Lung

Inclusion of vitamin E (DL-alpha-tocopherol) in the culture medium for human diploid cells greatly prolongs their in vitro lifespan. The addition of 100 mug of DL-alpha-tocopherol per ml of medium has allowed us to culture WI-38 cells for more than 100 population doublings to date. (These cells normally have an in vitro lifespan of 50 +/- 10 population doublings.) Cells at the 100th population doubling have a normal diploid karyotype, appear to behave in all other respects like young WI-38 cells, and are still actively dividing.

It has been shown that human diploid cells from various donor ages can be arrested in an essentially nonmitotic state by reducing the serum concentration of the incubation medium from 10 to 0.5 percent. Cells incubated at this serum level maintained the population distribution that was present when the cells reached confluency. The population, which has 90 percent of the cells in the G1 phase of the division cycle, was not static and exhibited a low level of mitotic activity with prolonged interdivision times.

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined.

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

We report the natural history, the clinical, radiological, echocardiographic and hemodynamic pattern of a living sixty-three year old man with tetralogy of Fallot and cyanosis since birth. We discuss the possible circulatory adaptations which allowed exceptional survival up to the seventh decade: it is the sixth case reported in the literature.

BACKGROUND: Identification of gene variants that contribute to exceptional survival may provide critical biologic information that informs optimal health across the life span. METHODS: As part of phenotype development efforts for the Long Life Family Study, endophenotypes that represent exceptional survival were identified and heritability estimates were calculated. Principal components (PCs) analysis was carried out using 28 physiologic measurements from five trait domains (cardiovascular, cognition, physical function, pulmonary, and metabolic).

Cell adhesion molecule 1 (CADM1), expressed by human lung mast cells (HLMCs), mediates their adhesion to airway smooth muscle (ASM), and contributes to ASM-dependent HLMC proliferation and survival. CADM1 is expressed in alternatively spliced isoforms, but those present in HLMCs and their function are not known. We cloned three functional and one cryptic non-functional isoform with alternative splicing between exons 7/11 and 1/2, respectively, from HLMCs and human MC lines (HMC-1 and LAD2).

The increased longevity afforded by combination antiretroviral therapy in developed countries has led to an increased concern regarding senescence-related diseases in patients with human immunodeficiency virus (HIV) infection. Previous epidemiologic analyses have demonstrated an increased risk of chronic obstructive pulmonary disease, as well as a significant burden of respiratory symptoms in HIV-infected patients. We performed the St.

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

PURPOSE: To test ribozymes targeting mouse telomerase RNA (mTER) for suppression of the progression of B16-F10 murine melanoma metastases in vivo. EXPERIMENTAL DESIGN: Hammerhead ribozymes were designed to target mTER. The ribozyme sequences were cloned into a plasmid expression vector containing EBV genomic elements that substantially prolong expression of genes delivered in vivo. The activity of various antitelomerase ribozymes or control constructs was examined after i.v. injection of cationic liposome:DNA complexes containing control or ribozyme constructs.