Can intermittent fasting change how we age?

February 9, 2021

Written by: Vanessa B. Sanchez

People are always looking for a new way to diet. Whether your intentions are to lose weight or find the foods that work best with your body, there are many kinds of diets, some of which become more or less popular over time. While most diets focus on what you eat, intermittent fasting (IF) is about when you eat. For example, some people practicing IF choose to eat only during a particular window of time during the day and do not eat outside of that window. Typically, intermittent fasters use the 16/8 rule, where one fasts for 16 hours a day and only eat during an 8-hour window. For example, a common eating window is between 7 am – 3 pm or 12 pm – 8 pm. IF appears to be safe and effective in helping people to lose weight or maintain a healthy lifestyle. Studies on humans have shown that IF has several positive effects on memory, heart, and tissue health and can prevent obesity¹. You may have heard that IF can even make you live longer. Where did this idea come from, and could it be true?

The concept of IF began in 1997 when two scientists, Drs. Richard Weindruch and Rajindar Sohal, put obese mice on a caloric restriction diet and found that they lived 50% longer in comparison to controls⁴. They were the first to suggest that fasting over a lifetime can slow aging and lengthen the lifespan of animals^1,4. However, it wasn’t until 2012 when several TV documentaries and books popularized people practicing IF by claiming it was an effective weight loss strategy³. IF involves regulating the timing rather than the caloric content of food intake, but scientists wondered if this type of fasting would also affect the lifespan.

Well, what can studies done in animals tell us about how IF might slow aging? A study by a team of scientists from San Diego State University examined the effects of intermittent fasting on aging using the fruit fly. To track the effects of fasting on aging, they observed the climbing behavior of middle-aged flies². Typically, flies live about 5 to 6 weeks. As they age, their climbing behavior and fine motor control begins to decline in an easily observed way when they are about 3 to 4 weeks old. By studying the effects of IF on this climbing behavior, researchers can get an idea whether IF is related to the rate of aging. They found that middle-aged flies that fasted displayed more youthful climbing behaviors and had longer lifespans in comparison to those that did not fast. 

As flies (and humans) age, the proteins that are the building blocks of the cell can clump together, forming aggregates. Neurodegenerative diseases like Alzheimer’s and Parkinson’s disease also involve protein aggregates in the brain. Researchers believe that the decline in climbing behavior as flies get older is likely due to the natural accumulation of protein aggregates in the brain?^2,5. To try to pinpoint why fasting flies seemed to age more slowly, they looked to see if the flies that had fasted displayed different amounts of neural aggregates. They found that aggregates were indeed reduced in flies that had fasted compared to older flies that did not fast². These findings suggest that IF might be slowing aging by preventing protein aggregates in the brain. Excited by these results, the researchers set out to understand exactly how fasting might be preventing these aggregates from building up. 

How exactly was this possible? The researchers took a closer look into the flies’ brains to find a link between fasting and aging. When looking at the neurons and glia (the brain’s support cells), they found that those flies who underwent mild IF displayed higher levels of a process called autophagy². Autophagy is a very important pathway in the cell that involves the clearing and recycling of cellular waste. Dysfunction in the autophagy pathway is believed to be one of the major causes of the kind of protein aggregation that leads to neurodegenerative diseases. Scientists found that middle-aged flies that do not undergo fasting normally have more neural aggregates because autophagy is acting much slower in these flies compared to earlier in life². As we age, autophagy slows down and can’t keep up with clearing out all the waste, so neural aggregates begin to accumulate! The scientists concluded that fasting could influence long-term maintenance of the nervous system by increasing our metabolism and slowing the decline of autophagy, thereby promoting longevity and potentially reducing the risk of developing neurodegenerative diseases^2,5. 

Next, the researchers wanted to dig even deeper into how IF was affecting aging. By using cutting-edge techniques to understand the fly’s inner workings, scientists can study the transcriptome of a fly. Nearly all cells that make up the fly contain the same DNA (also known as genes or genome) which is a blueprint for everything in the cell. DNA is transcribed to RNA (transcriptome), and then RNA is translated to protein (proteome). However, not every gene is transcribed in a cell and environmental influences like IF can determine which genes are turned “on” or “off.” The research team found that older flies that fasted displayed more youthful behaviors and many transcriptional similarities to young flies⁵. In short, IF impacts change at the transcriptional level, which correlates with the youthful behavioral changes observed in older flies. Most importantly, their findings reflected what they previously found: when flies fast, there is an increase in metabolism, proteolysis (protein breakdown) and autophagy (clearing of waste)⁵. Put simply, IF increases the breakdown of the cell’s building blocks and the cell’s ability to clear out the garbage. Collectively, their results support the notion that IF can improve youthful behaviors and longevity in aged flies. 

So, will IF make you live longer? What we know so far is that there are health benefits of IF, such as ameliorating obesity, insulin resistance, hypertension, and inflammation¹. Clinical trials in older folks have shown that IF can significantly improve verbal and working memory, executive function, and global cognition^6,7. Scientists are currently trying to learn more about how IF affects our lifespan by conducting more IF studies on humans. The studies done in animals provide hope that by studying the effects of IF in older people, we might find ways to mitigate and prevent the progression of neurodegenerative disease. 

Whether you choose to fast or not is entirely up to you! There are also more and less extreme versions of IF, such as fasting only two days a week or just skipping a midnight snack. The cool thing to keep in mind is that while you’re fasting, even if it’s just while you sleep, your body has more time to play catch up by cleansing itself!

References: 

1. de Cabo, R., & Mattson, M. P. (2019). Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine, 381(26), 2541-2551.
2. Ratliff, E. P., Kotzebue, R. W., Molina, B., Mauntz, R. E., Gonzalez, A., Barekat, A., … & Linton, P. J. (2016). Assessing basal and acute autophagic responses in the adult drosophila nervous system: the impact of gender, genetics and diet on endogenous pathway profiles. PloS one, 11(10), e0164239.
3. Tello, M. (2018). Intermittent Fasting: Surprising Update. Harvard Health Blog, Harvard Medical School, 26.
4. Weindruch, R., & Sohal, R. S. (1997). Caloric intake and aging. New England Journal of Medicine, 337(14), 986-994.
5. Zhang, S., Ratliff, E. P., Molina, B., El-Mecharrafie, N., Mastroianni, J., Kotzebue, R. W., … & Bray, W. A. (2018). Aging and intermittent fasting impact on transcriptional regulation and physiological responses of adult drosophila neuronal and muscle tissues. International journal of molecular sciences, 19(4), 1140.
6. Horie, N. C., Serrao, V. T., Simon, S. S., Gascon, M. R. P., dos Santos, A. X., Zambone, M. A., … & de Melo, M. E. (2016). Cognitive effects of intentional weight loss in elderly obese individuals with mild cognitive impairment. The Journal of Clinical Endocrinology & Metabolism, 101(3), 1104-1112.
7. Witte, A. V., Fobker, M., Gellner, R., Knecht, S., & Flöel, A. (2009). Caloric restriction improves memory in elderly humans. Proceedings of the National Academy of Sciences, 106(4), 1255-1260.

Cover Image by Morgan Housel from Unsplash.