“The Culprit of Aging”
By Don C. Reed
Dr. Helen Blau of Stanford is attempting something seemingly impossible: to treat aging as a disease; to lessen the devastation of old age; to recover strength, muscle mass, and endurance — for people already old.
According to Dr. Blau, a typical person past 50 will lose 10–15% of their strength every decade. But is this inevitable?
Not if a molecule called PGE2 turns out to be helpful.
When Dr. Blau gave PGE2 to old mice, it stimulated muscle stem cells and restored strength, muscle mass and endurance to their aged limbs. They ran faster and longer on the treadmill.
She also discovered a protein that breaks down PGE2, so it will not work. She called the negative protein a gerozyme, an aging associated enzyme, also known as15-PGDH,a prostaglandin degrading enzyme.
The gerozyme accumulates in muscle tissue as we age. Because the gerozyme is present in relatively higher amounts in the elderly, the availability of PGE2 decreases, which is problematic for muscle regeneration.
So, the “hero” of aging could be PGE2 (prostaglandin), and the “villain” is the gerozyme 15-PDGH (hydroxyprostaglandin dehydrogenase).
PGE2 could make muscles more powerful; 15 PDGH could wither the limbs.
Presently, Dr. Blau is working on a number of projects related to this finding. One uses PGE2 to strengthen the diaphragm, the muscle your body uses to breathe, to help COVID-19 survivors or pneumonia victims regain muscle strength lost from being on a ventilator.
A second current focus is on the neuromuscular junction- the contact between the nerve, which transmits the signal directing a muscle to move. Her group’s preliminary data suggests that elevating PGE2 levels could help restore these junctions and re-establish these key connections that are lost after injury or with aging.
There is also the possibility of alleviating sarcopenia, a systemic weakening of the muscles, afflicting about 15% of the population aged 60 yr and 30% aged 80yr, costing America hundreds of billions of dollars a year in health care. This age-related muscle loss negatively impacts the quality of life and often leads to institutionalization due to lack of mobility and loss of autonomy.
And what about sphincters? Rejuvenated muscles might include an aged urinary sphincter and aid in its recovery of strength.
Everything we do depends on muscle — if it wastes away, so do we.
Can the substance be safe for human use?
“In gel form, PGE2 is already being used in a localized treatment to induce labor during childbirth. says Blau.
I had a brief conversation with Dr. Blau recently:
Q: In your work with COVID, is the primary potential benefit a repair of weakness in the muscle wall of the diaphragm?
A: Yes, but there is more to it than that. When a person comes off a ventilator, the muscles have grown weaker through disuse. Depending on how long he/she was on the ventilator, there is a real possibility the diaphragm will simply collapse. This can be a potential risk of death. It’s a big problem with COVID, because some people have had to be ventilated for days during which time the diaphragm muscles weaken substantially. We hope that we can use PGE2 to strengthen diaphragm muscles to help mitigate the weakness that comes from being on a ventilator. This would also help increase the supply of ventilators by decreasing how long people are kept on them.
Q: Might there be a use for it in the battle against Spinal Muscular Atrophy (SMA), that deadly killer of children?
A: Yes. Any condition with muscle wasting and loss of strength might benefit. There are some promising therapeutics aimed at treating the neuron loss in SMA, but not many for muscles. Neuronal and muscle function go hand in hand.
Q: Might your therapy benefit people with Sarcopenia — overall aging-associated weakness?
A: Yes. Sarcopenia affects 15% of the population over 60. One very real fear is that the body becomes so weak with Sarcopenia and its debilitating loss of strength that the patient can’t get out of a chair and may fall and break bones in the attempt.
Our goal is two pronged — -(1) localized muscle strengthening, eg: for urinary incontinence or carpal tunnel syndrome and (2) global muscle strengthening to increase size and strength of muscles throughout the entire body.
Q: Would it be correct to say that your overall goal is to augment the function of atrophied muscle — restoring power with increased muscle mass?
A: Yes. For instance, Duchenne muscular dystrophy patients experience severe muscle wasting. We could likely mitigate some of that loss of skeletal muscle strength. We do not yet know the effects of PGE2 on the heart; we need to know that, because it is heart muscle failure from which patients die.
Q: Would there be military applications?
A: Yes, absolutely. Wounded soldiers are often bedridden for extended periods of time. It is vital that they recover strength and mobility as soon as possible, to lessen the possibility of permanent damage.
Q: You have a biotech company: Myoforte Therapeutics; what does that mean?
A: It’s a hybrid. Myo is a prefix that indicates “muscle” (Greek origin), and forte is from the Latin and signifies “strength”. Our company merged with Epirium which is filing for an IND to start clinical trials.
It is to be hoped that Dr. Blau’s work may help patients maintain strength and physical independence — combatting the one disease to which we are all subject: old age.