Aches, Age & Influenza:

What We Know About Flu-Induced Muscle Loss and How to Prevent It

By Kim Krieger

the Flu

Why does age impact flu-related muscle loss, and how can we prevent it? UConn Health researchers are on the case.

Muscle mystery

Most of us have seen it happen to a relative, friend, or patient. A formerly healthy senior gets a bad case of the flu. When they recover, they’re weak from muscle loss, sometimes permanently disabled. We don’t know exactly why the muscle loss happens, but UConn researchers are finding ways to prevent it.

It used to be that losing muscle was just a part of getting old. It’s considered normal aging. You can’t get a drug approved by the FDA to treat aging, because aging isn’t considered a disease. But influenza, the virus that causes the flu, is. If getting the flu speeds up muscle loss in seniors, then muscle loss is potentially preventable. But how could a virus that only infects the lungs cause muscle loss?

Wasting away

When immunologist Laura Haynes first came to UConn Health, she knew that when mice get the flu, they lose weight. In fact, that’s the way researchers can tell that a mouse has the virus. Some mice lose more, some less. Haynes’ work had previously shown that older mice with the flu not only get much sicker, but also lose more weight than younger mice. But as an immunologist, her research focused on how aging immune systems decline. Differences in weight loss were an afterthought. But when she sat down with Dr. George Kuchel, director of the UConn Center on Aging, they made the connection that weight loss might indicate future disability.

Haynes teamed up with kinesiologist Jenna Bartley to further investigate. They confirmed that a significant amount of the weight lost by mice infected with the flu was muscle. And older mice infected with influenza lost more muscle than younger mice, and continued to lose it over a longer period of time.

It’s really hard to improve elderly immune response. So if we can’t prevent them from getting the flu, maybe we could at least prevent muscle loss and future disability.

“In mice there are changes in gene expression in muscle during influenza infection. Genes that degrade muscle go up, genes that build muscle go down. But in young mice, the gene expression goes back to normal more quickly,” says Haynes. The older mice, on the other hand, had higher levels of inflammation, muscle wasting, and atrophy, and it all persisted longer.

Exacerbated muscle loss wasn’t the only problem experienced by the older mice recovering from the flu. They also moved less and took fewer, narrower steps. It was as if they had become frailer and more easily tired. Decreasing gait speed, or how fast someone walks, indicates increasing frailty in humans, and taking narrower steps also increases the risk of falling. [See ‘UConn Pilots Quick Gait-Speed Measurement’]

Haynes and Bartley’s research was the first that directly linked flu-induced inflammation in a controlled setting to muscle atrophy and functional impairment. It was published in the April 2016 issue of the journal Aging. But now that they knew flu really was causing muscle wasting, how could they stop it? Even yearly vaccination doesn’t provide 100-percent protection.

“It’s really hard to improve elderly immune response. So if we can’t prevent them from getting the flu, maybe we could at least prevent muscle loss and future disability,” says Bartley.

Stemming the tide

Haynes and Bartley suspected that influenza-induced inflammation was related to, and possibly the cause of, the destruction of muscle tissue in the elderly mice. They theorized that if they could stem the tide of inflammation in the body, they might prevent the muscle tissue from degrading so much. But there was a catch: inflammation helps mobilize the immune system. If you block inflammation totally, you block the body’s defense against the flu virus. So Haynes and Bartley needed a more subtle tool.

In mice there are changes in gene expression in muscle during influenza infection. Genes that degrade muscle go up, genes that build muscle go down. But in young mice, the gene expression goes back to normal more quickly.

The first drugs Bartley and Haynes found that might be good candidates are COX-2 inhibitors. They’re non-steroidal anti-inflammatories, like aspirin and ibuprofen, but COX-2 inhibitors are very specific. They block just one molecule in the body’s web of inflammatory responses. Other researchers have shown that COX-2 inhibitors can slow muscle wasting in cancer patients. And most importantly, COX-2 inhibitors don’t seem to block the body’s antiviral immune reaction.

Haynes and Bartley are currently testing the COX-2 inhibitors to see if they prevent muscle loss in geriatric mice after the flu. They’re also testing whether improving immune memory of the flu in mice — that is, vaccinating them — protects them against muscle wasting.

Their work is intriguing, but Kuchel cautions that adult humans are more complicated than lab mice.

“Factors that may contribute to an older individual becoming more vulnerable to losing muscle function during or after flu infection are complex but may include a sedentary lifestyle, slow walking speed at baseline, low muscle mass, poor nutrition, plus chronic inflammation as a result of any number of chronic infections, being frail, etc.,” he says.

Bartley and Haynes agree. They’re applying for more grant money to explore how COX-2 inhibitors interact with other factors such as exercise. And they hope to eventually test muscle-protection strategies in people. Because while influenza is one of the most common serious infections in the elderly, it probably isn’t alone in causing muscle wasting.

“We’re trying to establish the relationship between any infection and inflammation, and how it leads to muscle loss and disability,” says Bartley. “Overall, we’re trying to help people get better and stay stronger for longer.”

When Getting Your Flu Shot, Timing is Everything

Elderly patient being tended to by a nurse

Pharmacies advertising flu vaccinations in August and September are doing their elderly clients a disservice, say UConn Center on Aging researchers. The immunity they gain from vaccine in late summer may wane by the time flu season hits hard in late winter.

As summer temperatures peaked this August, pharmacies were already advertising the influenza vaccine. But if you thought that was too early to be getting a flu shot — you were right.

If you’re interested in volunteering for the study, contact Lisa Kenyon at the UConn Center on Aging at 860.679.3956.

“When adults get the vaccine in September, the peak effect wears off by late December. But flu season peaks in January and February,” warns Laura Haynes, an immunologist and gerontologist at UConn Health.

October or November is a much better time to get the vaccine. That way, you’re still protected when virus season is at its worst.

This is especially important for the elderly, who are at particular risk from flu. People over 65 are much more likely than younger adults to have serious complications or even die from a bout with the virus.

One way to better stimulate the immune response is to administer a high-dose vaccine, which contains four times as much flu antigen as the regular version. But the high-dose vaccine has stronger side effects, is more expensive, and may not be best for everyone.

Haynes and her colleagues at UConn Health, funded by a Program Project Grant from the National Institute on Aging, will run two studies this autumn to better understand older people’s responses to the regular flu vaccine and the high-dose version. The studies will look at how the immune system reacts to the flu vaccine, as well as how to identify patients who would benefit from the high-dose version.