Extreme heat can accelerate aging in the elderly

Just as the sun ages the skin , heat does the same with the entire organism. A study using blood samples from thousands of elderly Americans shows that those who live in areas with episodes of extreme temperatures present greater senescence at the cellular level. The work, published in Science Advances , finds that a basic molecular process of genetic expression is altered weeks and months after the heat wave. These results replicate other similar ones found with German and Taiwanese populations. The specific mechanism by which a runaway thermometer accelerates aging is not yet clear. But the accumulation of evidence, and more so in a context of climate change, forces us to place excessive heat alongside tobacco or pollution among the environmental factors that shorten life.

Few people die from heat stroke. Most of those who die from the increasingly frequent, long-lasting and intense heat waves die from something that has a somewhat macabre name: the harvest effect: people with a pre-existing medical condition or, above all, older people, who are killed by an extreme temperature event earlier than their chronological age would indicate. But, without killing, the heat may already be doing a lot of damage, especially to the bodies of relatively elderly people. Seeking to determine this, researchers from the Leonard Davis School of Gerontology at the University of Southern California (United States), analyzed blood samples from 3,686 Americans over 56 years of age.

The sample is part of a national project that follows the health status of the participants. But what interested Eunyoung Choi and Jennifer Ailshire, researchers at the Californian university, was a very specific thing: DNA methylation. This is a basic biochemical process for the body in which chemical marks are added to the DNA that function as gene switches. A few years ago it was discovered that its functioning is variable and that this variability depends on a variety of factors, among which the passage of time stands out. Today, the degree of DNA methylation is one of the main biomarkers to determine biological age, which does not always coincide with chronological age. With this information, several epigenetic clocks have been developed on which researchers rely to measure aging.

“DNA methylation is a process that regulates gene expression, i.e. it turns genes on or off without changing the genetic code itself,” explains Choi, first author of the Science Advances study. “Environmental stressors, such as heat, air pollution, and psychological stress, have been shown to influence DNA methylation patterns,” she adds. But in the case of temperatures, what is known is due to experiments with different laboratory organisms, from nematodes such as C. elegans to classic mice. “In the case of heat, prolonged exposure can trigger physiological stress responses, such as inflammation and oxidative stress, which, in turn, can cause changes in DNA methylation,” the researcher adds.

After studying the methylation patterns in the blood of the elderly in the sample using three different epigenetic clocks, the researchers placed each of the participants on a map of the United States fed with temperature and humidity data at different time ranges, from a few weeks before each series of blood draws to several months.

“Our study found that older adults living in areas with extreme heat days showed faster biological aging compared to those living in cooler areas,” Choi said in an email. Looking at the map (below), it is immediately clear that most of the counties where high temperature events occurred are concentrated in the southeastern United States, where Florida, the southern Mississippi basin, and much of Texas and the border with Mexico are located. It is in these areas that the elderly whose biological age is accelerating are concentrated. This acceleration of epigenetic age has been associated with an increased risk of chronic diseases, such as cardiovascular disease, diabetes, and mortality. However, the researcher herself recalls that “this is an observational study, which means that we cannot establish definitive causality.” Even so, Choi concludes, “the association we observed suggests that prolonged exposure to extreme heat may contribute to accelerated aging at the molecular level.”

Dr Alexandra Schneider, head of the environmental risks research group at the Helmholtz Centre Munich, Germany, was not involved in Choi and Ailshire’s work but led her own research, published in 2023. It was the first time they had found an association between medium-term exposure to heat and accelerated epigenetic ageing. They analysed the DNA methylation of 3,500 residents of the city of Augsburg and its district by taking successive blood samples and correlating them with the temperature four to eight weeks prior to the sample. As the American researchers later observed, the German team found that the higher the heat, the greater the acceleration of ageing.

“The methods used in the new study all seem valid to me. They use first-, second- and third-generation epigenetic clocks for comparison,” Schneider says in an email about Choi and Ailshire’s work. “I am not surprised by the results, since we found comparable effects in our study,” she adds, adding: “Overall, the results indicate that epigenetic acceleration of aging is a process that reinforces the often observed associations between high temperatures and mortality or age-related diseases.”

Between the work of the German and the Americans, researchers from the National University of Taiwan published in April 2024 what they consider to be the first work on the association between temperature and DNA methylation among the Han ethnic group (the Chinese themselves), which makes up around 20% of the world's population. In their case, the sample was just over 2,000 people. Again, as in the previous and subsequent work, they found a correlation between heat and accelerated biological aging. But, in their case, the sample was not limited to older people, it included participants between 20 and 70 years old, which would indicate that the harmful effect of heat would not be limited to the elderly.

The cancer epigenetics researcher at the Josep Carreras Foundation, Dr. Manel Esteller, points out that chronological age, the age determined by the date of birth, does not necessarily coincide with biological age, “as demonstrated by the ageing of smokers.” Regarding heat, he points out that there are no clues as to whether they will die earlier, “but they have aged.” He then clarifies that what is being discovered are the effects of extreme temperatures, heat peaks. In fact, two of the studies, the German one and the Taiwanese one, were carried out with populations accustomed to mild temperatures. “If you live in a torrid zone, there are adaptations,” says the scientist.

The important thing here is how much the body can adapt to rising temperatures. Studies with Spanish populations have shown a relative adaptation to heat, which would explain why fewer people die during hot summers than in past decades. But aging is another matter. Choi, the first author of the study with the elderly Americans, explains: “While we cannot rule out the possibility that some degree of adaptation may occur in populations constantly exposed to high temperatures, this does not necessarily mean that they are immune to the biological cost of chronic and extreme exposure to heat.”

Like Esteller, his colleague, Dr. José Ignacio Martín-Subero, head of the IDIBAPS biomedical epigenomics group at the Hospital Clínic in Barcelona, ​​recalls that “exposure to extreme heat does not necessarily mean that you will live less, but you are more vulnerable.” What stands out about this work is that, along with the previous ones, it adds heat to the “catalogue of environmental factors that, like tobacco, age us and knowing this catalogue, but also that of the factors that rejuvenate us, allows us to make decisions about how we want to live.”