Their results, which
appeared in Cell Metabolism, suggest that the substance, which is found
in many foods, could help keep our internal timekeepers up to speed.
Dr.
Gad Asher’s lab in the Department of Biological Chemistry investigates these
circadian clocks, trying to understand how these natural timekeepers help
regulate, and are affected by, everything from nutrition to metabolism.
In the
present study, he and his research student Ziv Zwighaft were following clues
that certain metabolites called polyamines could be tied to the functioning of
circadian clocks.
We get polyamines from food, but our cells manufacture them
as well. These substances are known to regulate a number of essential processes
in the cell, including growth and proliferation. And the levels of polyamines
have been found to naturally drop as we age.
Working
with mice and cultured cells, they found that, indeed, enzymes that are needed
to manufacture polyamines undergo cycles that are tied to both feeding and
circadian rhythms of day and night. In mice engineered to lack a functional
circadian clock, these fluctuations did not occur.
As
the researchers continued to investigate, they discovered a sort of feedback
loop: polyamine production is not only regulated by circadian clocks but, in
turn, also regulate the ticking of those clocks. In cell cultures, adding high
levels of polyamines more or less obliterated the circadian rhythm, while
maintaining low levels slowed the clock by around two hours.
“The polyamines
are actually an embedded part of the circadian clockwork,” says Dr. Asher.
The
scientists then asked how this plays out in younger and older mice, with their
naturally higher or lower polyamine levels. It is known that the circadian
clocks of elderly mice run more slowly; concomitantly, their polyamine levels
decline.
The team found they could slow down the clocks in the young mice by
administering a drug to inhibit polyamine synthesis. In contrast, adding a
polyamine to the drinking water of the older mice made their clocks run faster
than others of their age group and actually restored their function, similar to
that of the young mice.
Dr.
Asher and his team intend to continue investigating the function of polyamines
in circadian systems.
“This discovery demonstrates the tight intertwining
between circadian clocks and metabolism,” says Mr. Zwighaft. “Our findings
today rely on experiments with mice, but we think they might hold true in
humans. If so, they will have broad clinical implications,” Dr. Asher says.
“The ability to repair the clock simply, through nutritional intervention with
polyamine supplementation, is exciting and obviously of great clinical
potential.”
Dr.
Gad Asher’s research is supported by the Willner Family Leadership Institute;
the Yeda-Sela Center for Basic Research; the Adelis Foundation; the Abisch
Frenkel Foundation for the Promotion of Life Sciences; the Crown Endowment Fund
for Immunology Research; and the Samuel M. Soref and Helene K. Soref
Foundation.
The
Weizmann Institute of Science in Rehovot, Israel, is one of the world’s
top-ranking multidisciplinary research institutions. The Institute’s
3,800-strong scientific community engages in research addressing crucial
problems in medicine and health, energy, technology, agriculture, and the
environment.
Outstanding young scientists from around the world pursue advanced
degrees at the Weizmann Institute’s Feinberg Graduate School. The discoveries
and theories of Weizmann Institute scientists have had a major impact on the
wider scientific community, as well as on the quality of life of millions of
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