Is Senescence the Key to Defeating Disease and Achieving Immortality?

September 6, 2016

By WallStreetDaily.com Is Senescence the Key to Defeating Disease and Achieving Immortality?

“It was probably the single greatest moment I’ve ever experienced with them.”

So said Alan McGee, founder of independent label Creation Records, in the January/February 2007 issue of Blender. He was reflecting on the first time he heard Oasis’ career-making single “Live Forever.”

Rooted in the Rolling Stones’ uncharacteristically sunny “Shine a Light,” “Live Forever” is an upbeat, optimistic song, a direct counterpoint to the grunge that dominated the early 1990s pop culture scene.

And how prophetic it may prove to be: “You and I are gonna live forever.”

Wall Street Daily explored this territory in a July 29, 2016, article about “nanotechnology, nanorobotics and nanobots” that could help us “transcend the limitations of biology.” We emphasized three privately held “synthetic biology” companies building factories to produce designer organisms.


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Today, we’ll look at several intrepid entities leading the quest for immortality, as the idea that we may “live forever” continues to trend from the realm of the fantastic to the sense of the optimistic to the plane of the realistic.

We’ve come a long way since 1961, when, Leonard Hayflick and Paul Moorhead “discovered that human cells derived from embryonic tissues could only divide a finite number of times,” according to senescence.info.

We call this state of permanent cell-cycle arrest “senescence,” and it’s the key dynamic in the process of aging.

But we don’t know enough about it.

The National Institutes of Health (NIH) funds research into diseases such as cancer, Alzheimer’s, diabetes and other digestive and kidney diseases at about $33 billion a year.

The Obama administration has promised a $1 billion “Cancer Moonshot,” which will augment the National Cancer Institute’s $5 billion annual budget.

The National Institute of Diabetes and Digestive and Kidney Diseases, meanwhile, gets about $1.8 billion a year.

But “aging” has yet to be recognized as a major disease. So the National Institute on Aging gets only about $1.2 billion a year.

However, much of the research budget was devoted to Alzheimer’s, with the Division of Aging Biology allocated only a tiny fraction.

We call this state of permanent cell-cycle arrest “senescence,” and it’s the key dynamic in the process of aging. But we don’t know enough about it.

We know people — perhaps even family members — who suffer these afflictions. The emotional connections make it easier to justify the use of public money to fund cancer, diabetes and Alzheimer’s research projects.

But senescence may be the key to curing all of them.

Most living creatures experience “degenerative pathologies” — the loss of cellular function and tissue — as they age. It’s a debilitating process that leads to death.

Vertebrates also experience “hyperplastic pathologies.” The most deadly of these proliferating phenomena is cancer.

In contrast to the loss of function that characterizes degenerating cells and tissues, cancerous cells must acquire new, abnormal functions that allow them to develop into a lethal tumor.

Here’s where it gets interesting: Although they look like complete opposites, the degenerative and hyperplastic characteristics of aging “are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence.”

It was spelled out by Dr. Judith Campisi of the Buck Institute for Research on Aging and the Lawrence Berkeley National Laboratory in a November 2012 Annual Review of Physiology paper titled “Aging, Cellular Senescence and Cancer”:

The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action.

That’s the extremely compelling case for additional funding of aging as a disease, the cure for which may also free us from cancer.

The good news is private companies and universities are ploughing ahead with studies into the cellular aspects of aging and disease.

They’re making interesting progress, too. In fact, there are drug therapies already in trials that could significantly extend healthy human life spans.

Imagine, for example, a 60-year-old with the body of a 20-year-old.

Tests, thus far, are focused on safety, identifying possible side effects and potential for negative interactions with other drugs.

In late 2015, the Food and Drug Administration approved a trial to test whether the diabetes drug metformin could extend human life.

Metformin’s “effect on the body is to release more oxygen into cells, which is believed to increase both their durability and longevity,” writes Marty Ettington in his article for Personal Longevity. Indeed, a Cardiff University study found that diabetics on metformin live an average of eight years longer than nondiabetics. Metformin has also extended lives of lab mice by as much as 40%.

The upcoming Targeting Aging With Metformin clinical trial will include 3,000 people between the ages of 70 and 80.

Elsewhere, “According to Japan News, researchers at Keio University and Washington University in St. Louis are set to begin the first clinical trials of a compound known as nicotinamide mononucleotide (NMN),” RT reports.

Experiments on mice showed that NMN countered declines in metabolism, eyesight and glucose intolerance attendant to aging. It also activated proteins called sirtuins, the production of which ebbs as we get older. An NMN trial including 10 healthy humans started in early July.

And a December 2015 paper in the journal Cell detailed research at Harvard University that revealed a steep reduction in the functional “age” of muscle tissue achieved by treating laboratory mice with the metabolic coenzyme NAD+.

NAD+ “reversed the aging process… by increasing muscle tone and producing effects similar to eating a healthy diet and exercising. The natural process that deteriorates skeletal muscle is the same one that affects the heart,” writes IFLScience.

NAD+ levels decrease during the natural process of aging, limiting cells’ ability to produce adenosine triphosphate (ATP) in the part of the cell where respiration and energy production occur.

Levels of NAD+ in the mice had been cut in half by aging. But researchers replenished their NAD+ and rejuvenated their muscles.

Privately held Elysium Health is focusing its efforts on nicotinamide riboside (NR). NR is the foundation of Elysium’s BASIS, an over-the-counter “anti-aging” dietary supplement.

According to research conducted at the École Polytechnique Fédérale de Lausanne, NR “revitalized” stem cells, boosting cell regeneration in their muscle tissue.

Elysium’s C-suite includes veterans of Silicon Valley venture capital (VC) firm Sequoia Capital, JPMorgan’s VC coverage group and a chief scientist who also directs the Glenn Lab for the Science of Aging at MIT.

The efficacy of NR has yet to be tested in humans.

Innovative companies are also working on anti-aging therapies.

Google’s Calico Life Sciences spinoff aims “to harness advanced technologies to increase our understanding of the biology that controls life span.” Former Genentech Inc. CEO Art Levinson is running the show.

Calico also boasts former Genentech researchers Hal Barron and David Botstein on the team, as well as Cynthia Kenyon, a molecular biologist and biogerontologist who earned wide acclaim for her genetic dissection of aging in a model organism.

Calico has yet to announce any significant milestones.

But its interdisciplinary approach to the problem — its ranks include specialists in medicine, drug development, molecular biology, genetics and computational biology — as well as its strong funding base make it one to watch in the immortality space.

Finding a way to replenish stem cells will follow Human Longevity’s first goal, which is to use its massive DNA database to help identify what’s going to kill us and to find it before it does.

Craig Venter’s and Peter Diamandis’ Human Longevity Inc. is leveraging expertise in human genomics, informatics, next-generation DNA sequencing technologies and stem cell advances in another multidisciplinary approach to aging.

Venter, a biotechnologist, biochemist, geneticist and entrepreneur, was one of the first researchers to sequence the human genome.

Diamandis is an engineer and physician with an undergraduate degree in molecular genetics, a graduate degree in aerospace engineering, and an MD from Harvard.

In April 2016, Human Longevity inked a 10-year deal with AstraZeneca Plc to sequence and analyze up to 500,000 DNA samples from AstraZeneca’s clinical trials, building on what’s already the most comprehensive database of its kind.

In time, Human Longevity could develop technology that enables us to replenish the body’s population of stem cells.

Stem cells are critical to the body’s self-repair functions. They can become anything because they haven’t yet specialized into muscle or blood cells. So they can replace any cells in the body.

But our store of stem cells declines over time, and the remaining cells become increasingly worn out.

Finding a way to replenish stem cells will follow Human Longevity’s first goal, which is to use its massive DNA database to help identify what’s going to kill us and to find it before it does.

This Week In…

Envy. Writes Josh Brown in The Reformed Broker:

Why so serious? Simply put, bull markets make everyone miserable.

In a rally, when everything works to one degree or another, the need for advice or stewardship becomes lessened. It’s not a coincidence that indexers like Vanguard have captured virtually all of the inbound equity fund flows over the last few years. The value-add of most active managers becomes more apparent in down markets as stocks of cheaper valuation or superior quality shine in comparison to everything else.

If you’re doing any kind of hedging or risk management or even diversification, the longer a bull run continues, the more of a schmuck you look like. A seven-year bull market like the current one makes all responsible investors look schmucky to some extent.

For financial advisers, family officers and other intermediaries, the value of their stewardship and counsel is also much higher in difficult times. At least, the perceived value is, which is all that really counts. With risk assets near all-time highs, otherwise normally skittish clients develop temporary amnesia with regard to the help they’ve received when things were not looking quite as rosy.

There’s also performance envy, fear of missing out (FOMO) and a whole litany of cognitive issues revolving around whether or not each of us has received our fair share of the bull market. Spoiler alert: No one thinks they have, regardless of how much they’ve made.

Smart Investing,

David Dittman
Editorial Director, Wall Street Daily

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