Cellular Senescence Mechanisms Independent of Telomere Shortening and Telomerase: Other Barriers to Cell Immortalization and Carcinogenesis

Interestingness: 4

By Izumi Horikawa, Toshio Yawata, and J Carl Barrett in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 373-382, doi:10.1089/rej.1.2000.3.373.)

 Not all cells given telomerase escape senescence and cells with active telomerase can be made to senesce in lots of ways. The p16^INK4A/RB pathway can trigger senescence as well as the p14^ARF/MDM2/p53 pathway. p53 is probably related to telomeres but other parts probably aren't. By introducing single chromosomes into immortal cancer cell-lines and making them senesce, they infer the existence of other independent pathways of senescence. The mechanisms that trigger senescence are cell-type dependent.

Interesting factoid: mouse cells senesce after much fewer replications (10-20 vs 50-80) even though much longer telomeres.

Telomeres, Telomerase, and Premature Aging

Interestingness: 4

By Corrin V Wallis and Richard GA Faragher in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000.

Nice summary of telomeres, telomerase and also about the relations of telomeres, Werner's syndrome, Hutchinson-Gilford progeria syndrome and aging. Quite a few details of the proteins involved that I wasn't aware of and that I'll forget about in the next hour.

Review of the Gerontology Literature in Volume 3, Issue 3

To be clear, this is the summary of the reviews, not the reviews themselves. Reviews by Barry Flanary

Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase, by Ouellette MM, Liao M, Herbert BS, Johnson M, Holt SE, Liss HS, Shay JW, Wright WE, in Biol Chem 2000;275:10072-10076

I don't think I understand this result. They transfected cells in-vitro with telomerase reverse transcriptase. Those cells had decreasing telomerase activity as they got older, and then lived longer (their number of doublings went from 60-70 to 250-400). Their telomeres shortened from the 1.5kb-10kb range to the 1.5kb-6kb range. Some theorising that the telomerase was preferentially taken up by the shorter telomeres, thus keeping it from hitting the criticial length at which the cells would go senescent.


Cytotoxic T cell immunity against telomerase reverse transcriptase in humans, by Minev B, Hipp J, Firat H, Schmidt JD, Langlade-Demoyen P, Zanetti M, in Proc Nati Acad Sci USA 2000;97:4796-4801.

Experimenting with using the immune system that naturally attacks hTERT to hammer tumor cells, since they produce hTERT. T cells from prostate cancer patient hammered some tumour lines.


Extension of cell life-span and telomere length in animals cloned from senescent somatic cells, by Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, Mak J, Schertzer M, Chavez EA, Sawyer N, Lansdorp PM, West MD, in Science 2000;288:665-669.


Cloning of cows from a 45 day old fetus. Resulting cells extracted from fibroblasts had higher replicative capacity and telomere lengths than controls. I'm sure we know much more about cloning now, so this has probably been overturned and back a hundred times.

Glucagon-Like Peptide 1 (GLP-1) in Diabetes and Aging

By David D'Alessio in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, 2000.

Interestingness: 2

I'd never heard of GLP-1, but it seems to accentuate the glucose-lowering effect of insulin, by including but maybe not limiting to, increasing insulin secretion. Maybe also acts as a satiety marker. GLP-1 is synthesised in the intestines. Glucose eaten has much higher effect on increasing insulin than glucose injected.  Lots of problems in studies caused by mixing detection of active and inactive form of the peptide.

Giving up and Adrenal Andropause and Aging

Writing even the half-arsed summaries takes too long, so I'm giving up on those.  From now on, it will be most likely down to an interestingness score, tags and a one line summary, mainly for me to keep track of them.  Also, no more abstract cut-n-pasting, since it probably is not as legit as I thought it was before.


So, Adrenal Andropause and Aging, by Samuel SC Yen,  in the Journal of Anti-Aging Medicine, Volume 3, Issue 3, 2000.

Interestingness: 2

Nice review on cortisol changes with aging and DHEA/DHEA-S changes with aging, and how they diverge, cortisol going up and DHEA-S going down, post adrenopause (30s), even though they are both produced by the adrenal glands. Mentions possible link to immune system (DHEA-S inversely correlated to IL-6)