NIH Record - National Institutes of Health

Wagers Tracks Aging in Muscle Cells

Dr. Wagers
Dr. Amy Wagers

Photo:  Bill Branson

You don’t need to be a gym rat to know that muscle matters; without it, we wither toward our own personal finish line.

“Declining muscle function is a significant contributor to deficiencies in health and a powerful predictor of mortality,” said Dr. Amy Wagers, who studies how tissues maintain themselves and how they regenerate over time.

Wagers is Forst family professor of stem cell and regenerative biology at Harvard University and Harvard Medical School, senior investigator, Joslin Diabetes Center and principal faculty, Harvard Stem Cell Institute. In a talk titled “Stem cells, aging and aging stem cells” on Apr. 5 in Masur Auditorium, she reviewed how aging impairs stem cell function.

Those who maintain it is hell getting old already know the practical implications of the loss of unipotent satellite cells, which regrow muscle after damage.

Like man, mice lose satellite cells as they get older. An old mouse has about half of its original store of such cells, said Wagers, and those that remain are less robust than they were in the springtime of life, no longer responding as vigorously to damage signals. In their number, function and genomic profile, satellite cells figuratively hurtle toward Earth with age.

Hodes speaks with Wagers
NIA director Dr. Richard Hodes chats with Wagers after her Mahoney Lecture.

Photo:  Bill Branson

Examining the transcriptional profile of satellite cells in mice, Wagers and her colleagues have discovered “arrested myogenic differentiation due in part to accumulated DNA damage.”

Nearly all animal cell types make use of a substance called NF-KB (nuclear factor kappa light chain enhancer of activated B cells), which is thought to be a master regulator of inflammatory responses in mammals. Wagers and her team have shown that NF-KB regulates the aging of satellite cells and have proven its involvement in muscle degeneration.

Her studies have shown that blunting NF-KB activity delays the emergence of age-related defects in muscle cells. Further, she has shown that lipid mediator production plays a role in NF-KB function, driven in part by a gene called PLA2G5.

One other protector from the ravages of aging is caloric restriction.

Wagers and her colleagues have shown that the factors “impact multiple age-related phenotypes in diverse tissues.”In somewhat deeper dives into the chemical pathways of aging, Wagers and colleagues have conjoined young and old mice to examine how blood-borne factors from younger partners may improve function within the older animal—this is called “heterochronic parabiosis.”

One protein has stood out as a factor in the aging process—GDF11, whose expression varies with age and which may be regulated by immune cells.

Wagers stands with her hands folded
“There are many avenues to promote regenerative function,” Wagers said.

Photo:  Bill Branson

In mice, GDF11 supplementation has been shown to reverse cardiac hypertrophy, said Wagers. GDF11 appears to have a tantalizing “anti-geronic” action.

“But it depends on the dose and the context,” cautioned Wagers. “It can have negative [pro-geronic] effects too…[GDF11] has an interesting relationship with aging and might be a target for therapy someday.

“There are many avenues to promote regenerative function,” Wagers concluded. 

Meanwhile, it’s probably still best to take your muscles regularly to the gym.

Wagers’ talk, which can be seen in full at https://videocast.nih.gov/summary.asp?Live=22115&bhcp=1, was the annual Florence S. Mahoney Lecture on Aging, named in honor of Florence Stephenson Mahoney (1899–2002). She devoted the last half of her life to successfully advocating for the creation of the National Institute on Aging and increased support for NIH.—Rich McManus  

The NIH Record

The NIH Record, founded in 1949, is the biweekly newsletter for employees of the National Institutes of Health.

Published 25 times each year, it comes out on payday Fridays.

Assistant Editor: Eric Bock
Eric.Bock@nih.gov (link sends e-mail)

Staff Writer: Amber Snyder
Amber.Snyder@nih.gov (link sends e-mail)