Cutting Calories May Extend Your Life

Cutting back on calories has several health benefits beyond trimming your waistline. New research in human subjects confirms the findings from past studies done on flies, worms, and mice: reducing calories could extend your lifespan.The latest study, done by researchers at Yale, points to a key protein that can be captured to increase human health through moderate calorie reduction. Years of research has indicated that calorie restriction in flies, worms, and mice can increase life span in lab conditions. Now people can join that data set.Appropriately titled “CALERIE” (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), the first clinical controlled trial of limiting calories was performed in over 200 healthy human subjects. The researchers initially recorded baseline calorie consumption. A subjects were then divided into two groups: one share of the subjects was asked to cut their calorie intake by 14% while the remaining subjects maintained their normal diets. The long-term health effects of calorie restriction were then evaluated over two years.According to Viswa Deep Dixit, Waldemar Von Zedtwitz Professor of Pathology, Immunobiology, and Comparative Medicine and author of the study, the goal of the study was to evaluate whether limiting calories had similar health benefits in humans as it did in lab animals. The team of researchers wanted to understand more fully what happens to the body when calories are restricted and how that restriction may lead to better health.As past research indicates that limiting calories can increase infections in mice, Dixit wanted to examine how calorie restriction might be associated with inflammation and the immune response. According to Dixit, who is also director of the Yale Center for Research on Aging, "Because we know that chronic low-grade inflammation in humans is a major trigger of many chronic diseases and, therefore, has a negative effect on life span [...] Here we're asking: What is calorie restriction doing to the immune and metabolic systems and, if it is indeed beneficial, how can we harness the endogenous pathways that mimic its effects in humans?"Dixit’s team began by examining the thymus gland, located above the heart. The thymus gland makes T cells, a type of white blood cell that’s a vital part of the immune system. The thymus ages at a more rapid pace than other organs. Once healthy adults reach the age of 40, 70% of the thymus gland is fatty and nonfunctional, according to Dixit. As the thymus ages, it creates fewer and fewer T cells. Elderly people are at higher risk for infections because as we age, the reduction of T cells leaves us with less ability to fight off new pathogens.Magnetic resonance imaging (MRI) was used for this study to evaluate whether functional differences existed between the thymus glands of subjects that restricted calories compared to those that did not. The thymi in calorie-restricted subjects had less fat and produced more T cells than they had at the beginning of the trial. There was no change in the functional volume of the thymi of the group that didn’t restrict calories."The fact that this organ can be rejuvenated is, in my view, stunning because there is very little evidence of that happening in humans," said Dixit. "That this is even possible is very exciting."Dixit and his team thought they’d also see effects on immune cells that the thymus produced, which might add to the overall benefits of limiting calories. Despite the change in the thymi, no change in gene expression was observed after two years of calorie restriction.Dixit and his team dug further and discovered that the action was in the microenvironment of the tissue and not the blood T cells. The body fat of participants was studied in the subjects at three time points: the start of the study, after one year, and after two years had passed.Changes in gene expression in fat tissue was observed after one year. Those changes were maintained through the second year. This suggests that some genes were involved in life extension in animals and that calorie-restricting targets could improve metabolic and anti-inflammatory responses in humans.The scientists further set out to observe if any changes in genes could be encouraging in terms of the health effects of calorie restriction. They focused in on PLA2G7, a group of platelet-activating factor enzymes that is inhibited with calorie restriction. PLA2G7 is a protein made by immune cells called macrophages.The alteration in PLA2G7 gene expression noted in subjects that limited calories suggested that the protein could be affiliated with the effects of calorie reduction. A trial in mice was conducted to see if PLA2G7 caused the effects seen with calorie restriction.According to Olga Spadaro, a former research scientist at the Yale School of Medicine and lead author of the mouse study, “reducing PLA3G7 in mice provided similar benefits to what was seen with calorie restriction in humans. Specifically, the thymus glands of these mice were functional for a longer time; the mice were protected from diet-induced weight gain, and they were protected from age-related inflammation.”PLA2G7 targets a certain action of inflammation known as NLRP3 inflammation. Reducing PLA2G7 protected older mice from inflammation. These results show that PLA2G7 helps drive the impact of calorie restriction. According to Dixit, "Identifying these drivers helps us understand how the metabolic system and the immune system talk to each other, which can point us to potential targets that can improve immune function, reduce inflammation, and potentially even enhance healthy lifespan."He believes PLA2G7 could be manipulated without calorie restriction and still obtain the benefits. "There's so much debate about what type of diet is better -- low carbohydrates or fat, increased protein, intermittent fasting, etc. -- and I think time will tell which of these are important," said Dixit. "But CALERIE is a very well-controlled study that shows a simple reduction in calories, and no specific diet, has a remarkable effect in terms of biology and shifting the immuno-metabolic state in a direction that's protective of human health."In the meantime, it can’t hurt to reduce calorie intake for clients with overweight or obesity that are under the age of 60. In a 2000 calorie diet, 14% of calories equates to 280 calorie reduction each day.So here are some simple calorie-saving tips!

• Kick the (regular) can of soda to the curb and save 140-200 calories per day.
• Knock off 150-200 daily calories by skipping the afternoon granola or protein bar.
• Cut the butter and sour cream from your baked potato and save 100-150 calories.
• Forgo the after-dinner bowl of ice cream and spare 250 or more calories!
• Skip the evening snack while you watch your favorite sitcom each night.
• Replace wine and beer with seltzer water to get rid of an extra 150-200 calories.

By Lisa Andrews, MEd, RD, LDJournal References:

1. O. Spadaro, Y. Youm, I. Shchukina, S. Ryu, S. Sidorov, A. Ravussin, K. Nguyen, E. Aladyeva, A. N. Predeus, S. R. Smith, E. Ravussin, C. Galban, M. N. Artyomov, V. D. Dixit. Caloric restriction in humans reveals immunometabolic regulators of health span. Science, 2022; 375 (6581): 671 DOI: 10.1126/science.abg7292
2. Timothy W. Rhoads, Rozalyn M. Anderson. Caloric restriction has a new player. Science, 2022; 375 (6581): 620 DOI: 10.1126/science.abn6576

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