Has the science of anti-aging caught up with the dream of a longer life? | PharmaVoice

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Those looking to stave off the effects of aging will try just about anything, from calorie restriction and cold water plunges to vigorous exercise, and supplements. But billionaires and top scientists are betting on biotechs to find the fountain of youth.

Jerry McLaughlin, CEO, Life Biosciences
Permission granted by Life Biosciences

In the past few years, companies focused on increasing human longevity or reversing age-related diseases have cropped up, backed by big dollars and big names. 

Among them is Altos Labs, with $3 billion in funding from backers that include billionaires Jeff Bezos of Amazon and Israeli business magnate Yuri Milner. And then there’s Retro Biosciences, which pulled in $180 million from OpenAI founder Sam Altman, as well as companies like Calico Labs, Life Biosciences, and most recently Clock Bio — which came out of stealth in August with $4 million in funding and who have also seen sizable investments. 

“I’ve definitely seen the market change, just in the little over two years I’ve been involved in this space,” said Jerry McLaughlin, CEO at Life Biosciences, a company targeting the biology of aging to treat age-related diseases.

While the idea of unwinding changes wrought by age isn’t new, what has progressed is the science, McLaughlin said, pointing out that the industry is reaching a tipping point. 

“Now we have the ability to identify that aging is not just random wear and tear,” McLaughlin said. “There are biological changes that make our bodies more susceptible and likely to contract diseases or injury, and we can target those biologically — that’s the big difference.”

That promise drives a market that could reach $64 billion by 2026, by some estimates. Looking ahead, will these research-heavy upstarts be able to deliver?

“We’re no longer talking about symptomatic treatment of disease. That, to us, would be a disappointment — we’re focused on reversing disease and preventing disease.”

Jerry McLaughlin

CEO, Life Biosciences

New approaches to aging

Science has already succeeded in dramatically lengthening the human lifespan. In 1900, the average life expectancy hovered around the late 40s as people often succumbed to diseases such as pneumonia, gastrointestinal disease, flu and tuberculosis. Life expectancy grew over the next century thanks to public health and sanitation efforts, antibiotics and vaccines. 

In 2023, people in the U.S. have a life expectancy closer to 80, although it has ticked down in the past few years due to the pandemic and ongoing opioid epidemic. People more commonly die from age-related diseases like heart disease and cancer, and pharmaceutical advances continue to help people live longer. 

One 2022 study, which looked at data from 26 high-income countries, found that traditional pharmaceutical innovations continued to nudge up longevity between 2006 and 2018. Countries that approved more new drugs also saw increases in longevity. These gains were made primarily among those with higher education levels, who were more likely to use newer drugs.

Increasing health and longevity

This new batch of biotechs has loftier goals. Leaders at Clock Bio said their goal is to increase the human lifespan by two decades, and Retro Biosciences aims to tack on 10 years. Others, like Life Biosciences, haven’t laid out lifespan goals, but set out to target the biological drivers underlying age-related diseases. 

“We’re no longer talking about symptomatic treatment of disease,” McLaughlin said. “That, to us, would be a disappointment — we’re focused on reversing disease and preventing disease.”

Life Biosciences is employing two strategies: epigenetic reprogramming and chaperone-mediated autophagy. Other companies are exploring similar avenues. 

“I think where you’re seeing the greatest interest and probably what’s capturing the most excitement — and we feel fortunate that we’re playing in this space — is partial epigenetic reprogramming,” McLaughlin said. “The concept is that as we age, our epigenome, which dictates the expression of genes, is altered by environmental factors [and] by diseases like obesity and diabetes.”

Epigenetic editing aims to reverse those changes using a safer and more precise form of gene therapy that modifies gene expression using the epigenome, a system of marks that provide instructions for how DNA is read and used, without changing the underlying genetic sequence. Life Biosciences is looking to modify the epigenome of older animals to mirror that in younger animals through the expression of three of four Yamanaka factors. These are called OCT4, SOX2, and KLF4 (OSK) and named after Shinya Yamanaka, who discovered that some mature cells could be changed back to pluripotent stem cells. The fourth factor is left untouched to prevent a potential side effect, tumor formation.

The second strategy, chaperone-mediated autophagy (CMA) is used to speed clearance of cellular debris, which slows down as people age, leading to cellular dysfunction. The company’s preclinical work revealed that CMA compounds have been effective in models of Alzheimer’s disease, frontotemporal dementia and retinal degeneration.

Testing the technology

While Life Biosciences’ focus isn’t necessarily on extending life, adding years could be a welcome byproduct of curing age-related diseases. McLaughlin said that staying grounded in science could help carry new treatments over the finish line.

“I think you can have those long-term broader goals, but initially in terms of proving the concept and achieving indications, I think it’s confronting the reality of the current regulatory and reimbursement environment,” McLaughlin said. “It’s ensuring that you can develop a therapeutic that can help patients and [also] receive approval from regulatory authorities.”

“The opportunity we have to rejuvenate cells that are aged and injured to a more youthful and healthy state is something I never would have thought possible a decade ago.”

Jerry McLaughlin

CEO, Life Biosciences

Life Biosciences achieved a major milestone when they restored vision in non-human primates with a condition called non-arteritic anterior ischemic optic neuropathy — essentially a stroke in the back of the eye. The trial marked a big step up from mice because primates’ eyes are very similar to humans.

“It was a big test,” he said, noting that the results exceeded expectations, even though more challenges lie ahead. 

“Now we’re moving into an IND-enabling-studies and expect to be in the clinic in 2025,” McLaughlin said. “But simultaneously, we are already exploring additional organs and tissues.”

With all this progress, how long will it be until patients might benefit?

“I prefer not to get into the prediction game, but I think as we advance and expect to be in the clinic in 2025, one could foresee in the next five-plus years that therapeutics could be available that are targeting specific age-related diseases, but are also targeting the underlying biology of aging,” McLaughlin said, adding that in the next 15 to 20 years, the applications could expand further. “I think the future is really intriguing because we continue to uncover and learn more about the biology and our ability to manipulate it.”

While these technologies still have a long way to go, McLaughlin is hopeful. 

“The opportunity we have to rejuvenate cells that are aged and injured to a more youthful and healthy state is something I never would have thought possible a decade ago,” he said. “And not only is it possible, but we’re demonstrating it today in higher-level species — and I really look forward to, in the near term, demonstrating this in human clinical trials.”

This content was originally published here.

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