A vaccine targeting aged cells mitigates metabolic disorders in obese
mice

Date:
June 30, 2020
Source:
Osaka University
Summary:
Researchers developed a novel vaccine that removes senescent T cells
from adipose tissues. They showed that vaccinated obese mice had
improved glucose tolerance and insulin resistance without showing
severe adverse events. These findings could help develop a novel
therapeutic tool.



FULL STORY ========================================================================== Aging is a multifaceted process that affects our bodies in many ways. In
a new study, researchers from Osaka University developed a novel vaccine
that removes aged immune cells and then demonstrated an improvement of diabetes-associated metabolic derangements by vaccinating obese mice.


========================================================================== Aged, or senescent, cells are known to harm their surrounding younger
cells by creating an inflammatory environment. A specific type of immune
cell, called T cell, can accumulate in fat tissues in obese individuals
in senescence, causing chronic inflammation, metabolic disorders and
heart disease. To reduce the negative effects of senescent cells on
the body, senotherapy was developed to target and eliminate these rogue
cells. However, as this approach does not discriminate between different
types of senescent cells, it has remained unknown whether specific
depletion of senescent T cells can improve their adverse effects on
organ physiology.

"The idea that eliminating senescent cells improves the organ dysfunction
that we experience during aging is fairly new," says corresponding author
of the study Hironori Nakagami. "Because senescent T cells can facilitate metabolic derangements similar to diabetes, we wanted to come up with a
new approach to reduce the number of senescent T cells to then reverse
the negative effects they have on glucose metabolism." To achieve their
goal, the researchers developed a novel vaccine targeting the surface
protein CD153 that is present on senescent T cells populating fat tissues, thereby ensuring that normal T cells are not affected. To test the effects
of their vaccine, the researchers fed mice with a high-fat diet to make
them obese and ultimately to mimic the metabolic changes seen in diabetes.

These include insulin resistance and an improperly functioning glucose metabolism, both of which can facilitate a deterioration of the eyes,
kidneys, nerves and the heart. When they vaccinated these mice against
CD153, the researchers observed a sharp decline of senescent T cells in
the fat tissues of the mice, demonstrating the success of their approach.

But did it improve glucose metabolism in the obese mice? To investigate
this, the researchers turned to a test that is widely used in clinically diagnosing diabetic patients and performed an oral glucose tolerance
test in the mice, in which blood glucose levels were measured for
up to 2 hours after giving the animals a known amount of glucose to
drink. Vaccination against CD153 was able to restore glucose tolerance
in obese mice. Unvaccinated obese mice, however, continued to have
difficulties metabolizing glucose after intake and took a much longer time
to reach similar blood levels as the vaccinated animals. The researchers
also measured the extent of insulin resistance, which is a cornerstone
of the metabolic changes seen in obesity and diabetes. Vaccinated mice
showed significant improvements in insulin resistance as compared with
the unvaccinated animals, demonstrating that the hormone that the body
produces to lower blood glucose levels functioned properly.

"These are striking results that show how reducing senescent T cells
in adipose tissues improves glucose metabolism of obese mice," says
Nakagami. "Our findings provide new insights into removing specific
senescent cells using specific vaccines and could potentially be used
as a novel therapeutic tool for controlling glucose metabolism in obese individuals."

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


========================================================================== Journal Reference:
1. Shota Yoshida, Hironori Nakagami, Hiroki Hayashi, Yuka Ikeda,
Jiao Sun,
Akiko Tenma, Hideki Tomioka, Tomohiro Kawano, Munehisa
Shimamura, Ryuichi Morishita, Hiromi Rakugi. The CD153 vaccine
is a senotherapeutic option for preventing the accumulation of
senescent T cells in mice. Nature Communications, 2020; 11 (1)
DOI: 10.1038/s41467-020-16347-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200630103601.htm

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