lobby for lifespan tests when toxicity tes...
AgeVivo 01 Jul 2009
TODAY
- Do you know how long standard lab mice live? ... about 2 years and a half on average; most die between 2 and 3 years old (similar with rats)
- Do you know how long toxicity/carcinogesis tests last in rodents? ... 2 years; probably because old age did not interest people when toxicity tests where initially designed
- Do you see the trouble? ... Because of these 6-12 months of test lacking,
for most drugs and chemicals that are around us* we have no idea of their impact on lifespan!!!
- Could it be different? ... Yes, technically it seems easy: simply don't stop toxicity/carcinogenesis tests so early. Everything is already in place, simply don't stop the experiment (at least when no severe drawbacks are found after 2 years; that's such a shame!)
- How to make it change? ... I'm not sure yet. Perhaps first contacting the NTP. Perhaps C.E.L. might want to participate. I thought it is such a specific subject with such a potential impact for life extension that it deserves its own thread. I'm still surprised that it might be so simple. I'm awaiting your reactions
Edited by AgeVivo, 01 July 2009 - 09:52 PM.
AgeVivo 03 Jul 2009
i meant lobbying such that the new norm becomes that when such tests reveal good they are continued to also get lifespan statisticssimply don't stop toxicity/carcinogenesis tests so early
caliban 07 Jul 2009
Any scientist working in this field is unhappy about the sparse availability of aged and old rodent models. However, spaces in an animal house are limited and expensive. Who would pay for the extra upkeep and who would do the research that you suggest?
Top be clear, are you aiming to lobby policy makers to introduce a 'lifespan' testing requirement in preclinical studies?
brokenportal 07 Jul 2009
AgeVivo 07 Jul 2009
yes, completely.To be clear, are you aiming to lobby policy makers to introduce a 'lifespan' testing requirement in preclinical studies?
it would certainly help that changeAny scientist working in this field is unhappy about the sparse availability of aged and old rodent models.
The same ones who do the toxicology test. Everything is already is place (people, animal, treatments, materials, methods) so the extra cost and time is minimal and the data/cost ratio is optimal. Also animals are better used, rather than killed when they are 2 years old.However, spaces in an animal house are limited and expensive. Who would pay for the extra upkeep and who would do the research that you suggest?
AgeVivo 08 Jul 2009
Contacts: http://ntp.niehs.nih.gov/index.cfm?objecti...0032407A834B400
- Imagine: lifespan tests with 50 animals per group, at 3 doses, for both sexes, and mice and rats !!!
From http://ntp.niehs.nih...9A7F9CAA57DD7F5 :
The NTP long-term toxicology and carcinogenesis studies (bioassays) in rodents generally employ both sexes of rats (Fischer 344/N or Wistar Han) and mice (B6C3F1 hybrid) with three exposure concentrations plus untreated controls in groups of 50 animals for two years. - For many products!!!
Two-year studies in laboratory rodents remain the primary method by which chemicals or physical agents are identified as having the potential to be hazardous to humans.
- Methylene blue is an example of product for which 2 years was obviously TOO SHORT:
Where is the right-hand side of the graph?
Methylene Blue has since been recognized to extend [human] cell-lifespans, and is now being considered for MPrize @ home: http://www.imminst.o...showtopic=21310 ... - 274 such NTP studies are found on pubmed
By searching "National Toxicology Program"[Corporate Author]
You can access them one by one at http://ntp.niehs.nih...tml?col=010stat
Example: MB: http://ntp.niehs.nih...BE2C5310A792BB3
- All big pharmaceutical companies do such tests, afaik today their results are in general not easily accessible
- Many chemicals are also tested, for example with the REACH European regulations: http://ec.europa.eu/...reach_intro.htm
LIFESPAN MATTERS...
MANY products are ALMOST tested on lifespan...
* DON'T STOP TOXICITY TESTS SO EARLY! *
(...or start with 1 year old animals...)
Edited by AgeVivo, 08 July 2009 - 09:43 PM.
Mind 27 Aug 2009
AgeVivo 19 Sep 2009
a) machines for "virtual necropsies" are needed
they are in fact needed because many (most of the N=50) animals are needed to statistically detect effects on survival: continuing the toxicity tests with *a few* animals that do not have necropsy is not an alternative.Most animals are examined by necropsy after toxicity studies, so lifespan
studies are difficult. If "virtual necropsies" were performed, using
various imaging techniques, the cost/benefit ratio would be much better.
b) PET scans might do the trick
In studies looking for cancer, PET scans using 16F fluorodeoxyglucose could be used to detect cancer without hurting the animal. This is done all the time in humans and is also sometimes done in animals.
c) Contacts: tell them about the project if you meet them!
it doesn't seem like a bad idea, particularly when longevity studies
are becoming more common and so drug discovery groups may be willing to pay
a little more to see if there's an effect on longevity.
A preclinical CRO could pitch the study option to a potential client that
1/10th of the animals in a toxicity study will not be necropsied, but will
be kept for longevity studies (the client would decide the dosing regimen).
There still would be increased costs due to the animal husbandry,
additional compound, etc. The CRO could determine the price and make an
appropriate quote. Maybe you could find a funding source willing to
subsidize the added cost in exchange for making the results
publicly-available in a database.
Among the larger preclinical CROs you could mention the idea to are Charles
River Laboratories, SRI International, and Pacific Biolabs.
Don't hesitate to discuss about the project with people working there, don't hesitate to post their answer here! The more we are, the better
AgeVivo 10 Oct 2009
PET scans cost much, but it's really worth asking around how to extend toxicity tests into lifespan tests.