete or partial loss-of-function mutations in genes encoding components of the insulin/IGFI pathway result in extension of life span in yeasts, worms, flies, and mice. This remarkable conservation throughout evolution suggests that altered signaling in this pathway may also influence human lifespan.

Suh, Yousin
Atzmon, Gil
Cho, Mi-Ook
Hwang, David
Liu, Bingrong
Leahy, Daniel J.
Barzilai, Nir
Cohen, Pinchas
Publication Title: 
PLoS genetics

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases.

Collins, James J.
Evason, Kimberley
Pickett, Christopher L.
Schneider, Daniel L.
Kornfeld, Kerry
Publication Title: 
Experimental Dermatology

Dyskeratosis congenita (DC) is characterized by the triad of reticulate skin pigmentation, nail dystrophy and leukoplakia. Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients. DC is caused by mutations in genes encoding for telomerase complex factors. Although there is an association of epidermal abnormalities with DC, epidermal cells from DC donors have not been previously characterized.

Gourronc, Francoise A.
Robertson, mckaylee M.
Herrig, Annie K.
Lansdorp, Peter M.
Goldman, Frederick D.
Klingelhutz, Aloysius J.


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