Quirks and Quarks

Young blood can rejuvenate old mice — and scientists are starting to understand why

Scientists have identified one possible mechanism for why transfusions of blood from young mice to older animals can rejuvenate muscle, brain and organ tissue.

Blood from young animals contains message packets with genetic information on how to make a longevity protein

Scientists have identified what they think is the secret ingredient in the blood of young mice that can reverse the effects of aging in older mice — a finding the researchers hope will extend to humans. (Aizar Raldes/AFP via Getty Images)

Several years ago, researchers discovered the rejuvenating effects that blood from young mice could have on muscles, brain, and liver function when circulated in older animals. Ever since, scientists have been trying to identify the secret ingredient in young blood that could be providing this beneficial effect. 

Researcher Fabrisia Ambrosio and her colleagues have now identified one possible candidate. They looked at small packages of material in the blood extracellular vesicles, or EVs. They found that in the blood of younger mice, these vesicles contain genetic instructions for a key protein associated with the rejuvenation of tissue.

Ambrosio is an associate professor at the University of Pittsburgh and the director of rehabilitation at the University of Pittsburgh Medical Center International.

Ambrosio said, in an interview with Bob McDonald on Quirks & Quarks, that EVs are produced by normal cells and contain a "cargo" that is communicated to other cells and tissues. 

We really want to pursue the ability of these extracellular vesicles [from the young blood] as a therapeutic approach, and so we're looking to see, can we engineer extracellular vesicles with this critical cargo?- Prof. Fabrisia Ambrosio, University of Pittsburgh

"Their cargo is a bunch of information in the form of nucleic acids and proteins and lipids [fats] that is really a reflection of the originating cell state," said Ambrosio. 

Like a message in a bottle, these EVs are ultimately taken up and interpreted by other cells. 

They gave old mice young blood with and without these special information packages, and found that the anti-aging effect they were looking for in the older mice's muscles disappeared when the EVs were removed. This suggested the EVs were carrying some important signal of rejuvenation.

File photo — The blood of young mice contain special packages with genetic instructions to make the longevity protein that when given to older mice, improves their muscle function. (Robert F. Bukaty/Associated Press)

Research paper in the journal Nature Aging

    Critical anti-aging cargo

    Using spectroscopy and machine learning, Ambrosio and her colleagues were able to look inside these EVs to see how they differed between the young and old mice.

    In the young blood's EVs, they found a large number of genetic instructions — or "transcripts" — to make a longevity protein, known as Klotho. 

    "The EVs, as we get older, seem to lose the number of Klotho transcripts. This is true in mice and it's also true in humans, though we don't really understand why exactly that is."

    Loss of muscle function and impaired muscle repair in old mice may be driven by aged extracellular vesicles (EVs), which carry fewer copies of these instructions than those in young animals. (Fabrisia Ambrosio/University of Pittsburgh/Nature Aging)

    Previous work had shown that this longevity protein, Klotho, helps to maintain mitochondria in cells. Mitochondria act as an energy source and are linked with the regeneration of muscle tissue by muscle stem cells, which produce new cells. 

    As Klotho levels decrease with age, stem cells lose their ability to form healthy new muscle cells at an injury site and create scar tissue instead. 

    "What we see is that there's scar tissue accumulation, and this is pretty much a characteristic of age tissue healing throughout our body, not just skeletal muscle." 

    Leveraging the therapeutic potential 

    Ambrosio is optimistic about how widely their findings may translate because Klotho is also important for organs and tissues throughout our body, including our brains. 

    "While we focused on skeletal muscle [in this study,] we know that age-related declines in Klotho levels are also associated with a decrease in cognition and brain health over time."

    Prof. Ambrosio is hoping to test her findings on a human geriatric population to see if the EVs containing Klotho similarly rejuvenate their muscle cells like it did with the mice. (Philippe Lopez/AFP via Getty Images)

    She hopes to one day test this in a geriatric population as an anti-aging therapeutic to see if it's possible to turn back the clock for older individuals to improve their muscles' ability to heal and improve age-related cognitive decline.

    "We really want to pursue the ability of these extracellular vesicles [from the young blood] as a therapeutic approach, and so we're looking to see, can we engineer extracellular vesicles with this critical cargo?"

      Produced and written by Sonya Buyting. Click on the link at the top of the page to hear the interview with Prof. Ambrosio.