On this day in medical history: Yoda, the oldest living lab mouse, died

Yoda the mouse died on April 22, 2004. At the time, he was the oldest living laboratory mouse, surviving 4 years and 12 days. That’s about double the lifespan of the average mouse, or the equivalent of about 136 human years, said Yoda’s keeper, Richard Miller, MD, PhD, professor of pathology, Geriatrics Center, University of Michigan Medical School, Ann Arbor, MI.

Yoda, a dwarf mouse, was less than half the size of a typical mouse. He was born with a gene mutation that disabled production of normal amounts of growth hormone. “The upside to my hormone deficiency is extreme life extension,” Yoda told Popular Science shortly before his death. “Together we [he and Dr. Miller] have shown conclusively—in mice—that too much growth hormone early on in life speeds up aging and too little can slow it down.”

Because he aged slowly, Yoda had both a long and a healthy life. Diseases of aging—such as arthritis, cataracts, and cancers—are delayed in dwarf mice like Yoda.

The Force was with him

But dwarfism had disadvantages, too. Due to their hormone deficiency, dwarf mice have difficulty maintaining body temperature. They’ll freeze to death if left alone. So, Yoda always had a full-sized mouse companion to snuggle with and keep warm. His last cuddle companion was named Princess Leia, but he outlived three of her predecessors.

“These losses have been tough, but I do take comfort in the fact that I’m helping science unravel the mysterious connection between growth hormone and aging,” Yoda explained. “It’s still astounding to me to think that a single genetic mishap can inadvertently extend the lifespan in mice by an average of 40%, and in my case, much more. Imagine what it could do for humans.”

Dr. Miller has imagined it. “We would like to be able to translate the mouse findings to figure out ways to produce medicines basically, so that people in their 80s, 90s, up to the age of 100, 110 perhaps, are also active and viable and have good cognitive powers and retain most of the kinds of functions they had when they were middle-aged,” he explained on Australia’s The Science Show.

Why study aging in mice? Because mice and humans are genetically similar, sharing about 95% of the same protein-coding genes. But the mouse’s much shorter lifespan makes longevity studies practical.

Thank you for being a friend

Although Yoda was the oldest living mouse in his day, some other laboratory mice have survived longer. One of the “Golden Girls” at Jackson Laboratory, Bar Harbor, ME, lived 4 years and 9 months. This mouse was of the Diversity Outbred strain, which are bred to be exceptionally genetically diverse.

In June 2003, the Methuselah Foundation awarded its first Methuselah Mouse Prize for the longest living lab mouse. The idea for the contest was to draw public attention and lend credibility to longevity research, which has been openly frowned upon. The prize went to Andrzej Bartke, PhD, for his mouse GHR-KO 11C, which lived for 1,819 days at Southern Illinois University (SIU), Springfield, IL. The mouse died just a week short of its fifth birthday.

Dr. Bartke, director of Geriatric Medicine at SIU School of Medicine, altered a gene controlling the mouse’s response to growth hormone, which reduced levels of insulin and glucose in its blood. The change apparently protected its DNA from age-related decay, keeping GHR-KO 11C alive for the equivalent of 180 to 200 human years.

Not to be outdone, the oldest known pet mouse was a house mouse named Fritzy, of Edgbaston, UK, who lived 7 years and 7 months, according to Guinness World Records. Fritzy died on April 24, 1985, almost 19 years to the day before Yoda went to the great cheese cupboard in the sky.