Japanese scientist Yoshinori Ohsumi just won the 2016 Nobel Prize in Physiology or Medicine “for his discoveries of mechanisms for autophagy.” Autophagy, derived from the Greek, literally means “self-eating.”
The cell is the basic building block of all living organisms.
Understanding how cells work is critical for treating and solving diseases such as cancer, diabetes, Parkinson’s, Alzheimer’s, and others that result from the process of aging.
Leonard Hayflick and Paul Moorhead discovered in 1961 “that human cells derived from embryonic tissues could only divide a finite number of times” in culture, according to João Pedro de Magalhães at Senescense.info..
This is the “Hayflick limit,” also known as cellular or replicative senescence. It’s “the key dynamic in the process of aging,” as we discussed in the September 6 Wall Street Daily issue, but we’re only scratching the surface of its implications.
Understanding how cells work is critical for treating and solving diseases such as cancer, diabetes, Parkinson’s, Alzheimer’s, and others that result from the process of aging.
We can fix deficiencies — we can, theoretically, cure death — by learning to regenerate, repair, and/or replace them.
For example, researchers at the University of Melbourne recently grew new corneal cells in a lab culture and then implanted them back into an animal’s eyes — restoring its sight.
But fundamental questions such as how a cell “knows” when it’s reached the end of its ability to divide remain open.
The good news is guys like Professor Yoshinori Ohsumi of the Tokyo Institute of Technology continue to pursue laboratory work that will help us gain the knowledge we need to overcome disease and death.
The Nobel Assembly at Karolinska Institutet awarded the 2016 Nobel Prize in Physiology or Medicine to Ohsumi “for his discoveries of mechanisms for autophagy.”
Like senescence, autophagy is a natural stress response necessary for the maintenance of cellular stability.
Autophagy — derived from the Greek word for “self-eating” — is the process by which biological cells clean themselves.
Scientific American’s Christine Gorman describes it this way: “Autophagy is the straightforward mechanism by which a cell digests certain large internal structures and semi-permanent proteins in a continual cleanup process.”
Autophagy — derived from the Greek word for “self-eating” — is the process by which biological cells clean themselves.
What was probably an evolutionary response to starvation may now hold the key to human health.
As the Nobel Assembly explained:
Thanks to Ohsumi and others following in his footsteps, we now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress. After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality-control mechanism that is critical for counteracting the negative consequences of aging.
Ohsumi expanded on work begun by Belgian biochemist Christian de Duve in the early 1960s, who “first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation.”
De Duve, who coined the term “autophagy,” won the 1974 Nobel Prize in physiology or medicine for discovering the lysosome.
More than 30 years later, Ohsumi, using baker’s yeast, isolated the genes essential to autophagy, explaining the process in the yeast context. He later demonstrated how “similar sophisticated machinery” operates in human cells too.
“His discoveries,” notes the Nobel Assembly, “opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.”
When a cell’s self-cleaning mechanism malfunctions, we see the development of diseases such as Parkinson’s and Type 2 diabetes and others related to aging. Mutated autophagy genes are linked to genetic diseases and cancer.
Researching and creating drugs and therapies based on our emerging understanding of autophagy is one of the hottest areas of biotechnology, though none have yet been developed.
It’s a tricky balance, though.
“Activating autophagy is a double-edged sword,” notes Charbel Moussa, assistant professor of neurology at Georgetown University. “One the one hand, the process clears toxic or infectious materials from cells. On the other hand, if the autophagy process goes beyond ‘recycling’ and clearing out proteins, it can start to destroy the cell, leading to cell death. “This means that autophagy must be carefully manipulated to avoid the death of nonrenewable and irreplaceable neurons.”
When a cell’s self-cleaning mechanism malfunctions, we see the development of diseases such as Parkinson’s and Type 2 diabetes and others related to aging. Mutated autophagy genes are linked to genetic diseases and cancer.
Moussa writes in the context of developing a treatment for Parkinson’s, a neurological disorder. But autophagy’s duality — the ability to destroy cellular waste and to create potentially harmful defects — cuts across a host of cancers, cardiovascular diseases, metabolism disorders, and immune-system disorders, as well.
Ohsumi is, by his own reckoning, a pretty modest scientist, focused entirely on the work and not the accolade.
As he told The Journal of Cell Biology in an interview published April 16, 2012:
Unfortunately, these days, at least in Japan, young scientists want to get a stable job, so they’re afraid to take risks. Most people decide to work on the most popular field because they think that is the easiest way to get a paper published. But I am just the opposite of that. I am not very competitive, so I always look for a new subject to study, even if it is not so popular. If you start from some sort of basic, new observation, you will have plenty to work on.
That his research could be the foundation upon which cures for cancer or solutions to aging are based is plenty ironic.
NBNBC
Here’s a breaking contrarian play. Illumina Inc. (ILMN) is a $20 billion genetic analysis company, with operations including genetic testing, genetic sequencing, gene editing, and synthetic biology.
It’s also developing a simple blood test to identify cancer in people showing no symptoms.
Management recently announced that third-quarter revenue was $607 million against prior guidance of $625 million to $630 million and a consensus forecast of $628.2 million.
In a statement, Illumina management explained: “The shortfall in quarterly revenue was driven by a larger-than-anticipated year-over-year decline in high-throughput sequencing instruments.”
So a 3% miss against Wall Street expectations had the stock down 25% at the open yesterday.
It’s a pretty good illustration of the mercurial nature of Mr. Market that one day the stock of a solid company with strong prospects in a rapidly emerging field can be worth $185 and the next day, it’s worth $139.
Smart Investing,
David Dittman
Editorial Director, Wall Street Daily
http://www.wallstreetdaily.com/2016/10/12/autophagy-self-cleaning-cells/
