A Mainstream View of the Longevity Industry

This popular science article from the AARP is representative of the sort of outsider's view of the longevity industry that is presently dominant. On the one hand, it is good that the media and advocacy organizations such as AARP are finally talking seriously about treating aging as a medical condition. On the other hand, the author looks at two of the most popular areas of development, mTOR inhibitors and senolytics, in a way that makes them seem more or less equivalent, and then further adds diet and exercise as another equivalent strategy. This will be continuing issue, I fear. People, as a rule, don't think about size of effect and quality of therapy when discussing present initiatives.

These strategies are in fact very different, and the differences are important. Clearance of senescent cells via senolytic treatments is a radically different and better class of therapy than mTOR inhibition. Senolytics remove a cause of aging in one treatment, improving all aspects of health in later life in consequence, while mTOR inhibitors must be taken continually and only encourage the aging metabolism into a state that is somewhat more resistant to the underlying damage that causes aging. Tackling underlying causes will always be more effective than trying to cope with those causes without repairing them.

"We've reached the perfect storm in aging science," says physician Nir Barzilai. "Everything is happening. We have the foundation from decades of animal studies. We're ready to move on to people." The ultimate goal: to put the brakes on aging itself - preventing the pileup of chronic health problems, dementia and frailty that slam most of us late in life. "I want 85 to be the new 65," says Joan Mannick, the chief medical officer and cofounder of resTORbio.

The need is enormous. In a decade, nearly 1 in 5 Americans will be 65 or older. Three out of 4 will have two or more serious health conditions. At least 1 in 4 can expect memory lapses and fuzzy thinking, while 1 in 10 will develop dementia. "Right now doctors play whack-a-mole with chronic diseases in older adults. You treat one, another pops up. The goal instead is to tackle aging itself, the major risk factor for almost every major disease. Our society, our drug companies and medical profession aren't addressing all this suffering that happens as people grow old. But the older people in my life are beloved to me. If we can do something about aging, we shouldn't ignore it."

Older people who took the mTOR inhibitor RAD001, a similar drug to resTORbo's RTB101, had a stronger response to a flu vaccine. Their immune systems looked younger, with fewer exhausted T cells - a depressingly common feature of aging called immunosenescence. "This was the first evidence that if you target a pathway in humans, you may actually impact how we age." The results of a trial of RTB101 were particularly strong for people 85 and older; they had 67 percent fewer infections. That's good news, because - in part due to an age-related weakening of the immune system - respiratory infections are the fourth-leading reason older U.S. adults wind up in the hospital and their eighth-leading cause of death.

Alas, there's more going wrong in older cells than on-the-fritz mTOR. Among these issues: inflammation; out-of-whack metabolism; inactive stem cells that can't repair body tissues; damage from stress, environmental toxins and free radicals; reduced "quality control," which can't eliminate rogue cells. These glitches boost the risk for everything from heart disease and stroke to diabetes, osteoarthritis, Alzheimer's disease, Parkinson's and cancer. If these and other cellular issues are the underlying causes of so many diseases, preventing cells from succumbing to them as they age is a key to preventing disease. That's why resTORbio, other biotech start-ups and university aging labs across the U.S. are launching an unprecedented number of human clinical trials with experimental compounds aimed at these mechanisms.

One big target: senescent cells that refuse to die, instead glomming up in joints and other body tissues. They pump out dozens of inflammatory compounds and other chemicals that contribute to age-related diseases. In a raft of mouse studies, clearing out these senescent cells boosted health - easing arthritis pain, improving kidney and lung function, increasing fitness, extending life and even making fur thicker. In January, the first-ever human study of a treatment to kill senescent cells in the lungs was published. Fourteen people with the fatal lung disease idiopathic pulmonary fibrosis took a mix of the drugs dasatinib and quercetin for three weeks. The verdict: The drug combo was safe, triggered just one serious side effect (pneumonia), and seemed to improve study volunteers' basic ability to stand up and walk. There were also hints it may have reduced senescent-cell activity, but the researchers say bigger, longer studies are needed.

Right now, simply staying healthy into our 80s, 90s and beyond is a lot like hitting the lottery jackpot. In a survey of 55,000 Americans age 65-plus, just 48 percent rated their health as very good or excellent. No wonder drugstores, the internet, and human history are littered with unproven rejuvenation come-ons. Meanwhile, as researchers slowly test these more legitimate drugs, what can we do today if we wish to retain good health longer? That answer has been with us all along. Not smoking, eating healthy, getting exercise, managing stress and sleep.

Link: https://www.aarp.org/health/drugs-supplements/info-2019/pill-drug-aging.html

Comments

Watched Neuralink's conference. It proves we can do a lot with a small team in a short amount of time. Aubrey de Grey could be the Musk of aging, except one is rich (investing billions on Tesla, SpaceX, Neuralink,...) and the other is not (3-4 millions yearly budget). At this point, money is everything, we already have the solution. Wonder if Neuralink could be of use to cure brain aging.

Posted by: Jonathan Weaver at July 17th, 2019 8:57 AM

Both Unity and ResTORbio have produced lackluster clinical results to date and the market views them, as of this very moment (Unity's market cap of $342MM versus ResTORbio at $370MM) about the same value proposition

The truth is until they do bigger, more comprehensive studies with definitive outcomes, we will have no idea who is a winner or a loser and what approaches will be meaningful to patients and prescribers

Posted by: David Permisov at July 17th, 2019 9:22 AM

"The truth is until they do bigger, more comprehensive studies with definitive outcomes, we will have no idea who is a winner or a loser and what approaches will be meaningful to patients and prescribers"

Nope. That would be true if we didn't know anything about biology and medicine. But actually we know a lot about them and so we can assign probabilities of success to treatment strategies with pretty good certainty. And in this case the probability is clearly favorable to senolytics with respect to mTOR inhibitors.

Some people seem to have a very strange idea about knowledge. Either you know something with 100% certainty or you know it with 0% certainty. That's absurd. The world doesn't work that way. And people don't act that way in their daily lives. They use previous knowledge to predict probable outcomes and to act accordingly. They don't treat al predictions equally until all is solved and finished.

https://xkcd.com/1132/

Posted by: Antonio at July 17th, 2019 11:29 AM

@Antonio

If your logic worked in the biopharma industry, no product would ever fail in the clinic

But that's not the way the system, or biology, ever works

Posted by: David Permisov at July 17th, 2019 12:39 PM

That's again manichean thinking. I didn't say anything like that.

Posted by: Antonio at July 17th, 2019 12:56 PM

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