30 AUGUST 2007
Life is all about three things -- eating, sleeping and getting old. Think about it. You have to eat, you have to sleep, and you have no way to stop the biological clock from ticking. Anything else is unnecessary.
Of course, unless you're a cat, nothing but eating, sleeping and aging would make for a pretty unsatisfying life. If you have exciting extracurricular activities on your agenda, perhaps you'd like to spend less time sleeping, or more time eating, and certainly it would be nice to age a little (or a lot) slower. Even scientists think about these things, although real science hasn't yet caught up with the miracle cures for obesity and aging you hear on radio commercials.
Progress may soon be made, however, by exploiting the realization that aging,
sleeping and eating are not merely three separate indispensable aspects of
existence. In fact, a growing amount of evidence suggests, they are deeply
connected, with one influencing the other.
It all has to do with timing. Animals on Earth live by a clock that is intrinsic to the planet, a 24-hour cycle of light and darkness. In mammals, eyes transmit light into a small clump of brain cells called the SCN (for suprachiasmatic nucleus), part of the hypothalamus. Signals from the SCN orchestrate complex, genetically controlled chemical reactions that make you sleepy at night and wake you up in the morning, more or less on the schedule dictated by the Earth's rotation.
But this daily (circadian) clock does more than just manage your sleep schedule. It sets up rhythms throughout the body. Cells in your liver, heart, lungs and blood possess clocks of their own, which are coordinated by signals from the SCN. Body temperature and heart rate, for instance, depend on time of day. So sleep is just one of the body's daily cycles -- rhythms also regulate things like food processing in the liver and variations in hormone levels in the bloodstream.
It is well known that messing with the light cycle (flying across time zones, working night shifts) can screw up the SCN clock, causing jet lag and perhaps even raising the risk of hormone-related diseases. Various sleep disorders are certainly related to circadian rhythm problems, and some evidence even suggests that disrupting the clock accelerates cancer.
Less well known is that fiddling with food schedules can disrupt the circadian clock, too, sometimes with the effect of accelerating aging. On the other hand, reducing food intake slows aging down. So maybe food, sleep cycles and growing old are all part of a single complicated system, as Oren Froy and Ruth Miskin suggest in a recent paper in Progress in Neurobiology.
In recent years, experiments on rat and mice have shown that meal time can be more important than day-night signals for setting the body's clock. If rats can eat all they want, but only at a specific time, their body's activities, body temperature and hormone production settle into cycles set by the feeding time rather than by the SCN. When animals are allowed to eat much less than what they'd like to (in other words, calorie intake is restricted), body clocks are again affected, but in this case so is the master clock in the SCN.
And calorie restriction, other work has shown, extends the normal life span in various species, from worms to fruit flies. Studies in rats, mice and monkeys show the reduced calorie intake delays or prevents the onset of some diseases associated with aging, such as cancer and diabetes.
"Several theories explain how caloric restriction modulates aging and longevity, but the exact mechanisms are still unknown," write Froy, of the Hebrew University of Jerusalem, and Miskin, of the Weizmann Institute of Science in Rehovot, Israel.
Perhaps, Froy and Miskin suggest, the life-extending effect of fewer calories is related to the biological clock. After all, the circadian cycle generally grows shorter with age. If calorie restriction increases the length of the daily cycle, perhaps aging slows as well.
It's all perfectly plausible. Timing and amount of food can influence the activity of genes that play key roles in the chemistry underlying circadian rhythms. It would not be surprising if some of the circadian rhythm genes played roles in aging as well. One intriguing candidate is Sirt1, a gene implicated in the lengthening of life span by calorie restriction. Sirt1 produces an enzyme that can modify the activity of other genes, so it might affect genes involved in driving the circadian clock.
Many details in this story remain undiscovered, but prospects of slowing aging no longer seem entirely hopeless. Success would seem to depend, though, on understanding the complicated chemistry of food and sleep much more thoroughly.
"Resetting the biological clock by food or feeding time may lead to better functionality of physiological systems, preventing obesity, promoting well-being, and extending life span," Froy writes in another new paper, published in the current issue of Frontiers in Neuroendocrinology. "It is of extreme importance to understand the relationship between food, feeding, and the biological clock at the molecular level."
And that task will leave biologists with a lot to do as they grow older, while they're not sleeping or eating.
E-mail: tsiegfried@nasw.org
