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The ISS has had crew since the year 2000. Do the health issues with microgravity keep compounding, or do they stabilize after a few years and maybe even diminish? I suppose the animal needs to be a mammal, fairly big and long lived.

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    $\begingroup$ Technically, Polyakov is a mammal. $\endgroup$ – Deer Hunter Apr 21 '15 at 15:38
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    $\begingroup$ The longest time non-humans have spent in space is only 91 days. They were mice who lived in the mice drawer system on the ISS in 2012. See this NASA report on the results of the experiment. $\endgroup$ – kim holder Apr 22 '15 at 13:47
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437 days in a single stretch.

The mammal was a relatively standard specimen of Homo sapiens sapiens. Known affectionately as Valeri Polyakov by his handlers, the subject was launched to orbit on-board Soyuz TM-6 on August 29, 1988.

The mammalian subject was allowed free movement in a spacious 350 cubic meter enclosure, provided with a diet consisting of around 100 g of protein, 130 g of fat and 330 g of carbohydrates per day source, and allowed several trips outside during the course of his mission.
The subject was returned to Earth on-board Soyuz TM-7 on April 27, 1989.

The record for the longest total time any mammal has spent in microgravity is also held by a specimen of Homo sapiens sapiens; Sergei Krikalev, with 803 days in space.

As to the second part of your question:

Do the health issues with microgravity keep compounding, or do they stabilize after a few years and maybe even diminish?

We simply don't know. Even Polyakov's record holding flight didn't break the 18 month mark. The ongoing One Year Mission is a start towards the kind of long duration experiments that will eventually answer your question.

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