Anti-Aging: Study Shows How Complexity in Diet Affects Aging

A new study led by experts in Penn State’s College of Health and Human Development examined how caloric restriction affects humans’ telomeres — the regions of genetic bases that serve as protective caps at the ends of chromosomes.

The researchers’ findings were published in the journal Senescent Cells. Researchers analyzed data from a two-year caloric restriction trial in humans and found that humans who reduced calories lost telomeres at a different rate than those in the control group, even though both groups had nearly identical telomere lengths at the end of the study. Studies have found that 20% to 60% caloric restriction can promote lifespan extension in many species.

Over the course of human life, every time a person’s cells replicate, some of the telomeres are lost as the chromosomes are copied to the new cells. When this happens, the overall length of the cell’s telomeres becomes shorter. After cells replicate enough times, the protective caps on telomeres disappear completely. The genetic information in the chromosomes may then become damaged, preventing the cell from reproducing or functioning properly in the future. Cells with longer telomeres are functionally younger than cells with short telomeres, meaning two people with the same chronological age may have different biological ages depending on their telomere length.

Idan Shalev, associate professor of biobehavioral health at Penn State University, said that typical aging, stress, disease, genetics, diet, etc. all affect the frequency of cell replication and the length of telomere retention. Shalev led researchers who analyzed genetic samples from the national CALERIE study, the first randomized clinical trial of caloric restriction in humans. Shalev and his team sought to understand the effects of caloric restriction on telomere length in humans. Since telomere length reflects how quickly or slowly a person’s cells age, examining telomere length could allow scientists to find a way that caloric restriction could slow aging in humans.

“There are many reasons why caloric restriction may extend human lifespan, and the topic is still under research,” said Waylon Hastings, who earned his PhD in biobehavioral health from Penn State in 2020. is also the lead author of the study. “A major mechanism for extending lifespan has to do with metabolism within cells. When energy is consumed within cells, the waste products produced by this process can cause oxidative stress, which damages DNA and otherwise breaks down cells. When a person’s cells consume less However, due to caloric restriction, there is less waste and cells do not break down as quickly.

Researchers tested telomere length in 175 study participants using data from the beginning of the CALERIE study, one year into the study, and 24 months after the end of the study after calorie restriction. About two-thirds of the study participants participated in caloric restriction, while one-third served as a control group.

Over the course of the study, results showed that telomere deletions altered trajectories. Over the first year, participants who restricted their caloric intake lost weight, and they lost telomeres faster than the control group. After a year, the weight of the calorie-restricted participants stabilized, and the calorie restriction was continued for another year. In the second year of the study, participants who restricted calories lost telomeres at a slower rate than those in the control group. At the end of two years, the two groups had converged, and there was no statistical difference in telomere length between the two groups.

“This study shows the complexity of how caloric restriction affects telomere loss,” Shalev said. “We hypothesized that calorie-restricted humans would lose telomeres more slowly. Instead, we found that calorie-restricted humans initially lost telomeres more quickly and then lost them more slowly after their weight stabilized.”

The results raise a number of important questions, Shalev said. For example, what would happen to telomere length if data were collected for another year? Study participants plan to collect data over a 10-year follow-up, and Shalev said he is eager to analyze the data when it becomes available.

Although the results are not clear-cut, Shalev said caloric restriction is expected to provide potential health benefits in humans. Previous research on CALERIE data suggests that caloric restriction may help reduce bad cholesterol and lower blood pressure. Shalev and Hastings say that for telomeres, two years is not enough time to show benefits, but they may still be revealed.

Three of Shalev’s trainees, Hastings, current graduate student Qiaofeng Ye, and former postdoctoral scholar Sarah Wolff, led the research under Shalev’s guidance.

Hastings said the opportunity to lead this research was critical to his career.

“I was recently hired as an assistant professor in the Department of Nutrition at Texas A&M University, a position I will begin in the fall semester,” Hastings said. Before this program, I had limited experience with nutrition. This program has truly defined my career, and I am grateful to Dr. Shalev for trusting me with this responsibility.