California researchers develop drug cocktail that reverses aging — results 'remarkably promising'

Scientists find promising results in trial to reverse biological aging.

California researchers develop drug cocktail that reverses aging — results 'remarkably promising'
Photo credit: Diana Spatariu on Unsplash
  • Volunteers given a mix of three drugs "aged backwards," shedding 2.5 years off their biological ages.
  • The research focused on marks on their DNA and epigenetic clock.
  • Scientists need to continue this research with a larger population size for their next trial.

A recent minor clinical study in California suggests that for the first time ever, it may be possible to reverse the body's biological epigenetic clock.

Over the course of a year, nine healthy participants were given a mixture of three common drugs, which included a growth hormone and two diabetes medications. On average, it was found that 2.5 years of their biological ages had been shed after analyzing their genomes. Additionally, their immune systems showed signs of rejuvenation.

The results surprised researchers, but the scientists cautioned that these findings are only preliminary as the trial wasn't large enough and didn't have a control group.

Reversal of biological aging study

Clinical researchers tested the blood samples taken from the trial in order to review the reversed aspects of human aging. The significant reversal in their epigenetic ages was astounding. While they'll need to follow this study with more rigorous and large scale trials in the future, they still remain optimistic that a person's biological age can be reversed.

Their findings were published in the research journal Aging.

The authors stated that,". . . epigenetic age does not measure all features of aging and is not synonymous with aging itself, it is the most accurate measure of biological age and age‐related disease risk available today."

The results of their study put forth preliminary evidence that regression of multiple areas and markers of aging will be one day be possible for humans. The researchers write:

"The present study now establishes highly significant evidence of thymic regeneration in normal aging men accompanied by improvements in a variety of disease risk factors and age‐related immunological parameters."

What is epigenetic age?

The epigenetic clock is based off of the body's epigenome, which is comprised of the chemical modifications that occur and tag DNA, usually found on methyl groups. Patterns of these tags change during your life as you age. Scientists use these markers to track a person's biological age, sometimes they either exceed or fall behind someone's chronological age.

Scientists create epigenetic clocks by selecting certain sets of DNA-methylation site across a person's genomes.

The latest trial was created in order to test whether growth hormone could be safely used to restore human tissue in the thymus gland, this has already successfully been done in trials on dogs and rats.

The thymus gland is located in the chest between your lungs and breastbone. It serves a crucial function for the immune system. White blood cells that are produced in bone marrow mature inside the thymus, where they turn into T cells that help fight infection. This gland begins to gradually shrink after puberty.

Evidence from previous animal trials and some small human studies have suggested that the growth hormone can regenerate the thymus. However, growth hormone can also produce diabetes.

This is why the trial added two anti-diabetic drugs in the reversal aging cocktail, which consisted of dehydroepiandrosterone (DHEA) and metformin.

A scientific first that requires further investigation

University of California Los Angeles (UCLA) geneticist, Steve Horvath, one of the researchers involved in the study and a pioneer in the human aging epigenetic research told the journal Nature that he was surprised by the results.

"I'd expected to see slowing down of the clock, but not a reversal. That felt kind of futuristic," he said. "This told me that the biological effect of the treatment was robust." The effect stayed in the participants blood samples some six months after the trial was finished.

The authors wrote, ""Epigenetic 'clocks' can now surpass chronological age in accuracy for estimating biological age. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention."

According to the researchers, further studies must be conducted to fully confirm and build on these findings. They've found that as the thymus shrinks in older aged individuals, critical immune cell populations result in the collapse of T-cell receptors (TCR). This connects with and leads to most causes of death in the elderly, which include age-related increases in cancer, lowered immunity to infectious diseases, autoimmune disorders and more.

The study's authors end on a final note that, "Although much more remains to be done. The general prospects for meaningful amelioration of human aging appear to be remarkably promising."

U.S. Navy controls inventions that claim to change "fabric of reality"

Inventions with revolutionary potential made by a mysterious aerospace engineer for the U.S. Navy come to light.

U.S. Navy ships

Credit: Getty Images
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Meet Dr. Jennifer Doudna: she's leading the biotech revolution

She helped create CRISPR, a gene-editing technology that is changing the way we treat genetic diseases and even how we produce food.

Courtesy of Jennifer Doudna
Technology & Innovation

This article was originally published on our sister site, Freethink.

Last year, Jennifer Doudna and Emmanuelle Charpentier became the first all-woman team to win the Nobel Prize in Chemistry for their work developing CRISPR-Cas9, the gene-editing technology. The technology was invented in 2012 — and nine years later, it's truly revolutionizing how we treat genetic diseases and even how we produce food.

CRISPR allows scientists to alter DNA by using proteins that are naturally found in bacteria. They use these proteins, called Cas9, to naturally fend off viruses, destroying the virus' DNA and cutting it out of their genes. CRISPR allows scientists to co-opt this function, redirecting the proteins toward disease-causing mutations in our DNA.

So far, gene-editing technology is showing promise in treating sickle cell disease and genetic blindness — and it could eventually be used to treat all sorts of genetic diseases, from cancer to Huntington's Disease.

The biotech revolution is just getting started — and CRISPR is leading the charge. We talked with Doudna about what we can expect from genetic engineering in the future.

This interview has been lightly edited and condensed for clarity.

Freethink: You've said that your journey to becoming a scientist had humble beginnings — in your teenage bedroom when you discovered The Double Helix by Jim Watson. Back then, there weren't a lot of women scientists — what was your breakthrough moment in realizing you could pursue this as a career?

Dr. Jennifer Doudna: There is a moment that I often think back to from high school in Hilo, Hawaii, when I first heard the word "biochemistry." A researcher from the UH Cancer Center on Oahu came and gave a talk on her work studying cancer cells.

I didn't understand much of her talk, but it still made a huge impact on me. You didn't see professional women scientists in popular culture at the time, and it really opened my eyes to new possibilities. She was very impressive.

I remember thinking right then that I wanted to do what she does, and that's what set me off on the journey that became my career in science.

CRISPR 101: Curing Sickle Cell, Growing Organs, Mosquito Makeovers | Jennifer Doudna | Big Think www.youtube.com

Freethink: The term "CRISPR" is everywhere in the media these days but it's a really complicated tool to describe. What is the one thing that you wish people understood about CRISPR that they usually get wrong?

Dr. Jennifer Doudna: People should know that CRISPR technology has revolutionized scientific research and will make a positive difference to their lives.

Researchers are gaining incredible new understanding of the nature of disease, evolution, and are developing CRISPR-based strategies to tackle our greatest health, food, and sustainability challenges.

Freethink: You previously wrote in Wired that this year, 2021, is going to be a big year for CRISPR. What exciting new developments should we be on the lookout for?

Dr. Jennifer Doudna: Before the COVID-19 pandemic, there were multiple teams around the world, including my lab and colleagues at the Innovative Genomics Institute, working on developing CRISPR-based diagnostics.

"Traits that we could select for using traditional breeding methods, that might take decades, we can now engineer precisely in a much shorter time."
DR. JENNIFER DOUDNA

When the pandemic hit, we pivoted our work to focus these tools on SARS-CoV-2. The benefit of these new diagnostics is that they're fast, cheap, can be done anywhere without the need for a lab, and they can be quickly modified to detect different pathogens. I'm excited about the future of diagnostics, and not just for pandemics.

We'll also be seeing more CRISPR applications in agriculture to help combat hunger, reduce the need for toxic pesticides and fertilizers, fight plant diseases and help crops adapt to a changing climate.

Traits that we could select for using traditional breeding methods, that might take decades, we can now engineer precisely in a much shorter time.

Freethink: Curing genetic diseases isn't a pipedream anymore, but there are still some hurdles to cross before we're able to say for certain that we can do this. What are those hurdles and how close do you think we are to crossing them?

Dr. Jennifer Doudna: There are people today, like Victoria Gray, who have been successfully treated for sickle cell disease. This is just the tip of the iceberg.

There are absolutely still many hurdles. We don't currently have ways to deliver genome-editing enzymes to all types of tissues, but delivery is a hot area of research for this very reason.

We also need to continue improving on the first wave of CRISPR therapies, as well as making them more affordable and accessible.

Freethink: Another big challenge is making this technology widely available to everyone and not just the really wealthy. You've previously said that this challenge starts with the scientists.

Dr. Jennifer Doudna: A sickle cell disease cure that is 100 percent effective but can't be accessed by most of the people in need is not really a full cure.

This is one of the insights that led me to found the Innovative Genomics Institute back in 2014. It's not enough to develop a therapy, prove that it works, and move on. You have to develop a therapy that actually meets the real-world need.

Too often, scientists don't fully incorporate issues of equity and accessibility into their research, and the incentives of the pharmaceutical industry tend to run in the opposite direction. If the world needs affordable therapy, you have to work toward that goal from the beginning.

Freethink: You've expressed some concern about the ethics of using CRISPR. Do you think there is a meaningful difference between enhancing human abilities — for example, using gene therapy to become stronger or more intelligent — versus correcting deficiencies, like Type 1 diabetes or Huntington's?

Dr. Jennifer Doudna: There is a meaningful distinction between enhancement and treatment, but that doesn't mean that the line is always clear. It isn't.

There's always a gray area when it comes to complex ethical issues like this, and our thinking on this is undoubtedly going to evolve over time.

What we need is to find an appropriate balance between preventing misuse and promoting beneficial innovation.

Freethink: What if it turns out that being physically stronger helps you live a longer life — if that's the case, are there some ways of improving health that we should simply rule out?

Dr. Jennifer Doudna: The concept of improving the "healthspan" of individuals is an area of considerable interest. Eliminating neurodegenerative disease will not only massively reduce suffering around the world, but it will also meaningfully increase the healthy years for millions of individuals.

"There is a meaningful distinction between enhancement and treatment, but that doesn't mean that the line is always clear. It isn't."
DR. JENNIFER DOUDNA

There will also be knock-on effects, such as increased economic output, but also increased impact on the planet.

When you think about increasing lifespans just so certain people can live longer, then not only do those knock-on effects become more central, you also have to ask who is benefiting and who isn't? Is it possible to develop this technology so the benefits are shared equitably? Is it environmentally sustainable to go down this road?

Freethink: Where do you see it going from here?

Dr. Jennifer Doudna: The bio revolution will allow us to create breakthroughs in treating not just a few but whole classes of previously unaddressed genetic diseases.

We're also likely to see genome editing play a role not just in climate adaptation, but in climate change solutions as well. There will be challenges along the way both expected and unexpected, but also great leaps in progress and benefits that will move society forward. It's an exciting time to be a scientist.

Freethink: If you had to guess, what is the first disease you think we are most likely to cure, in the real world, with CRISPR?

Dr. Jennifer Doudna: Because of the progress that has already been made, sickle cell disease and beta-thalassemia are likely to be the first diseases with a CRISPR cure, but we're closely following the developments of other CRISPR clinical trials for types of cancer, a form of congenital blindness, chronic infection, and some rare genetic disorders.

The pace of clinical trials is picking up, and the list will be longer next year.

Ancient megalodon shark was even bigger than estimated, finds study

A school lesson leads to more precise measurements of the extinct megalodon shark, one of the largest fish ever.

Megalodon attacks a seal.

Credit: Catmando / Adobe Stock.
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