Researchers at Penn State may have uncovered another layer of complexity in the mystery surrounding how diet influences the ageing process. A recent study, spearheaded by researchers from the Penn State College of Health and Human Development, delved into the impact of caloric restriction on telomeres – the protective caps at the ends of chromosomes composed of genetic bases.

Published in Aging Cell, the study analysed data from a two-year investigation into human caloric restriction. The findings revealed that individuals who restricted their calorie intake experienced varying rates of telomere loss compared to the control group, despite both groups ending the study with telomeres of approximately equal length. Previous research has indicated that restricting calories by 20% to 60% can contribute to extended lifespans in various animal models.

Throughout a human lifespan, each time cells replicate, some telomeres are lost as chromosomes are copied into new cells. This continual loss shortens the overall length of telomeres. Eventually, the protective cap provided by telomeres is depleted, leaving genetic information vulnerable to damage, which can hinder cellular function and reproduction. Longer telomeres indicate a younger functional age for a cell, highlighting that individuals of the same chronological age may possess different biological ages based on telomere length.

Factors such as typical ageing, stress, illness, genetics, and diet can influence the frequency of cell replication and the extent to which telomeres retain their length. Idan Shalev, associate professor of biobehavioral health at Penn State, led the team analysing genetic samples from the CALERIE study – the first randomised clinical trial of human calorie restriction. They aimed to ascertain the impact of caloric restriction on telomere length, offering insight into how this dietary intervention may decelerate ageing.

Waylon Hastings, lead author of the study and a 2020 Penn State doctoral graduate in biobehavioral health, emphasised the multifaceted mechanisms through which caloric restriction potentially extends the human lifespan. One primary mechanism involves cellular metabolism; reduced energy consumption within cells during caloric restriction leads to fewer waste products, mitigating oxidative stress and preserving cellular integrity.

The researchers evaluated telomere length in 175 study participants at the onset of the CALERIE study, after one year, and upon its conclusion after 24 months of caloric restriction. Approximately two-thirds of the participants adhered to caloric restriction, with the remaining third being the control group.

During the study, telomere loss exhibited changing trajectories. In the initial year, participants undergoing caloric restriction experienced rapid telomere loss alongside weight reduction compared to the control group. Subsequently, telomere loss slowed down during the second year as participants on caloric restriction stabilised their weight after one year. By the study’s end, both groups exhibited similar telomere lengths.

Shalev highlighted the unexpected findings, noting that while they hypothesised slower telomere loss among those on caloric restriction, the initial rapid loss followed by a slower rate was observed instead.

The results prompted numerous questions, including the potential impact of an additional year of data collection. Study participants are scheduled for a 10-year follow-up, which Shalev anticipates will provide further insights.

Despite the nuanced results, there remains promise regarding the potential health benefits of caloric restriction in humans. Previous analyses of CALERIE data have indicated potential reductions in harmful cholesterol levels and blood pressure due to caloric restriction. Although the two-year timeline did not reveal evident telomere-related benefits, further investigations may unveil them.

The research team, led by Shalev, comprised three of his trainees: Hastings, current graduate student Qiaofeng Ye, and former postdoctoral scholar Sarah Wolf. Hastings expressed gratitude for the opportunity to lead the study, acknowledging its pivotal role in shaping his career trajectory. As he prepares to embark on his role as an assistant professor in the Department of Nutrition at Texas A&M University, Hastings credits this project for providing invaluable experience in nutrition research under Shalev’s guidance.

More information: Waylon J. Hastings et al, Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis, Aging Cell. DOI: 10.1111/acel.14149

Journal information: Aging Cell Provided by Penn State