In SENS4 (Cambridge, Thursday Sept 3rd) Stephen Spindler will talk about
Screening potential longevity therapeutics using rodent lifespan assays
http://www.sens.org/...n...ract&ID=163In this presentation we will describe screening studies of potential longevity therapeutics using mouse longevity assays that avoid these and other artifacts. Among the agents tested alone and together in our 60 treatment groups are compounds that enhance somatostatin, insulin, or dopamine D(2)/D(3) receptor signaling; reduced androgen, thyroid, angiotensin II, or β-adrenergic receptor signaling; inhibit advanced glycation end product, HMG CoA reductase, acetyl CoA reductase, fatty acid synthase, MAO-B, mTOR, dipeptidyl peptidase 4, or α-glucosidase activity; or induce telomerase or SirT1 activity.
He has done MANY lifespan tests in mice, won the MPrize; from pubmed readings he appearently believes in CR and GH insufiiciency and gene expression array - related approaches to first quest for potential life extension drugs:
Comment on: The case for prioritizing research on late-onset life-extension interventions in mammals.Screening candidate longevity therapeutics using gene-expression arrays.The video is here:
http://75.126.26.34/...p;g2_itemId=218(the second half of the video corresponds to this thread) and here is the list of things his lab is currently testing on the lifespan of 1 year old mice, with a particular care to avoid caloric-restriction effects and to link the experiments with diseases and mechanisms:
Controls
- 296 negative control group
- 20% CR positive control group
- 40% CR positive control group
CR/dwarf-like (trying to chemically reproduce the effect of caloric restriction on major signaling systems)
- Sandostatin injection that lowers IGF1 levels, and IGF1 levels are measured: Sandostatin LAR depot (Somatostatin, super-agonist)
- Bromocripine lowers growth hormone levels as well as prolactin levels: (Dopamine D????) receptor agonist
- Cyproterone acetate lowers androgens (Androgen receptor antagonist)
- Iodine free diet with methymazole & perchlorate: makes hyperthyroid
- Bromocriprine, cyproterone, numidazole, potassium perchlorate
- OAA (increase NAD+NAOH)
- resveratrol
Cardioprotection- Simvastatin (Statin)
- Rampril (ACE inhibitor) & Simvastatin (statin)
- Carderatan I, Angiotensin II receptor antagonist,
Rampril, Simvastatin & aspirin
- Netoprovol (beta1 adrenergic receptor blocker)
- Nethovel (beta adrenergic receptor blocker)
because such blockers extend lifespan
- Lovata (omega-3 fatty acids): "fish oil" in essence
- KHOH
- Niopiric acid (reduces LDL-C, HDL-Cl, liporetdnfi)
Anticancer- Everolimus (Orally available rapamycin defuntive, mTOR inhibitor)
- Green tea extract (FAS inhibitor)
- Green tea extract, Black tea extract, Morin
(O.O5% in diet) & Tricloman (0.1% in diet) (FAS inhibitors)
Insulin sensitivity- Metformin (2 doses)
- Resveratrol & 20% CR
- Stagiptin (cypristicylseptidase 4 inhibitor, enhances insulin secretion)
- Vigobone (alpha-glucosidase inhibitor, lowers post-prandial blood glucose)
Inflammation- NDGA (4 doses)
- Curcumin (microencapsulated, 2 doses)
Miscellaneous- Rasagiline (Orally available degrol)
- TA-65 (Telomerase induction; 2 doses)
- Creatinine
- Juvenon
- SAMe
- CoQ10 (Coenzyme in Caphom)
- Carnitine (taty acids uptake into mitochondria)
- Glutathione (in liposomes)
note: if someone can explain those choices for laymen, go ahead, that would be great
Also, here is the list of things the NIA is testing in mice, and the dose and mouse-age at start:
http://www.nia.nih.g...dsInTesting.htmCohort 1:
Aspirin - 20 ppm - 4 months
NFP - 200 ppm - 4 months
NDGA - 2,500 ppm - 9 months
4-OH-PBN - 315 ppm - 4 months
Cohort 2:CAPE - 30 ppm - 4 months
CAPE - 300 ppm - 4 months
Enalapril Maleate - 120 ppm - 4 months
Rapamycin - 14 ppm - 20 month
Cohort 3: Rapamycin - 14 ppm - 9 months
Simvastatin - 12 ppm - 10 months
Simvastatin - 120 ppm - 10 months
Resveratrol - 300 ppm - 12 months
Resveratrol - 1200 ppm - 12 months
Cohort 4: Resveratrol - 300 ppm - 4 months
Oxaloacetic acid - 2200 ppm - 4 months
Green tea extract - 2000 ppm - 4 months
Curcumin - 2000 ppm - 4 months
Medium Chain Triglyceride Oil - 60000 ppm - 4 months
Cohort 5:17α-Estradiol - 4.8 ppm - 10 months
Methylene Blue - 28 ppm - 4 months
Acarbose - 1000 ppm - 4 months
Rapamycin_LoPhase II - 4.7 ppm - 9 months
Rapamycin_MidPhase II - 14 ppm - 9 months
Rapamycin_HiPhase II - 42 ppm - 9 months
(Compound - Concentration in food - Age at treatment initiation)
I interpret that:
- schedule: they are done with cohorts 1 and 2, and that they are starting the lifespan tests of cohort 3. Based on when the results with aspirin were published (cohort 1) the results with
Methylene blue would be published by mid/late 2012 (Methylene blue is/was the first thing we have/had in mind for MPrize at home)
- rapamycin: the rapamycin tests are done under a quasi-sterile unvironment (SPF)? (a 'normal' environment would be of interest because rapamycin is an immunosuppressant).
If you can confirm/correct me, please go ahead. Also if you can easily explain why those compounds and doses are interesting, that would be great. Note: the ITP is currently asking for new things to test...
note: this post is similar to what I wrote in MF:
http://www.mfoundati...read.php?p=8327
Edited by Michael, 25 December 2009 - 02:21 PM.