Of course, this age related concept does not concern all types of

Of course, this age related concept does not concern all types of PH. We propose that selleck inhibitor our model consisting of studying survival of old animals under hypoxia accompanied or not by some treatment may be useful for studying the overall effects of PH treatments which are Inhibitors,Modulators,Libraries destined for aged per sons. If we accept the difference that time goes 30 to 40 times faster in mice, there is a surprisingly good match between our survival curves of old hypoxic mice, treated or not by DHEA, and the survival curves of COPD patients, mostly over 65 years old, treated or not by oxygenotherapy. This, may suggest that hypoxic mice survival could be a speeded up model for human PH sur vival. DHEA was detrimental to long term survival An appropriate control should not affect survival and should be transposable to humans.

However DHEA induced an unexpected decrease of survival after the age of 24 months Inhibitors,Modulators,Libraries compared to the control mice, and this may not at all apply to humans. In humans it was shown that DHEA may be safely administered to older persons at the daily oral dose of 50 mg for one year. In comparison, the doses used to treat PH in animals are larger. In fact, whereas in humans DHEA is a major steroid circulating in the blood, no detectable DHEA was found in the blood of laboratory animals such as mice or rats. Therefore, DHEA supplementa tion is pharmacological in mice and cannot be considered as a hormonal replacement therapy. The effect on lifespan of DHEA administration in mice has been studied several times. High doses of free DHEA incorporated into the diet have been shown to increase the lifespan of particular short lived mice.

As C57BL/ 6 mice do not seem to like DHEA, we prefered to use lower doses and the sulfate Inhibitors,Modulators,Libraries form in drinking water to avoid survival bias by caloric restriction, and we found that it reduced the lifespan of 21 month old male C57BL/6 mice. We are not the first to find that DHEAS does not extend the lifespan of mice. A previous study found that 10 times less DHEAS did not affect the lifespan of 12 month old male C57BL/6 mice. The authors suggested that the lack Inhibitors,Modulators,Libraries of effect could come from an insufficient dosage. Another study found that the intermediate dose of 0. 1 mg/ml in drinking water from weaning age insignificantly decreased the lifespan of genetically heterogeneous mice. We multiplied the dose by 3 and the decrease of lifespan became very signif icant.

Although multiple parameters make the compari sons complex, a global interpretation of these results would be that DHEAS Inhibitors,Modulators,Libraries in drinking water does not affect mouse lifespan at doses smaller than 0. 1 mg/ml and decreases mouse lifespan at larger doses. third In fact, positive effects of dehydroepiandrosterone may be present but masked by negative effects due to the dose and way of administration, such as long term hepatic distur bances.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>