Everyone grows older, but scientists don't really understand why. Now a UCLA study has uncovered a biological clock embedded in our genomes that may shed light on why our bodies age and how we can slow the process.
Published in the Oct. 21 edition of the journal Genome Biology, the findings could offer valuable insights to benefit cancer and stem cell research.
While earlier biological clocks have been linked to saliva, hormones and telomeres, the new research is the first to result in the development of an age-predictive tool that uses a previously unknown time-keeping mechanism in the body to accurately gauge the age of diverse human organs, tissues and cell types. Unexpectedly, this new tool demonstrated that some parts of the anatomy, like a woman's breast tissue, age faster than the rest of the body.
"To fight aging, we first need an objective way of measuring it. Pinpointing a set of biomarkers that keeps time throughout the body has been a four-year challenge," said Steve Horvath, a professor of human genetics at the David Geffen School of Medicine at UCLA and a professor of biostatistics at the UCLA Fielding School of Public Health. "My goal in inventing this age-predictive tool is to help scientists improve their understanding of what speeds up and slows down the human aging process."
To create his age predictor, Horvath focused on a naturally occurring process called methylation, a chemical modification of one of the four building blocks that make up our DNA. He sifted through 121 sets of data collected previously by researchers who had studied methylation in both healthy and cancerous human tissue.
Gleaning information from nearly 8,000 samples of 51 types of tissue and cells taken from throughout the body, Horvath charted how age affects DNA methylation levels from pre-birth through 101 years. For the age predictor, he zeroed in on 353 markers linked to methylation that change with age and are present throughout the body.
Horvath tested the predictive tool's effectiveness by comparing a tissue's biological age to its chronological age. When the tool repeatedly proved accurate in matching biological to chronological age, he was thrilled — and a little stunned.
"It's surprising that one could develop a predictive tool that reliably keeps time across the human anatomy," he said. "My approach really compared apples and oranges, or in this case, very different parts of the body — including brain, heart, lungs, liver, kidney and cartilage."
While most samples' biological ages matched their chronological ages, some diverged significantly. For example, Horvath discovered that a woman's breast tissue ages faster than the rest of her body.
"Healthy breast tissue is about two to three years older than the rest of a woman's body," he said. "If a woman has breast cancer, the healthy tissue next to the tumor is an average of 12 years older than the rest of her body."
The results may explain why breast cancer is the most common cancer in women. Given that the clock ranked tumor tissue an average of 36 years older than healthy tissue, it could also explain why age is a major risk factor for many cancers in both genders.
Horvath next looked at induced pluripotent stem cells, adult cells that have been reprogrammed to an embryonic stem cell–like state, enabling them to form any type of cell in the body and continue dividing indefinitely.
"My research shows that all stem cells are newborns," he said. "More importantly, the process of transforming a person's cells into pluripotent stem cells resets the cells' clock to zero."
In principle, the discovery proves that scientists can rewind the body's biological clock and restore it to zero.
"The big question is whether the underlying biological clock controls a process that leads to aging," Horvath said. "If so, the clock will become an important biomarker for studying new therapeutic approaches to keeping us young."
Finally, Horvath discovered that the clock's rate speeds up or slows down depending on a person's age.
"The clock's ticking rate isn't constant," he explained. "It ticks much faster when we're born and growing from children into teenagers, then slows to a constant rate when we reach 20."
In an unexpected finding, the cells of children with progeria, a genetic disorder that causes premature aging, appeared normal and reflected their true chronological age.
Horvath noted that it will take additional research to dissect the precise molecular or biochemical mechanism in the body that makes his age predictor possible.
UCLA has filed a provisional patent on Horvath's age-predictive tool. His next studies will examine whether stopping the body's clock halts the aging process and whether a similar clock exists in mice.
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