Prevalence of Telomerase in Coronary Artery Atherosclerosis

Summary: Telomerase detected in atherosclerotic plaque tissue, likely to be related to restenosis.

Interestingness: 3

Paper by Madhu Gupta, Marie R Shogreen, Gregory A Braden, Wain L White and David C Sane in the Journal of Anti-Aging Medicine, Volume 3, Issue 1, Spring 2000.


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They measured the presence of telomerase in the bits cut out of 23 people that had directional coronary atherectomy (DCA). The bits cut out are blockages of the coronary artery and the DCA cuts it out. They correlated the tissues in which they detected telomerase with those that had restenosis, which is when the blockage/narrowing of the artery reappears.

They detected telomerase in 8 out of the 23 total, in 5 out of the 7 people who later developed restenosis, and on 2 out of the 10 who didn't (p < 0.05). Results were inconclusive for restenosis in the other 6. There was no correlation between what the people had come in for and the presence of telomerase.

They mention that atherosclerotic plaques have a monoclonal population of smooth muscle cells, but I don't know what other type you could have inside one person. They offer three explanations for the 35% detection rate of telomerase, that is, how come it's not 100%:

• that the tissue is maintaining its telomeres by means other than telomeres
• that the tissue is senescent or closer to senescence, with some evidence coming from studies on replicative capacity of muscle cells from plaque-derived tissue compared to healthy arteries. The presence of telomerase would probably be induced by cells having replicated beyond the normal senescent stage by a viral infection or broken tumor-suppressors, and that this would activate telomerase. These cells would then be better able to cause restenosis. I have no idea how much reality there is to that idea of telomerase reactivation.
• that there was no telomerase in the smooth-muscle cells at all, and instead the telomerase was detected from other cells in the tissue cut out. This could be from vascular stem cells, or from non-related cells like endothelial cells, lymphocytes or macrophages.

They also mention that the telomerase could be driving the hyperplasia not by replication but by stopping apoptosis.

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Abstract follows:

Telomerase is an essential enzyme for maintaining the telomeres of chromosomes and thereby enhancing the sustained replication of cells. Because atherosclerosis and restenosis are characterized by cellular proliferation, we determined whether telomerase enzyme activity was present in coronary artery tissue from 23 patients undergoing directional coronary atherectomy. Telomerase activity was determined from detergent lysates of the atherectomy tissue using an enzyme-linked immunoadsorbent assay (ELISA)-based modification of the Telomere Repeat Amplification Protocol. The presence of telomerase activity was correlated with the occurrence of coronary artery restenosis. Eight of the 23 samples (35%) were positive for telomerase. Seventeen of the 23 patients had adequate clinical follow-up to judge restenosis status. Of these, 7 had restenosis and 5 of these 7 had detectable telomerase. Of the 10 patients without restenosis, 8 were telomerase negative (p <= 0.05). We have shown, for the first time, that telomerase is found in 35% of atherosclerotic tissues. There was a strong trend toward an association between telomerase presence and restenosis in patients for whom follow-up data were available. The presence of telomerase in atherosclerotic tissue may enable a robust, sustained cellular proliferation in response to vascular injury that culminates in restenosis.

Rest of volume 2, Issue 4

The rest of issue 4 of 1999 consists of:

A review of a book called Essentials of Clinical Geriatrics, 4th edition, edited by Robert L Kane, Joseph G Ouslander and
Itamar B Abrass. "Concise" 621 pages of differences between geriatric and standard medicine.


Seven article reviews by L Stephen Coles:

• Gene expression profile of aging and its retardation by caloric restriction, by Cheoi-Koo Lee, Roger G Klopp, Richard Weindruch and Tomas A Prolla, in Science. Analysis of what genes change in muscle cells in old mice compared to young mice compared to old calorie restricted mice using a gene chip of 6000 genes. Lots of changes, with caloric restriction reducing the changes by 84%. L Stephen Coles thought this was a very important paper.
  
• Can human aging be postponed?, by Michael R Rose, in Scientific American. Some pop-sci sounding piece.
• Designer genomes, by Karen Hopkin, in Scientific American. Another pop-sci sounding piece about creating cells from scratch. Mentions Venter's knock out method of finding the minimal set. I didn't know he had been going at it that long.
• Telomeres and telomerase in cancer, by Christopher M Counter, in Science and Medicine. Supposedly nice graphics.
• Aging: The price of evolutionary success, by Robert F Rosenberger, in Science Spectra: The international magazine of contemporary scientific thought. About germ vs soma.
• The hunt for the youth pill: From cell-immortalizing drugs to cloned organs, biotech finds new ways to fight against time's toll, by David Stipp, in Fortune Magazine.
• Never say die, by Lisa Leff, in the Los Angeles Magazine.

Season of Birth and Human Longevity

Summary: Adult women over thirty live three years longer if they were born in May or December, rather than in August.

Interestingness: 2

Paper by Leonid A Gavrilov and Natalia S Gavrilova in the Journal of Anti-Aging Medicine, Volume 2, Issue 4, Winter 1999.

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Short two-page paper analysing a subset of the same data they used for their longevity vs fertility paper, ie European aristocratic families. In this case, they analysed a lot of variables until they found one that correlated with longevity.

On the relevant subsample of 4911 women, adult women over 30 born between 1800 and 1880 lived shortest if they were born in August and longest if they were born in May with the difference at about three and a half years. This is after correcting for a whole heap of variables that have nothing to do with month of birth but are related to longevity: year of birth, maternal and paternal life spans, age of parents at birth, birth order, nationality, whether the death was violent, loss of either or both parents before age twenty.

They have a graph and it doesn't look good to me. The only reasons I can think of, and that they propose, for the effect would be availability of vitamins (or calories but they are unlikely to be a problem for this group since they were all from aristocratic families) at specific points in the pregnancy or early life, but the graph is very noisy and it mostly jumps up and down. For example, the difference between July and August births is two and a bit years, and between August and September the difference is about a year and a half, with August at the minimum. The other bad months are February and March, on the other side of the year, with women born then living about a year longer than those in August. If the effect is real, then the critical periods during pregnancy must be very short.

I'm not buying any of it until it gets replicated.
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Adaptive Response to Swimming Exercise: Antioxidant Systems and Lipid Peroxidation

Summary: Anti-oxidant enzyme concentrations go up in the blood of rats that go swimming

Interestingness: 1

Paper by M Cesquini, MA Torsoni and SH Ogo in the Journal of Anti-Aging Medicine, Volume 2, Issue 4, Winter 1999.

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The abstract has everything covered. Note that these tests were on three groups of four rats each. Also, catalase was down on the endurance-trained group.
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Abstract follows:

Enzymatic and nonenzymatic antioxidants play an essential role in protecting tissues from oxidative damage during exercise. The present study investigated the levels of glutathione and antioxidant enzyme systems in the blood of unexercised and exercised (one bout of exhaustive swimming and adapted to swimming endurance training) rats. The hemoglobin concentration, hematocrit, and extent of oxidative injury to red blood cell (RBC) membranes were examined in the above groups of rats. The concentration of reduced glutathione (GSH) in the blood of exercised rats was about 30% higher than in the resting controls (0.40 Å [±] 0.12 GSH/Hb tetramer). Glutathione peroxidase (1.83 Å 0.24 X 102 IU/g Hb), glutathione reductase (1.73 Å 0.44 IU/g Hb), and Superoxide dismutase activities were significantly higher in both groups of exercised rats, whereas catalase activity (8.32 Å 1.04 X 104 IU/g Hb) was similar in the exercised and control animals. The hemoglobin concentration (11.8 g Hb/dL) and hematocrit (39.4%) increased with swimming exercise. Although lipid peroxidation is known to occur following physical exercise, the increased activity of the antioxidant enzymes and cell GSH levels in the present study were able to prevent lipid peroxidation of the RBC membrane. As a result, there was no significant variation in the plasma malondialdehyde levels among the three groups of rats. The redox capacity of the blood may have an important role in the organism in general since the redox status can be transferred across the RBC plasma membrane to other tissues. Exercise training is therefore beneficial to general health and protects cells against deleterious effects of reactive oxygen species produced during physical effort.