Telomerase Biology Associations Offer Keys to Cancer and Aging Therapeutics.

Background: Although telomerase has potential for age-related disease intervention, the overexpression of telomerase in about 90% of cancers, and in HIV virus reservoirs, cautions against se in anti-aging telomerase therapeutics. While multiple reviews document the canonical function of telomerase for maintenance of telomeres, as well as an increasing numbers of reviews that reveal new non-canonical functions of telomerase, there was no systematic review that focuses on the array of associates of the subunit of Telomerase Reverse transcriptase protein (TERT) as pieces of the puzzle to assemble a picture of the how specific TERT complexes uniquely impact aging and age-related diseases and more can be expected.

Methods: A structured search of bibliographic data on TERT complexes was undertaken using databases from the National Center for Biotechnology Information Pubmed with extensive access to biomedical and genomic information in order to obtain a unique documented and cited overview of TERT complexes that may uniquely impact aging and age-related diseases.

Alternative strategy for Alzheimer's disease: stress response triggers.

Stress resistance capacity is a hallmark of longevity protection and survival throughout the plant and animal kingdoms. Latent pathway activation of protective cascades, triggered by environmental challenges to tolerate heat, oxygen deprivation, reactive oxygen species (ROS), diet restriction, and exercise provides tolerance to these stresses. Age-related changes and disease vulnerability mark an increase in damage, like damage induced by environmental challenges.

Acute therapeutic use of 5-aminoimidazole-4-carboxamide ribonucleoside extends survival interval in response to severe hemorrhagic shock.

This study tests the hypothesis that pretreatment and/or posttreatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an inducer of adenosine monophosphate-activated protein, will extend the golden hour of survival time in rats subjected to severe hemorrhagic shock in the absence of available fluid resuscitation. Three days before hemorrhage, at 24-h intervals, animals were given three i.p.

delta2 opioid receptor agonist facilitates mean arterial pressure recovery after hemorrhage in conscious rats.

delta opioid receptor agonists exert potent hemodynamic effects under ischemic conditions. This study was designed to assess the cardiovascular effects of Deltorphin-D(variant) (Delt-D(var)), a selective delta(2) opioid receptor agonist, in conscious, freely moving male rats during the posthemorrhage, recompensatory phase of a hemorrhagic trauma. Rats were fitted with femoral arterial and venous catheters for measurements of mean arterial pressure (MAP), heart rate (HR), and intravenous (i.

Supplemental melatonin increases clonal lifespan in the protozoan Paramecium tetraurelia.

The hypothesis that melatonin supplementation can increase the lifespan of a single-celled organism was tested by the administration of melatonin to the ciliated protozoan Paramecium tetraurelia. Melatonin supplementation in dim red light at a dose of 0.043 mM (10 mg/L) of nutrient media (bacterized Cerophyl) per day, followed by incubation for 23 hr in darkness, increased the mean clonal lifespan of Paramecium tetraurelia in days by percentages ranging from 20.

Longevity in the protozoa.

In ciliates there are examples of cells which have different proliferation potential in the macronucleus. Those species with limited macronuclear proliferation potential require sex to activate the reserve nucleus. In terms of the capital investment theory, some ciliates invested in their spare nucleus without loss of their original potential, while others accumulated debts and needed the reserve account to maintain life.

Bioassay of environmental nickel dusts in a particle feeding ciliate.

The ciliated protozoan Paramecium was used to quantitate cytotoxic and genotoxic effects of nickel particles. The biological response of these eukaryotic cells to pure nickel powder and iron-nickel powder was assayed and compared to the effect of the inorganic carcinogen nickel subsulfide. Cytotoxicity was determined by the percent survival of treated cells.

Effects of an extremely low frequency electromagnetic field on the cell division rate and plasma membrane of Paramecium tetraurelia.

The eukaryotic protozoan, Paramecium, was examined as a model for effects of pulsated electromagnetic fields (PEMF) on cells. A 72-Hz PEMF similar to fields employed clinically increased cell division rates in Paramecium by 8.5%.

Bioassay of genotoxic effects of environmental particles in a feeding ciliate.

The ciliated protozoan, Paramecium, can be used to quantitate cytotoxic and genotoxic effects of ingested complex environmental particles. Cytotoxicity is quantitated by the increased proportion of treated versus control cells which do not retain their capacity for normal cell replication. Genotoxic effects are assessed by the increased fraction of nonviable offspring from treated versus control parent cells after the self-fertilization process of autogamy.

Nucleolar changes in aging and autogamous Paramecium tetraurelia.

A significant loss in nucleolar volume density (proportion of nuclear volume occupied by nucleoli) occurs in the macronucleus as clonal age increases, which suggests an age-correlated loss of ribosomal RNA synthesizing capacity. In the macronuclear fragments of cells undergoing autogamy, however, a significant gain in nucleolar volume density takes place.

Mutagenicity of fly ash particles in Paramecium.

Paramecium, a protozoan that ingests nonnutritive particulate matter, was used to determine the mutagenicity of fly ash. Heat treatment inactivated mutagens that require metabolic conversion to their active form but did not destroy all mutagenicity. Extraction of particles with hydrochloric acid, but not dimethyl sulfoxide, removed detectable mutagenic activity.

Mutagenicity of coal fly ash: a new bioassay for mutagenic potential in a particle feeding ciliate.

The use of the established mutagenesis assay in Paramecium as a prescreen for hazardous environmental particles is described. Since these protozoans ingest particles of the size respired by animals and man, the biological effects of the respirable fraction of fly ash particles were monitored in particle-feeding eukaryotic cells. Fly ash from coal combustion was utilized for these studies and was found to be mutagenic.

Malic dehydrogenase locus of Paramecium tetraurelia.

A search was undertaken for naturally occurring genetic markers for use in clonal aging studies of Paramecium tetraurelia. Clonal age is defined as the number of cell divisions since the last sexual process. Autogamy (self-fertilization) is a sexual process which can occur in aging lines, resulting in homozygosity and initiation of the next generation.

DNA repair and longevity assurance in Paramecium tetraurelia.

At given doses and clonal ages, ultraviolet irradiation-induced DNA damage reduced clonal life-span, but when followed by photoreactivation, extension of clonal life-span was observed. If photoreactivation preceded the ultraviolet treatment, no significant beneficial effect was detected. Because studies of others have shown that photoreactivation repair monomerizes the ultraviolet-induced cyclobutane dimers in DNA, but does not affect the other photoproducts, these results indicate that DNA damage can influence the duration of clonal life-span unless that damage is repaired.

Age-correlated changes in expression of micronuclear damage and repair in Paramecium tetraurelia.

In Paramecium, age is defined as the number of mitotic divisions which have elapsed since the previous cross-fertilization (conjugation) or self-fertilization (autogamy). As the mitotic interval between fertilizations increases, the percentage of nonviable progeny clones increases. In the current study, resolution of conflicting previous reports on the pattern of increase of death and reduced viability in progeny from aging parent cells is found.

Loss of endocytic capacity in aging Paramecium. The importance of cytoplasmic organelles.

Aged cells have significantly fewer food vacuoles and ingest fewer bacteria than young cells. Loss of food vacuoles was explained by a decreasing difference in the food vacuole formation and excretion rates; the formation rate declined more rapidly than the excretion rate, approaching equivalence at 160 fissions, when the proportion of cells with no food vacuoles, in the presence of excess food, abruptly increased. A model for cellular aging is presented in which control of organelle numbers and cyclical interactions between the nucleus and cytoplasm may be of critical importance.

Calendar life-span versus fission life-span of Paramecium aurelia.

The hypothesis that paramecia use fissions, not days, to measure length of cell life-span was investigated. Parallel cell lines were grown at 27 C and at 24 C. The daily fission rate of the cells at 24 C was lower than at 27 C.

Changes in the DNA synthesis pattern of paramecium with increased clonal age and interfission time.

The clonal age in paramecia refers to the total number of vegetative divisions a clone has undergone since its origin at autogamy (self-fertilization). As clonal age increases, the interfission time usually increases. The DNA synthesis pattern of cells of different ages was compared by autoradiographic analysis of the DNA synthesis of synchronized cells at various time intervals during the cell cycle (from one division to the next).