Is autophagy a key to longevity?

© Dr. Michael D. Jacobson, D.O. Do not reproduce this article without permission.

From the June 2019 issue of Heartfelt Magazine.

In last month’s article I wrote about the world’s “Blue Zones,” where people live to be 100 years old at a rate 10 times greater than the U.S. population. What appears to be common among these Blue Zones, according to bluezones.com, are four basic components:

  1. Moving naturally (being active in your work and lifestyle)
  2. Having the right outlook (knowing your transcendent purpose and “down shifting” to a slower life pace)
  3. Eating wisely by limiting calories (following a plant-based diet and limiting calories; for example, Okinawan centenarians stop eating when they feel 80 percent full)
  4. Having a sense of belonging through relational connections and maintaining a closeness to family and cultural groups.

 

But what about the “rest of us” who don’t live in one of the Blue Zone cultural regions? Can we also attain this kind of longevity?

To answer this question, researchers reviewed data from the “Nurses’ Health Study,” in which nearly 79,000 nurses were followed from 1980 to 2014, and data from the “Health Professionals Follow-Up Study,” which involved over 44,000 subjects followed from 1986 until 2014. While analyzing over 34 years of data, researchers identified five low-risk lifestyle factors that coincide with longevity (notice how similar these are to the Blue Zone attributes):

  1. Following a healthy, plant-based diet
  2. Exercising at least 30 minutes daily
  3. Never smoking
  4. Limiting alcohol consumption to no more than one 5-ounce glass of wine per day
  5. Maintaining a body weight within the “ideal” range (a Body Mass Index, or BMI, between 18.5 and 24.9)

 

For subjects whose lifestyles were characterized by all five of these low-risk lifestyle factors at age 50, researchers found that men could expect to add an average of 12 years of life expectancy (i.e. from 76 years to 88) and women could expect an additional 14 years (extending from 79 to 93). The data concludes that, yes, people outside of a Blue Zone can significantly increase their longevity!

Yoshinori Ohsumi, a Japanese cell biologist, won the 2016 Nobel Prize in Medicine for his research on autophagy (a process in which cells recycle and renew themselves). Though autophagy—which literally means “self-eating”—was initially discovered in the 1960s, Ohsumi “created a whole new field of science with his work studying autophagy in [single-celled] yeast.” He identified that nearly identical autophagy genes were also present in higher organisms including humans and that mutations in these genes can cause disease. Ohsumi showed that autophagy plays a role in protecting organisms from famine, inflammation and diseases such as dementia and Parkinson’s.

Because autophagy appeared to be advantageous to good health, researchers began to ask, “Can autophagy be intentionally induced?” The answer, according to these scientists, is a resounding “Yes.”

Researchers have found at least two ways in which autophagy can be activated: exercise and fasting. Acute exercise appears to induce autophagy in the heart and skeletal muscles. In other words, getting out and exercising helps build muscle strength and helps muscle cells ‘clean’ themselves, renew and rejuvenate. Secondly, fasting for at least 12 to 24 hours also induces autophagy. Authors, however, seem to differ on this point: The speaker I originally heard stated that autophagy is only induced when fasting, or a fasting-like (mimicking) state, is present for over 30 hours.

But how does autophagy actually work?

Valter Longo, University of Southern California’s (USC) School of Gerontology Doctor of Philosophy and Director of USC’s Longevity Institute, noticed that centenarians have lower levels of a substance known as “Insulin-like Growth Factor-1” (IGF-1), which is also called “Somatomedin C”. This seemed to correlate with the discovery that humans who were born with Laron Syndrome, a mutation in the Growth Hormone Receptor (GHR), were protected from diseases such as cancer and diabetes. These diseases were common amongst those with normal growth hormone activity.

So just what is IGF-1? As its name implies, it’s a hormone similar to insulin that effectively communicates to the body’s cells the “orders” of growth hormone. Growth is not negative unless, like anything else, it becomes excessive. Not surprisingly, individuals with high levels of IGF-1 can suffer from enlarged organs and other diseases such as diabetes, cardiovascular disease, hypertension and arthritis. In other words, the top diseases that kill a majority of Americans are associated with high levels of IGF-1.

Sound significant? You bet.

Next month: Extending longevity with the Fasting-Mimicking Diet

References:

  1. Khan, Joel. “The Longevity Diet.” Lecture, Medical-Dental-Legal Update, South Lake Tahoe, February 1, 2019.
  2. 2018. “Fasting for Health and Longevity: Nobel Prize Winning Research on Cell Aging.” bluezones.com, Last Modified October, 2018, accessed April 3. bluezones.com/2018/10/fasting-for-health-and-longevity-nobel-prize-winning-research-on-cell-aging/
  3. He, C., M. C. Bassik, V. Moresi, K. Sun, Y. Wei, Z. Zou, Z. An, J. Loh, J. Fisher, Q. Sun, S. Korsmeyer, M. Packer, H. I. May, J. A. Hill, H. W. Virgin, C. Gilpin, G. Xiao, R. Bassel-Duby, P. E. Scherer, and B. Levine. 2012. “Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.” Nature 481 (7382):511-5. doi: 10.1038/nature10758.
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