Recent Media Attention Given to the Development of Means to Treat Aging

The recent announcement of a new approach to selective forcing self-destruction via apoptosis in senescent cells, and the prospects of using it as a therapy to reverse the accumulation of such cells and their contribution to aging, produced a wave of attention from the mainstream media. As is usually the case, little of that attention was well-informed or particularly discriminating when it came to the large differences in expectation value for potential ways to intervene in the aging process. When it comes to impact on age and age-related disease, clearing senescent cells is in a completely different category from, say, calorie restriction and calorie restriction mimetic drugs, but you wouldn't know that if your only source of information is the press.

Aging is caused by accumulated molecular damage of various sorts, damage that occurs as a side-effect of the normal operation of cellular biochemistry. That damage then causes secondary and later forms of damage and dysfunction, a growing chain of cause and consequence that ends with age-related diseases and death. Broadly speaking, there are two approaches to aging as a medical condition. The first, and by far the most common approach is to tinker with the operation of metabolism in order to modestly slow down the accumulation of damage - such as via replicating the calorie restriction response shown to lengthen life in short-lived species. This typically involves drug discovery and mapping cellular biochemistry in search of points at which to intervene, the latter of which is an enormously expensive and slow process. The research community doesn't have anywhere near the level of understanding needed to proceed rapidly in this effort, and this is well illustrated by the past two decades spent in search of ways to safely mimic the calorie restriction response. There is very little of practical use to show for that yet, despite the enormous outlay in time and funding.

The second approach is to repair the molecular damage that is the root cause of aging. Unlike the full extent of cellular biochemistry in metabolism and aging, that damage is well cataloged and well understood - what isn't known are the full details of how it interacts to cause specific manifestations of aging. That knowledge isn't needed in order to produce meaningful outcomes, however. To the extent that funding can be found, the work of repairing this damage could move ahead rapidly. Unfortunately, outside a few areas such as amyloid clearance in Alzheimer's disease and some portions of the stem cell field, this isn't a majority concern in the research community. Even senescent cell clearance, now a very exciting area with a great deal of venture funding for commercial development, was a poorly funded backwater as recently as six years ago. Unfortunately, that is presently the position for other equally important areas of repair, such as clearance of cross-links that damage elasticity in blood vessels and other tissues. There remains a great deal of work to do in order to give repair of the causes of aging the prominence it merits.

The search to extend lifespan is gaining ground, but can we truly reverse the biology of ageing?

It was once a fringe topic for scientists and a pseudo-religious dream for others. But research into the biology of ageing, and consequently extending the lifespan of humans and animals, has become a serious endeavour. The true promise of ageing research is that rather than tackling individual diseases one at a time, a single drug would treat all the diseases that arise in old age, at once. The idea of extending human life makes some uneasy, as preventing death seems unnatural. But this is already happening. Drugs and interventions developed over the past century that have almost doubled human life expectancy could be considered as anti-ageing. But when we talk about an anti-ageing pill, we mean one that targets the process of ageing itself. There is already a list of such drugs shown to extend the lives of lab animals. Many of these work through mimicking the effects of a near starvation diet.

Calorie restriction has for over 80 years been the most well-studied intervention known to delay ageing. The willpower required to maintain a near starvation diet for an entire lifetime is beyond most. But regular, short term calorie restriction has strong benefits for metabolic health. Animal studies show a reliable extension in lifespan during intermittent fasting. Early on, the effectiveness of restricting calories led scientists to hunt for genes that mediated these effects, but the long-term effects of restricting calories on ageing in humans have yet to be fully characterised, and such a study in humans would be difficult to perform.

Another anti-ageing strategy is one called "senolysis": that is, killing off old and damaged or "senescent" cells. These cells take up space, grow larger, and release substances that cause inflammation. When mice are genetically engineered so that it is possible to kill off senescent cells, health is drastically improved and animals live 20 to 30% longer. The hunt is now on for "senolytic" drugs, which can selectively kill off senescent cells. One company, UNITY Biotechnology, recently raised US$116 million to achieve this.

Are You Rich Enough To Live Forever?

The California Health and Longevity Institute (CHLI) is a combination spa, medical clinic, fitness center, and research institution founded in 2006 by David Murdock, a 93-year-old billionaire who made a fortune in real estate and later bought the Dole Foods company, and who has something of an obsession with increasing his time on this earth through the combination of science and lifestyle choices. His successors are numerous. Oracle co-founder Larry Ellison, who has said that "death never made any sense to me," has spent $430 million on anti-aging research; Google founders Sergey Brin and Larry Page launched Calico, a secretive company that's seeking to extend lifespan through genetic research and drug development. Ex-financier and philanthropist Michael Milken is funneling money toward speeding up the development of drugs and other medical treatments for the chronic diseases associated with aging, and Jeff Bezos has just invested in a company called UNITY Biotechnology that is "targeting cellular mechanisms at the root of age-related diseases."

Meanwhile, PayPal co-founder and early Facebook investor Peter Thiel's Breakout Labs funds companies trying to extend the useful life of various body parts; Thiel himself has reportedly given millions to a foundation aiming to increase the human life-span. I wondered aloud why anti-aging research is happening in such concentration around the city and why so much of it is funded with tech money. "I think there's a fundamental optimism here that doesn't exist in other places. Silicon Valley is full of the kind of people who think that being rejected 43 times is not a reflection of their likelihood of success." That's precisely the attitude required to believe that death can be forestalled, or even foiled.

At the Buck Institute 180 scientists work to develop therapies to slow aging. One of them is Judith Campisi, a cancer researcher who, years back, began studying senescent cells-cells that have stopped dividing. Initially senescence wasn't thought of as bad but rather as the alternative to cells becoming cancerous. But she started to think the people in her field had it all wrong-that senescent cells were dangerous because they were oozing yucky stuff that caused inflammation in the body. (One of the hallmarks of aging is that the body carries around more inflammation, which is a major factor in, if not the cause of, age-related diseases, including cancer and heart and liver disease.) Senescent cells, Campisi and colleagues found, were essentially polluting their neighbors, causing time's ravages. Last year Campisi helped found UNITY Biotechnology, a lifespan-enhancing biotech firm in San Francisco that had received $20 million in financing even before Jeff Bezos jumped in. "We're trying to devise ways now to tame that secretory characteristic of the cell. The other next step is to make them go away."

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