Protein in mitochondria appears to regulate health and longevity

Date:
June 24, 2020
Source:
University of Southern California
Summary:
A new study is the first to demonstrate that a tiny protein,
humanin, has a big impact on health and longevity in both animals
and humans.



FULL STORY ==========================================================================
A new study led by researchers at the USC Leonard Davis School of
Gerontology is the first to demonstrate that a tiny protein has a big
impact on health and longevity in both animals and humans.


==========================================================================
The researchers examined humanin, a peptide encoded in the small genome
of mitochondria -- the powerhouses of the cell. From experiments in
laboratory animals to measurements in human patients, the multi-site collaboration demonstrates how higher levels of humanin in the body are connected to longer lifespans and better health. It is linked to a lower
risk for diseases such as Alzheimer's.

"Humanin has long been known to help prevent many age-related diseases,
and this is the first time that it has been shown that it can also
increase lifespan," said senior author Pinchas Cohen, professor of
gerontology, medicine and biological sciences and dean of the USC Leonard
Davis School.

An intriguing evolutionary history Humanin has been found not only
in human mitochondria but also throughout the animal kingdom, a sign
that its related gene has been maintained, or conserved, throughout
evolution. The study, which was published online in the journal Aging
on June 23, examined humanin in several animal species, including worms
and mice, as well as humans, including Alzheimer's patients and children
of centenarians.

The results highlight the potential for humanin and other mitochondrial proteins to become treatments for age-related ailments. They also indicate
that humanin may be an ancient mitochondrial signaling mechanism that
is key for regulating the body's health and lifespan, said first author
and USC Leonard Davis Research Assistant Professor Kelvin Yen.



==========================================================================
More humanin, longer lifespans Humanin levels have previously been
observed to decrease with age in many species. In this new study, the scientists observed higher levels of humanin in organisms predisposed to
long lives, including the famously age-resistant naked mole rat, which experiences only a very slow decline in levels of humanin circulating
in the body throughout its 30-year lifespan.

In contrast, mice experience a 40% drop in humanin over the first 18
months of life, and primates such as rhesus macaques appeared to have
a similarly dramatic drop in humanin between the ages of 19 and 25.

In humans, researchers observed this phenomenon of higher and more
sustained levels of humanin in 18 children of centenarians, versus a
control group of 19 children of non-centenarians. Individuals whose
parents reach 100 years old are statistically more likely than other
people to reach very old age.

In some species, including worms and mice, modifying their genes to
produce higher amounts of humanin within their bodies was enough to significantly increase lifespans. But these longer-lived animals had
fewer offspring.

Scientists have observed a similar pattern in long-lived humans.



========================================================================== "This tradeoff between longevity and reproduction is thought to be due
to an evolutionarily conserved balance between using energy to produce
more offspring or using the energy to maintain the organism for future reproductive efforts," Yen said. "Evolutionarily speaking, the goal of
life is to reproduce and then you're done, but if you can't reproduce, you should try to hang around as long as possible, and a side effect of that
is longevity." Indication of -- and protection against -- disease Higher humanin levels aren't just linked to increased lifespan; lower levels
may increase the risk of disease and lower resistance to toxic exposures.

The researchers analyzed samples of cerebral spinal fluid from a small
number of Alzheimer's patients and control individuals without dementia
and noticed that humanin levels were much lower in the Alzheimer's
patients. And in newborn cord blood samples, high levels of humanin
correlated with a high mitochondrial DNA (mtDNA) copy number, or the
number of copies of the mitochondrial genome present within each cell.

"Humanin levels are inversely correlated with a decrease in mitochondrial
DNA (mtDNA) copy number, which in itself has been associated with a number
of different diseases such as cancer, kidney disease, and cardiovascular disease," Yen said.

Potential for treatments Cohen's laboratory was one of three groups that independently discovered humanin and has continued to unlock the secrets
of the mitochondrial genome.

Other promising mitochondrial peptides characterized by Cohen's
team include MOTS-c, which plays a role in communication between the mitochondria and the nucleus in cells and appears to mimic the effects
of exercise.

This new wide-ranging study highlights the importance of humanin as a potentially powerful regulator of lifespan and health, and harnessing
it for treatments could address a variety of age-related illnesses,
Cohen said.

"This study, as well as many others, suggest that humanin administration
would be an effective therapeutic treatment for a large number of diseases
and further solidifies the importance of the mitochondria beyond its traditional role as the 'powerhouse of the cell,'" he said.


========================================================================== Story Source: Materials provided by
University_of_Southern_California. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Kelvin Yen, Hemal H. Mehta, Su-Jeong Kim, YanHe Lue, James Hoang,
Noel
Guerrero, Jenna Port, Qiuli Bi, Gerardo Navarrete, Sebastian
Brandhorst, Kaitlyn Noel Lewis, Junxiang Wan, Ronald Swerdloff,
Julie A. Mattison, Rochelle Buffenstein, Carrie V. Breton,
Christina Wang, Valter Longo, Gil Atzmon, Douglas Wallace,
Nir Barzilai, Pinchas Cohen. The mitochondrial derived peptide
humanin is a regulator of lifespan and healthspan. Aging, 2020;
DOI: 10.18632/aging.103534 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200624151613.htm

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