It's a cliché of vampire tales that young blood is preferable to old, but a new study suggests there's some truth to it.
A paper published today in Nature
finds that when younger mice are exposed to the blood of older mice,
their brain cells behave more like those found in aging brains, and vice
versa. The researchers who carried out the work also uncovered chemical
signals in aged blood that can dampen the growth of new brain cells,
suggesting that the decline in brain function with age could be caused
in part by blood-borne factors rather than an intrinsic failure of brain
cells.
Brain boost: Normally the brains of older mice (left) grow fewer
new neurons (dark brown) than when the animals were younger. But when
older mice shared the blood of younger mice, their neurons grew more
robustly (right).
To arrive at the discovery, the researchers studied pairs of old and
young mice that were literally joined at the hip. They used a technique
called parabiosis, in which two mice are surgically joined together
along the flank, which causes them to develop a shared circulatory
system. The technique has been used to study the development of the
blood system, and more recently has been used to investigate the effects
of age by joining old and young mice.
Lead author Tony Wyss-Coray,
a neuroscientist at Stanford University, says that five weeks after
creating these May-December pairings, "we found striking effects both on
the young and old brains." The young mice had a reduction in the
production of new neurons (neurogenesis), an increase in brain
inflammation, and less activity in synapses connecting neurons.
The older mice, in contrast, had an increase in new neurons, less
inflammation, and greater activity at synapses. "You could almost call
this a rejuvenation effect," Wyss-Coray says.
To see whether the effect could influence behavior, they injected, in
separate experiments, young mice with plasma from older mice and vice
versa, and found that old plasma impaired the younger animals' ability
to perform learning and memory tasks, whereas young plasma improved the
abilities of older mice.
Blood cells from one mouse cannot travel into the brain of the other
because of the blood-brain barrier, so the team concluded that
free-floating molecules in the blood, capable of passing through, must
be responsible for the effects. By comparing more than 60
chemokines—chemical messengers secreted by cells that circulate in the
blood—the researchers identified several associated with the detrimental
effect of old blood. Administering one of these chemicals, called
CCL11, to young mice dampened neurogenesis and impaired learning and
memory. CCL11 has been studied for its role in allergies and asthma, but
it's not clear how it influences neurons.
Richard Ransohoff,
director of the Neuroinflammation Research Center at the Cleveland
Clinic, who was not involved with the work, says that the work is
intriguing in the context of a study that last year linked neurogenesis
to the ratio of two different types of immune cells in the blood. Both
findings are "very, very surprising," he says, and suggest that "the
process of neurogenesis can be affected from outside the brain." Because
stem cells that give rise to new neurons "live in a microenvironment,
and that environment is very intimately associated with blood vessels,"
he says, these cells may be influenced by chemicals that travel through
the blood, including signals from the immune system.
Wyss-Coray says that the group will continue investigating whether
specific blood factors cause cognitive decline with age—or offer
protective effects in younger brains. Ransohoff also points out that
such factors could be useful as biomarkers for neurogenesis and other
signs of brain health, since the blood is vastly more accessible than
the brain.
By Courtney Humphries
From Technology Review
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