ALL ABOUT AGING
Aging Slowed, Longevity Increased by Controlling
Signals to Brain’s Hypothalamus
Einstein med school scientists may have found the
body's ‘fountain of aging’ - at least in lab mice
A new discovery that the brain region known as the
hypothalamus controls aging has enabled scientists to slow down the
aging process and increase longevity - at least in lab mice - by
altering signals to this area of the brain.
While the search continues for the Fountain of
Youth, these researchers at
Albert Einstein
College of Medicine of Yeshiva University, Bronx, N.Y., may
have found the body's "fountain of aging" in the hypothalamus.
For the first time, scientists report that the
hypothalamus of mice controls aging throughout the body. Their discovery
of a specific age-related signaling pathway opens up new strategies for
combating diseases of old age and extending lifespan. The paper was
published today in the online edition of Nature.
"Scientists have long wondered whether aging occurs
independently in the body's various tissues or if it could be actively
regulated by an organ in the body," said senior author
Dongsheng Cai,
M.D., Ph.D., professor of
molecular
pharmacology at Einstein.
"It's clear from our study that many aspects of
aging are controlled by the hypothalamus. What's exciting is that it's
possible — at least in mice — to alter signaling within the hypothalamus
to slow down the aging process and increase longevity."
The hypothalamus, an almond-sized structure located
deep within the brain, is known to have fundamental roles in growth,
development, reproduction, and metabolism. Dr. Cai suspected that the
hypothalamus might also play a key role in aging through the influence
it exerts throughout the body.
"As people age," he said, "you can detect
inflammatory changes in various tissues. Inflammation is also involved
in various age-related diseases, such as metabolic syndrome,
cardiovascular disease, neurological disease and many types of cancer."
About the Hypothalamus
The hypothalamus (from
Greek
ὑπό
= under and θάλαμος = room, chamber) is a
portion of the
brain that contains a number of small
nuclei with a variety of functions. One of the most
important functions of the hypothalamus is to link the
nervous system to the
endocrine system via the
pituitary gland (hypophysis).
The hypothalamus is
located below the
thalamus, just above the
brain stem. In the
terminology of
neuroanatomy, it forms the
ventral part of the
diencephalon. All
vertebrate brains contain a hypothalamus. In humans, it is
roughly the size of an
almond.
The hypothalamus is
responsible for certain
metabolic processes and
other activities of the
autonomic nervous system. It synthesizes and secretes
certain
neurohormones, often called
hypothalamic-releasing hormones, and these in turn stimulate
or inhibit the secretion of
pituitary
hormones. The hypothalamus
controls
body temperature,
hunger, important aspects of parenting and attachment
behaviors,
thirst, fatigue,
sleep, and
circadian cycles.
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Over the past several years, Dr. Cai and his
research colleagues showed that inflammatory changes in the hypothalamus
can give rise to various components of metabolic syndrome (a combination
of health problems that can lead to heart disease and diabetes).
To find out how the hypothalamus might affect
aging, Dr. Cai decided to study hypothalamic inflammation by focusing on
a protein complex called NF-κB (nuclear factor
kappa-light-chain-enhancer of activated B cells). "Inflammation involves
hundreds of molecules, and NF-κB sits right at the center of that
regulatory map," he said.
In the current study, Dr. Cai and his team
demonstrated that activating the NF-κB pathway in the hypothalamus of
mice significantly accelerated the development of aging, as shown by
various physiological, cognitive, and behavioral tests.
"The mice showed
a decrease in muscle strength and size, in skin thickness, and in their
ability to learn — all indicators of aging. Activating this pathway
promoted systemic aging that shortened the lifespan," he said.
Conversely, Dr. Cai and his group found that
blocking the NF-κB pathway in the hypothalamus of mouse brains slowed
aging and increased median longevity by about 20 percent, compared to
controls.
The researchers also found that activating the NF-κB
pathway in the hypothalamus caused declines in levels of gonadotropin-releasing
hormone (GnRH), which is synthesized in the hypothalamus. Release of
GnRH into the blood is usually associated with reproduction.
Suspecting that reduced release of GnRH from the
brain might contribute to whole-body aging, the researchers injected the
hormone into a hypothalamic ventricle (chamber) of aged mice and made
the striking observation that the hormone injections protected them from
the impaired neurogenesis (the creation of new neurons in the brain)
associated with aging.
When aged mice received daily GnRH injections for
a prolonged period, this therapy exerted benefits that included the
slowing of age-related cognitive decline, probably the result of
neurogenesis.
According to Dr. Cai, preventing the hypothalamus
from causing inflammation and increasing neurogenesis via GnRH therapy
are two potential strategies for increasing lifespan and treating
age-related diseases. This technology is available for licensing.
(Notes:
The title of the paper is "Hypothalamic Programming
of Systemic Aging Involving IKKβ, NF-κB and GnRH." The other
contributors are Guo Zhang, Ph.D.; Juxue Li, Ph.D.; Sudarshana
Purkayastha, Ph.D.; Yizhe Tang, Ph.D.; Hai Zhang, Ph.D.; Ye Yin, Ph.D.;
Bo Li, Ph.D. candidate; and Gang Liu, Ph.D.; all at Einstein.)
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