healthy muscle tissue on the left is from a young mouse. The
ability of muscle to repair itself decreases with age, as
evidenced by the middle image of old muscle tissue, which shows
a lower density of muscle fibers, increased scar tissue and
inflammation. The addition of oxytocin to the blood of old mice
rapidly rejuvenates the old muscle, as shown on the right.
(Photos by Wendy Cousin and Christian Elabd, UC Berkeley)
June 13, 2014 – Researchers at UC Berkeley may not
have found the fountain of youth but they may be on to something that
can rejuvenate old muscle in senior citizens and it is already approved
for use in humans. Oxytocin - a hormone associated with maternal
nurturing, social attachments, childbirth and sex - is indispensable for
healthy muscle maintenance and repair, the study says, but it declines
with age in the mice used in the study.
The new study, was published June 10 in the journal
Nature Communications, presents oxytocin as the latest treatment
target for age-related muscle wasting, or sarcopenia.
A few other biochemical factors in blood have been
connected to aging and disease in recent years, but oxytocin is the
first anti-aging molecule identified that is approved by the Food and
Drug Administration for clinical use in humans, the researchers said.
Pitocin, a synthetic form of oxytocin, is already used to help with
labor and to control bleeding after childbirth. Clinical trials of an
oxytocin nasal spray are also underway to alleviate symptoms associated
with mental disorders such as autism, schizophrenia and dementia.
“Unfortunately, most of the molecules discovered so
far to boost tissue regeneration are also associated with cancer,
limiting their potential as treatments for humans,” said study principal
investigator Irina Conboy, associate professor of bioengineering.
“Our quest is to find a molecule that not only
rejuvenates old muscle and other tissue, but that can do so sustainably
long-term without increasing the risk of cancer.”
Conboy and her research team say that oxytocin,
secreted into the blood by the brain’s pituitary gland, is a good
candidate because it is a broad range hormone that reaches every organ,
and it is not known to be associated with tumors or to interfere with
the immune system.
A happy hormone
Oxytocin is sometimes referred to as the “trust
hormone” because of its association with romance and friendship. It is
released with a warm hug, a grasped hand or a loving gaze, and it
increases libido. The hormone kicks into high gear during and after
childbirth, helping new mothers bond with and breastfeed their new
“This is the hormone that makes your heart melt
when you see kittens, puppies and human babies,” said Conboy, who is
also a member of the Berkeley Stem Cell Center and of the California
Institute for Quantitative Biosciences (QB3). “There is an ongoing joke
among my research team that we’re all happy, friendly and trusting
because oxytocin permeates the lab.”
The researchers pointed out that while oxytocin is
found in both young boys and girls, it is not yet known when levels of
the hormone start to decline in humans, and what levels are necessary
for maintaining healthy tissues.
Christian Elabd and Wendy Cousin, both senior
scientists in Conboy’s lab, were co-lead authors on this study.
Previous research by Elabd found that administering
oxytocin helped prevent the development of osteoporosis in mice that had
their ovaries removed to mimic menopause.
Extra oxytocin more beneficial for the old
The new study determined that in mice, blood levels
of oxytocin declined with age. They also showed that there are fewer
receptors for oxytocin in muscle stem cells in old versus young mice.
To tease out oxytocin’s role in muscle repair, the
researchers injected the hormone under the skin of old mice for four
days, and then for five days more after the muscles were injured. After
the nine-day treatment, they found that the muscles of the mice that had
received oxytocin injections healed far better than those of a control
group of mice without oxytocin.
“The action of oxytocin was fast,” said Elabd. “The
repair of muscle in the old mice was at about 80 percent of what we saw
in the young mice.”
Interestingly, giving young mice an extra boost of
oxytocin did not seem to cause a significant change in muscle
“This is good because it demonstrates that extra
oxytocin boosts aged tissue stem cells without making muscle stem cells
divide uncontrollably,” Cousin added.
The researchers also found that blocking the
effects of oxytocin in young mice rapidly compromised their ability to
repair muscle, which resembled old tissue after an injury.
The researchers also studied mice whose gene for
oxytocin was disabled, and compared them with a group of control mice.
At a young age, there was no significant difference between the two
groups in muscle mass or repair efficiency after an injury. It wasn’t
until the mice with the disabled oxytocin gene reached adulthood that
signs of premature aging began to appear.
“When disabling other types of genes associated
with tissue repair, defects appear right away either during embryonic
development, or early in life,” said Conboy. “To our knowledge, the
oxytocin gene is the only one whose impact is seen later in life,
suggesting that its role is closely linked to the aging process.”
Future treatment options
Cousin noted that oxytocin could become a viable
alternative to hormone replacement therapy as a way to combat the
symptoms of both female and male aging, and for long-term health.
Hormone therapy did not show improvements in agility or muscle
regeneration ability, and it is no longer recommended for disease
prevention because research has found that the therapy’s benefits did
not outweigh its health risks.
In addition to healthy muscle, oxytocin is
predicted to improve bone health, and it might be important in combating
Conboy said her lab plans to examine oxytocin’s
role in extending a healthy life in animals, and in conserving its
beneficial anti-aging effects in humans.
She noted that there is a growing circle of
scientists who believe that aging is the underlying cause of a number of
chronic diseases, including Parkinson’s and Type 2 diabetes.
“If you target processes associated with aging, you
may be tackling those diseases at the same time,” said Conboy. “Aging is
a natural process, but I believe that we can meaningfully intervene with
age-imposed organ degeneration, thereby slowing down the rate at which
we become progressively unhealthy.”
Funding from the SENS Research Foundation, the
National Institute on Aging and the California Institute for
Regenerative Medicine helped support this research.