The ‘Benjamin Button’ Effect: If Scientists Can Reverse Aging in Mice, Can They Do the Same for Humans?

Fourteen years ago, the movie “The Curious Case of Benjamin Button” was released. In the movie, Benjamin Button (Brad Pitt) begins life as an elderly man in a New Orleans nursing home and ages in reverse. Twelve years later, he meets a young lady, Daisy, who flits in and out of his life as she grows older (Cate Blanchett). The hope that they might meet in the middle as they age in opposite directions, and will be together at the right time, is what helps propel this story forward. This movie about reverse aging is of course a wildly imaginative fantasy (and romantic drama), but may there come a day when reverse aging is actually possible? Maybe, because a study of reverse aging in mice was published on Jan. 12 in the journal Cell and shows that reverse aging may, to some extent, actually be possible!

For decades, scientists have believed that aging is completely genetic and stems from an accumulation of changes to DNA, primarily genetic mutations, which over time prevent more and more genes from functioning properly. These malfunctions cause cells to lose their identity, so that tissues and organs break down, leading to disease and, ultimately, death. The referenced study, based out of Harvard Medical School and led by geneticist Dr. David Sinclair, shows that aging may also be influenced by epigenetic and environmental factors that affect epigenomes (proteins and chemicals on each gene that tell the gene what to do, where to do it, and when to do it), and that the damage caused by these factors, and aging in general, can actually be reversed. Genetics focuses on how DNA sequences lead to changes in the cell, while epigenetics focuses on how DNA is regulated to achieve those changes. The main difference between genetic and epigenetic changes is that genetic changes involve changes to your actual DNA, whereas epigenetic changes do not involve a change to your DNA, but rather external changes to proteins and chemicals that affect DNA.

Study Tests David Sinclair’s Theory on Aging

To test the theory in mammals, the study involved creating temporary, fast-healing cuts in the DNA of lab mice. These breaks mimicked the ongoing damage that occurs in chromosomes that cells experience every day in response to environmental factors such as pollution, environmental toxins, and human behaviors such as smoking, eating an inflammatory diet, or suffering a chronic lack of sleep that contribute to accelerating aging.

In the study, the researchers sped the number of breaks to simulate life in fast-forward. The team also ensured that most of the breaks were not made within the coding regions of the mice’s DNA — the segments that make up genes. This prevented the animals’ genes from developing mutations. Instead, the breaks altered the way DNA is folded. Sinclair and colleagues called their system ICE, short for inducible changes to the epigenome.

As time passed, the epigenomes began to lose their original information and malfunction. The researchers saw a rise in biomarkers that indicate aging in the mice. In fact, the mice ended up with epigenomes that were more like that of older animals, and their overall health deteriorated. Within weeks, they lost hair and pigment; within months, they showed multiple signs of frailty and tissue aging.

The researchers then gave the mice a gene therapy that reversed the epigenetic changes they’d caused. The therapy delivered three genes that are active in stem cells and can help rewind mature cells to an earlier state. The mice’s organs and tissues resumed a youthful state. The therapy “set in motion an epigenetic program that led cells to restore the epigenetic information they had when they were young,” said Sinclair. “It’s a permanent reset.”

The findings point to the following:

  • Aging is a reversible process, capable of being driven “forwards and backwards at will.”
  • DNA changes are not the only, or even the main, cause of aging. Rather, the findings show, chemical and structural changes to the DNA and proteins that form chromosomes fuel aging without altering the genetic code itself.
  • There is a need for a new focus on epigenetics rather than genetics to prevent or treat age-related damage.
  • It’s important to address the root causes of aging to extend human health span: the number of years that a person remains not just alive but well.
  • Medical applications are a long way off and will take extensive experiments in multiple cell and animal models. But, Sinclair said, “scientists should think big and keep trying in order to achieve such dreams.”
  • “Our bodies hold a backup copy of our youth that can be triggered to regenerate,” said Sinclair.

“We believe ours is the first study to show epigenetic change as a primary driver of aging in mammals,” said Sinclair. “We expect the findings will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging,” said co-author Jae-Hyun Yang, research fellow in genetics in the Sinclair lab.

Sinclair Hopes the Research Helps Prevent and Eliminate Age-Related Diseases in the Future

Sinclair hopes the work inspires other scientists to study how to control aging to prevent and take it a step further and find ways to eliminate age-related diseases and conditions in humans, such as cardiovascular disease, type 2 diabetes, neurodegeneration, and frailty. “We’re talking about taking someone who’s old or sick and making their whole body or a specific organ young again, so the disease goes away,” he said.

According to Sinclair, “(i)t doesn’t matter if the body is 50 or 75, healthy or wracked with disease, once that process has been triggered, the body will then remember how to regenerate and will be young again, even if you’re already old and have an illness. Now, what that software is, we don’t know yet. At this point, we just know that we can flip the switch.”

What You Can Do to Repair Your Epigenomes

“But just as damaging factors can disrupt the epigenome, healthy behaviors can repair it,” Sinclair believes. “We know this is probably true because people who have lived a healthy lifestyle have less biological age than those who have done the opposite,” he said.

His top tips are the same tips you’ve heard over and over again. According to Sinclair, “smile and let go a little – learning to not be so hard on yourself can lead to a healthier lifestyle. Exercise, eat right, get good sleep are the top 3 ways to prevent so many diseases.”

“The message is every day counts,” Sinclair said. “How you live your life even when you’re in your teens and 20s really matters, even decades later, because every day your clock is ticking.”

For more details on the work of David Sinclair and another Oxford-educated scientist, Dr. Andrew Steele, who is also optimistic about slowing the aging process, please read my article on the subject, “Is Aging a Disease that Can be Cured?” For details on another study from a couple years ago about slowing the aging process, please read my article, “Is There Really a Drug That Reverses Age-Related Mental Decline Within Days?

As always, we strive to keep our readers updated on the research described and provide information and updates on other important research in the field of aging.

Do You Want to Live a Long, Healthy Life?

Remember, as you are eating healthy, exercising, and minimizing stress to maximize your longevity, it is also a good idea to plan for your future and for your loved ones. Our firm is dedicated to helping protect seniors by preserving dignity, quality of life, and financial security. If you have not done Incapacity Planning, Estate Planning, or Long-Term Care Planning (or had your Planning documents reviewed in the past several years), or if you have a loved one who is nearing the need for long-term care or already receiving long-term care, please call us to make an appointment for an initial consultation:

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About Evan Farr

Evan H. Farr is a 4-time Best-Selling author in the field of Elder Law and Estate Planning. In addition to being one of approximately 500 Certified Elder Law Attorneys in the Country, Evan is one of approximately 100 members of the Council of Advanced Practitioners of the National Academy of Elder Law Attorneys and is a Charter Member of the Academy of Special Needs Planners.

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