Summary: researchers at Temple University (LKSOM) announced they had found one of the body’s aging clocks in the epigenome. More importantly, they also found that calorie restriction slows the clock down. Cover Photo: Getty Images.
Imagine that human aging is governed by an internal biological clock, controlled by specific genes. If scientists could identify the specific genes that control the clock, they could develop drugs therapy that stops aging in its tracks. Perhaps even reverse it.
What Causes Aging?
Up until now, many in the aging research community weren’t sure that such a clock existed. Some thought that aging was caused by wear and tear, with the body breaking down over the decades, just as an automobile does. It seems inconceivable that any organism would engineer its own self-destruction.
Today, researchers at Lewis Katz School of Medicine at Temple University (LKSOM) have brought us one step closer to finding what makes we humans age when they announced they had found one of the body’s aging clocks in the epigenome.
More importantly, they also found a way to slow the clock down.
Publishing their discovery on September 14 in the respected scientific journal Nature Communications. The team from Temple are the first to show that the speed at which the epigenome changes with age is linked to lifespan for many species, from mice to humans.
Jean-Pierre Issa, MD, is a senior researcher in the study and Director of the Fels Institute for Cancer Research at LKSOM. Dr. Issa announced the important discovery that suggests the epigenome controls the rate of aging for nearly every mammal. Dr. Issa said that her team’s findings explain why mice live about two to three years, rhesus monkeys about 25 years, and humans about 80 years, when she said
“Our study shows that epigenetic drift, which is characterized by gains and losses in DNA methylation in the genome over time, occurs more rapidly in mice than in monkeys and more rapidly in monkeys than in humans.”
The Key To Aging
DNA methylation is a chemical modification that controls mammalian genes, telling the body when a particular gene should be used. While previous studies knew that these changes occurred with age, they didn’t know they affected lifespan. The Temple team is the first to show that the human genome plays a significant role in human aging, as Dr. Issa explains
“Methylation patterns drift steadily throughout life, with methylation increasing in some areas of the genome, and decreasing in others.”
Of Mice and Men (and Monkeys)
To carry out their research, Dr. Issa’s team collected blood from individuals of age ranges for each of the three species they tested – mouse, monkey, and human. The mice ranged in age from a few months to an elderly three years, the monkeys from less than one year to 30 years, and the humans ranged from age zero to 86 years. The researchers used human cord blood as a proxy for age zero.
The team then examined the DNA methylation patterns using deep sequencing technology. They discovered distinct patterns, with gains in methylation in older individuals occurring at genomic sites that were unmethylated in young individuals, and vice versa.
In a follow-up analysis, the team observed striking losses in gene expression in genomic regions that had become increasingly methylated with age, whereas regions that had become less methylated showed increases in gene expression.
In the third round of analyses, the LKSOM team investigated only the subset of genes affected by age-related changes in methylation. The team discovered that the greater the amount of epigenetic change – and the more quickly it occurred – the shorter the species’ lifespan.
Calorie Restriction Slows Aging
It’s no secret that cutting calorie intake can improve health and extends lifespan. While scientists haven’t waited the decades it takes to verify calorie restriction’s life-extension benefits in humans, they have found that the Fasting Mimicking Diet provides significant health benefits.
However, calorie restriction has extended lifespan in every animal tested, ranging from mice to monkeys. While scientists have known this for a nearly a century, until LKSOM’s report, we didn’t know exactly why.
Now we do.
The LKSOM Team had already shown that epigenetic changes controlled aging. The researchers weren’t satisfied with their remarkable achievement, so they set out to find ways to slow the epigenetic changes down. The researchers used calorie restriction, the most reliable intervention known to slow aging. As Dr. Issa explains “Our next question was whether epigenetic drift could be altered to increase lifespan,”
To try to stop the epigenetic drift, the LKSOM researchers cut calorie intake by 30 percent in a group of middle-aged monkeys and by 40 percent in young mice and then maintained them on the strict diet for a period. At the end of the experiment, the researchers observed significant reductions in epigenetic drift. In fact, that age-related changes in DNA methylation in the old animals on a calorie-restricted diet were comparable to those of young animals.
They had practically stopped age-related DNA methylation.
Dr. Issa had discovered exactly how calorie restriction prolongs life in animals – by slowing epigenetic drift, and concluded
“The impacts of calorie restriction on lifespan have been known for decades, but thanks to modern quantitative techniques, we are able to show for the first time a striking slowing down of epigenetic drift as lifespan increases,”
Take Home Message
Dr. Issa’s findings suggest that epigenetic drift increases aging and age-related diseases, including cancer. As Dr. Issa said
“Our lab was the first to propose the idea of modifying epigenetic drift as a way of modifying disease risk,” adding “But why epigenetic drift occurs faster in some people and slower in others is still unclear.”
In future research, Dr. Issa’s team hopes to improve upon their discovery by identifying additional factors that impact methylation drift. Through the identification of the factors, a doctor could potentially alter them, and in turn, slow down methylation drift, reducing age-related diseases and perhaps slowing down the aging process itself.
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Jean-Pierre J. Issa. Caloric restriction delays age-related methylation drift. Nature Communications, Article number: 539 (2017) doi:10.1038/s41467-017-00607-3. Published online: 14 September 2017
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