Starving for Longer Life



Starvation hormone markedly extends mouse life span, researchers report

Drs. David Mangelsdorf, Yuan Zhang, and Steven Kliewer (l-r) have demonstrated that a
starvation hormone markedly extends life span in mice without the need for calorie restriction.

 

DALLAS – Oct. 16, 2012 – A study by UT Southwestern Medical Center researchers finds that a starvation hormone markedly extends life span in mice without the need for calorie restriction.

“Restricting food intake has been shown to extend lifespan in several different kinds of animals. In our study, we found transgenic mice that produced more of the hormone fibroblast growth factor-21 (FGF21) got the benefits of dieting without having to limit their food intake. Male mice that overproduced the hormone had about a 30 percent increase in average life span and female mice had about a 40 percent increase in average life span,” said senior author Dr. Steven Kliewer, professor of molecular biology and pharmacology.

The study published online in eLife – a new peer-reviewed, open access journal – defined average life span as the point at which half the members of a given test group remained alive. A study to determine differences in maximum life span is ongoing: While none of the untreated mice lived longer than about 3 years, some of the female mice that overproduced FGF21 were still alive at nearly 4 years, the researchers report.

FGF21 seems to provide its health benefits by increasing insulin sensitivity and blocking the growth hormone/insulin-like growth factor-1 signaling pathway. When too abundant, growth hormone can contribute to insulin resistance, cancer, and other diseases, the researchers said.

FGF21 is a hormone secreted by the liver during fasting that helps the body adapt to starvation. It is one of three growth factors that are considered atypical because they behave like hormones, which are substances created by one part of the body that have effects in other parts, the researchers said.
“Prolonged overproduction of the hormone FGF21 causes mice to live extraordinary long lives without requiring a decrease in food intake. It mimics the health benefits of dieting without having to diet,” said co-author Dr. David Mangelsdorf, chairman of pharmacology and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern.

“Aging and aging-related diseases represent an increasing burden on modern society. Drugs that slow the aging process would be very desirable. These findings raise the possibility of a hormone therapy to extend life span,” said Dr. Mangelsdorf, who runs a research laboratory with Dr. Kliewer. They first identified FGF21’s starvation-fighting effects in a 2007 study.

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Lead author Dr. Yuan Zhang, an instructor of pharmacology, said the study was considered risky because all involved understood it would be at least two years – an average mouse life span – before there would be any evidence of whether elevated production of FGF21 would affect longevity.

Previous research has found that FGF21 can reduce weight in obese mice. The mice that overproduced FGF21 in this latest study were lean throughout their lives and remained lean even while eating slightly more than the wild-type mice, the researchers said.

The hormone does have some downsides: FGF21 overproducers tended to be smaller than wild-type mice and the female mice were infertile. While FGF21 overproducers had significantly lower bone density than wild-type mice, the FGF21-abundant mice exhibited no ill effects from the reduced bone density and remained active into old age without any broken bones, the researchers said.

“FGF21 is not affecting their mobility. These guys are spry. They live nice, long lives,” Dr. Kliewer said. “But the decreased bone density and female infertility will require additional research to determine if it is possible to separate out the hormone’s life span-extending effects from its effect on bone,” he added.

The study was supported by the National Institutes of Health, the Robert A. Welch Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, and the HHMI.

UT Southwestern co-authors are Dr. Yang Xie, assistant professor of clinical sciences; Dr. Eric Berglund, postdoctoral researcher in the Division of Hypothalamic Research; Dr. Katie Colbert Coate, postdoctoral researcher in pharmacology; Dr. Tian Teng He, senior research associate in the Advanced Imaging Research Center; Dr. Takeshi Katafuchi, instructor of pharmacology; Dr. Guanghua Xiao, assistant professor of clinical sciences; Drs. Matthew Potthoff and Wei Wei, both postdoctoral researchers in pharmacology; and Dr. Yihong Wan, assistant professor of pharmacology. Drs. Ruth Yu and Ronald Evans of the Salk Institute in San Diego also participated in the research.

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http://www.utsouthwestern.edu/newsroom/news-releases/year-2012/october/starvation-hormone-mangelsdorf-kliewer.html

Can When You Eat Affect Your Health?

November 08 2012 |12,266views|

Story at-a-glance

• New research suggests that when you eat could be just as important as what you eat … and possibly even more so
• Mice that fasted for 16 hours a day stayed lean and healthy even when fed a high-calorie diet; their mouse counterparts that had access to food day and night became obese and showed blood sugar and liver problems despite eating the same number of calories
• Other research suggests fasting triggers a variety of health-promoting hormonal and metabolic changes similar to those that occur when you exercise, offering protection against chronic disease
• Fasting does not mean starving yourself; options for intermittent fasting include skipping breakfast, cutting off your food intake in the early evening or late afternoon, or even simply delaying meals, such as breakfast, until after you exercise

By Dr. Mercola

Intriguing new research is adding weight to the notion that when you eat could be just as important as what you eat... and possibly even more so.

You're probably aware that your body runs on a regular circadian rhythm that coincides with when you sleep and wake.

But each of your organs, including your liver, muscle, fat and gut, have their own clock, and certain organs work best at different times of the day.

Earlier studies support this premise, indicating that nighttime eating may contribute to weight gain; the latest study took this a step further and showed that nighttime fasting may be a powerful weight loss tool.

Is Fasting for 16 Hours Overnight the Key to Weight Loss?

Researchers from the Salk Institute fed mice a high-fat, high-calorie diet but altered when they were able to eat. One group had access to food both day and night, while the other group had access to food for only eight hours at night (the most active period for mice). In human terms, this would mean eating only for 8 hours during the day.

Despite consuming the same number of calories, mice that had access to food for only eight hours stayed lean and did not develop health problems like high blood sugar or chronic inflammation.¹ They even had improved endurance motor coordination on the exercise wheel. The all-day access group, on the other hand, became obese and were plagued with health problems including:

• High cholesterol
• High blood sugar
• Fatty liver disease
• Metabolic problems

This suggests that your body may benefit from the break it receives while fasting, whereas constant eating may lead to metabolic exhaustion and health consequences like weight gain. Researchers said their latest work shows it's possible to stave off metabolic disease by simply restricting when you eat with periodic fasting, or even by just keeping to regular meal schedules rather than "grazing" off and on all day.
They concluded:

"[Time-restricted feeding] is a nonpharmacological strategy against obesity and associated diseases."

Intermittent Fasting May be a Secret to Optimal Health and Weight Loss

Because of the research above, combined with many other compelling pieces of evidence, some mentioned below, I have revised my personal eating schedule to eliminate breakfast and restrict the time I eat food to about seven to eight hours, which is typically from noon to 6 or 7 p.m. Just seems to make sense that our ancestors rarely had access to food 24/7 like we do and our genes are optimized for intermittent fasting.
It takes about six to eight hours for your body to metabolize your glycogen stores and after that you actually start to shift to burning fat. However, if you are replenishing your glycogen by eating every eight hours, you make it far more difficult for your body to use your fat stores as fuel.

It's long been known that restricting calories in certain animals can increase their lifespan by as much as 50 percent, but more recent research suggests that sudden and intermittent calorie restriction appears to provide the same health benefits as constant calorie restriction, which may be helpful for those who cannot successfully reduce their everyday calorie intake (or aren't willing to).

Fasting has been used as a spiritual practice in many cultures since ancient times, but it might have been done for health purposes as well. Modern science has confirmed there are many health reasons for fasting, including:

• Normalizing your insulin sensitivity, which is key for optimal health as insulin resistance (which is what you get when your insulin sensitivity plummets) is a primary contributing factor to nearly all chronic disease, from diabetes to heart disease and even cancer
• Normalizing ghrelin levels, also known as "the hunger hormone"
• Promoting human growth hormone (HGH) production, which plays an important part in health, fitness and slowing the aging process
• Lowering triglyceride levels
• Reducing inflammation and lessening free radical damage

A recent animal study published in the International Journal of Endocrinology showed a beneficial glycemic effect that resulted in a lower gain in body weight than in non-fasting animals.² Other research suggests fasting triggers a variety of health-promoting hormonal and metabolic changes similar to those that occur when you exercise, which may help prevent age-related brain shrinkage and other chronic and debilitating diseases such as Alzheimer's and Parkinson's. As for weight loss, here are three studies from recent years investigating fasting for weight loss, all of which showed positive results:

• Non-obese patients lost an average of four percent of their total fat with alternate-day fasting for 22 days. Their fasting insulin also decreased.³
• Alternate-day fasting was also effective for obese patients in a 2009 study. On fasting days, participants consumed 25 percent of their daily calorie needs. On average, they lost just over 5.5 pounds in eight weeks, and about three percent of their total body fat. Total cholesterol and LDL ("bad") cholesterol decreased, while HDL ("good") cholesterol remained unchanged. Systolic blood pressure also decreased.⁴
• In young, overweight women, alternate-day fasting was just as effective as calorie restriction for promoting weight loss and improving metabolic markers.⁵

Exercising While Fasting May Be Most Beneficial of All

Recent research suggests fasting before exercise may help you to achieve your fitness results faster by forcing your body to shed fat. This happens because your body's fat burning processes are controlled by your sympathetic nervous system (SNS), and your SNS is activated by both exercise and lack of food. The combination of fasting and exercising maximizes the impact of cellular factors and catalysts (cyclic AMP and AMP Kinases), which force the breakdown of fat and glycogen for energy.

According to some fitness experts, such as Ori Hofmekler, fasting may indeed push your exercise program to the next level. The reason for this is because exercise and fasting yield acute oxidative stress, which is actually essential for maintaining optimal muscle.

Many find it works out well to skip breakfast like I do, exercise, and then break their fast after working out, which would allow you to get the best of both worlds: the benefits of working out in a fasted state, and protein-loading for recovery about half-an-hour to an hour afterward. On the days that I exercise in the morning, I will have two scoops of Pure Power Protein about 30 minutes after the workout to provide nutrients, especially leucine, for muscle growth and repair.

Interestingly, since adopting this approach for the past few months I have lost two inches from my waist size and gained three pounds, which means I have lost body fat and gained muscle mass. This has been a personal experiment of mine to see if I can get back to my high school waist size of 32 inches, even though I weighed 20 pounds less back then.

Fasting is Not Starving Yourself

Fasting does not mean abstaining from ALL food for extended periods of time; this can be dangerous and counterproductive. Rather, intermittent fasting is a dramatic reduction of calorie intake at regular intervals – whether you opt for a 16-, 20-, or 24-hour fast once or twice a week, or fasting every other day, or simply delaying certain meals, such as skipping breakfast and exercising on an empty stomach.

There are many options, and you can discover what works best for you by listening to your body, and going slow; work your way up to full-day fasts if your normal schedule has included multiple meals a day. Or try ending your meals earlier in the evening or late afternoon and fast overnight while you sleep.

If you're hypoglycemic, diabetic, or pregnant (and/or breastfeeding), you need to be extra cautious with fasting, and may be best served to avoid it entirely, until you've normalized your blood glucose and insulin levels, or weaned your baby. But if you're healthy, intermittent fasting is likely to give your health a boost, especially if you've already mastered a nutritious diet, which really should be your first step.

When you cut out or delay meals for fasting purposes, it becomes all the more important to maximize the nutrients when you do eat. Fasting combined with a highly processed, toxin-rich diet is not going to do your health any favors. Instead, review my nutrition plan for ideas of what constitutes a healthy diet, so you'll be armed with the nutrition you need to thrive during your non-fasting hours.

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