Core Facility for Slow-Aging Mice

This Core is designed to produce mice in which lifespan is extended, and aging presumably slowed, by exposing the mice to drugs or nutritional supplements. The choice of drugs is based largely on the discoveries of the National Institute on Aging's Mouse Intervention Testing Program (ITP). In its initial work, the UM Glenn Center is producing mice treated with each of three drugs:

Rapamycin, which blocks the action of TOR kinase. Rapamycin has been shown to extend lifespan of both male and female mice, when started at 9 or at 20 months of age. At the highest doses of rapamycin tested so far, male mice live 23% longer, and female mice life 26% longer than ordinary control mice.

Acarbose, which slow down the conversion of starches to sugars and in this way blunts the rapid rise of blood sugar levels after a meal. Male mice treated with acarbose live 22% longer than control males. Acarbose also extends female lifespan, but by a smaller extent (5%).

17-α-estradiol, a chemical variant of the more familiar form of estrogen, 17-β-estradiol. Published studies show that 17-α-estradiol increases male lifespan by 12%, but does not affect lifespan of female mice.

In addition, the Core will produce two kinds of control mice, one in which the mice are exposed to normal food without any drug, and a "calorie restriction" control in which mice are given 60% of their normal food intake, a procedure that has been shown to extend healthy lifespan and postpone many of the harmful changes seen in old age.

Studies of slow-aging mice (Year 1):

Mice produced by the Core in the first year will be used by six collaborating researchers:

The laboratory of Henry Paulson will evaluate the effects of these drugs on brain biology, with particular attention to cellular systems that slow down neurodegenerative diseases by helping proteins fold properly.

The laboratory of Evan Keller will study the way in which these drugs postpone cancers, using a system that evaluates stages in the inception and growth of mouse bladder tumors.

The laboratory of Raymond Yung will test ideas about the contribution of inflammation, particularly in fat tissue, to the diseases of old age.

The laboratory of Karl Jepsen will look at the effects of slowed aging on bone and bone cell biology.

The laboratory of Charles Burant will evaluate the effects of these drugs on sugars, lipids, amino acids, and other small compounds present in the plasma of the treated mice.

The laboratory of Richard Miller will evaluate tissues from the mice for cellular traits thought to be involved in resistance to stress.

Information for potential collaborators:

The UM Glenn Center's Core Facility for Slow-Aging Mice plans to produce additional sets of mice, each year, to serve as the foundation for collaborations with other scientists, both at the University of Michigan and at other research institutions. Researchers who have projects that might involve a collaboration using mice treated with drugs that extend lifespan are invited to contact Dr. Miller at millerr@umich.edu.

Tissue archive:

The Core plans to establish an archive of frozen tissues from mice in each of the treatment groups. Mice will be started on the agents at 4 months of age (except for 17-α-estradiol, which is started at 10 months), and plasma and tissue samples obtained from mice at ages 12 or 22 months. The archive will contain, at a minimum, samples of liver, kidney, heart, skeletal muscle, visceral fat, and subcutaneous fat. Researchers who wish to obtain some of these samples for their own analyses are invited to contact Dr. Miller at millerr@umich.edu. Requests for tissues that are not already on the standard dissection protocol can also be considered.