Rapamycin Partially Reverses Accelerated Degeneration in OXYS Rats

OXYS rats are a laboratory breed engineered to show accelerated aging. They exhibit higher levels of oxidative free radicals than other rats, and degenerate more rapidly. Animal lineages are engineered this way to reduce the cost and duration of exploratory studies of aging or specific conditions of aging.

Here researchers show that rapamycin, demonstrated to extend life in mice in recent years, can partially reverse accelerated degeneration in OXYS rats. This is an expected result given the range of other work on rapamycin to date. It is, however, worth noting that enthusiasm for rapamycin is driven as much by the fact that it is already an FDA-approved drug as for its merits as a basis for treatments. The cost of obtaining new drug approval is very high and takes a long time, so that funding sources are steered towards favoring the development of marginal new uses for existing drugs rather than better forms of entirely new medicine:

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span in C elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months.

Here we show that rapamycin treatment decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wistar rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci.

Levels of Tau [were] increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. We conclude that rapamycin in low chronic doses can suppress brain aging.

Link: http://impactaging.com/papers/v5/n6/full/100573.html


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