Synthesizing EBC-46, the cancer-killing compound in rainforest blushwood fruit

A few years ago you may have seen reports of the cancer-killing blushwood fruit from the Austrailian rainforest. Injected into a tumor it provokes an inflammatory immune response. Recently, researchers at Stanford University have synthesized it from phorbol.

A good starting point for making EBC-46, Wender and colleagues realized, is the plant-derived compound phorbol. More than 7,000 plant species produce phorbol derivatives worldwide and phorbol-rich seeds are commercially inexpensive. The researchers selected Croton tiglium, commonly known as purging croton, an herb used in traditional Chinese medicine.

Wender, P.A., Gentry, Z.O., Fanelli, D.J. et al. Practical synthesis of the therapeutic leads tigilanol tiglate and its analogues. Nat. Chem. (2022). https://doi.org/10.1038/s41557-022-01048-2

News report from 2019

5-minute daily IMST lowers blood pressure as much as exercise or drugs

According to Lisa Marshall in https://www.colorado.edu/today/2021/06/29/5-minute-breathing-workout-lowers-blood-pressure-much-exercise-drugs

Working out just five minutes daily via a practice described as “strength training for your breathing muscles” lowers blood pressure and improves some measures of vascular health as well as, or even more than, aerobic exercise or medication, new CU Boulder research shows.

The study, published today in the Journal of the American Heart Association, provides the strongest evidence yet that the ultra-time-efficient maneuver known as High-Resistance Inspiratory Muscle Strength Training (IMST) could play a key role in helping aging adults fend off cardiovascular disease––the nation’s leading killer.

They used a POWERbreathe K3 inspiratory muscle training device https://www.powerbreathe.com/product/powerbreathe-k-series , but maybe even a cheap traditional breather used every day would have benefit.

Marshall also writes

Preliminary results from the same group suggest IMST also improved some measures of brain function and physical fitness. And previous studies from other researchers have shown it can be useful for improving sports performance.

and

In an editorial accompanying the journal publication, researchers not involved in the study called for more research on the myriad health benefits, including potentially mental health benefits, the practice may hold.

Hyperbaric oxygen treatments (HBOT) reverse aging in humans

According to “First clinical trial reverses two biological processes associated with aging in human cells“

A new study from Tel Aviv University (TAU) and the Shamir Medical Center in Israel indicates that hyperbaric oxygen treatments (HBOT) in healthy aging adults can stop the aging of blood cells and reverse the aging process. In the biological sense, the adults’ blood cells actually grow younger as the treatments progress.

The researchers found that a unique protocol of treatments with high-pressure oxygen in a pressure chamber can reverse two major processes associated with aging and its illnesses: the shortening of telomeres (protective regions located at both ends of every chromosome) and the accumulation of old and malfunctioning cells in the body. Focusing on immune cells containing DNA obtained from the participants’ blood, the study discovered a lengthening of up to 38% of the telomeres, as well as a decrease of up to 37% in the presence of senescent cells.

Reverse aging with therapeutic plasma exchange (TPE)

Following up to “Instead of parabiosis (infusing young blood) the cure for diseases of aging may be scrubbing old blood“, according to Kara Manke in “Diluting blood plasma rejuvenates tissue, reverses aging in mice”

A new study by the same team shows that similar age-reversing effects can be achieved by simply diluting the blood plasma of old mice — no young blood needed.

In the study, the team found that replacing half of the blood plasma of old mice with a mixture of saline and albumin — where the albumin simply replaces protein that was lost when the original blood plasma was removed — has the same or stronger rejuvenation effects on the brain, liver and muscle than pairing with young mice or young blood exchange. Performing the same procedure on young mice had no detrimental effects on their health.

This discovery shifts the dominant model of rejuvenation away from young blood and toward the benefits of removing age-elevated, and potentially harmful, factors in old blood.

Paradoxical lucidity — evidence that severe dementia might be reversible

According to Kelly Malcom in “Moments of Clarity, Glimmers of Hope: Scientists consider how unexpected awakenings in dementia patients might shed new light on the disease”

It happens unexpectedly: a person long thought lost to the ravages of dementia, unable to recall the events of their lives or even recognize those closest to them, will suddenly wake up and exhibit surprisingly normal behavior, only to pass away shortly thereafter. This phenomenon, which experts refer to as terminal or paradoxical lucidity, has been reported since antiquity, yet there have been very few scientific studies of it.

and

“We’ve assumed that advanced dementia is an irreversible neurodegenerative process with irreversible functional limitations,” […] “But if the brain is able to access some sort of functional network configuration during paradoxical lucidity, even in severe dementia, this suggests a reversible component of the disease.”

The price of wakefulness — neurons need sleep to repair DNA damage

According to Lior Appelbaum in “Sleep tight! Researchers identify the beneficial role of sleep: Sleep increases chromosome dynamics that clear out DNA damage accumulated during waking hours.”

Despite the risk of reduced awareness to the environment, animals — ranging from jellyfish to zebrafish to humans — have to sleep to allow their neurons to perform efficient DNA maintenance, and this is possibly the reason why sleep has evolved and is so conserved in the animal kingdom.

Muscle: “Use it or lose it, until you work at it again.”

According to Lawrence M. Schwartz

It is well documented in the field of exercise physiology that it is far easier to reacquire a certain level of muscle fitness through exercise than it was to achieve it the first place, even if there has been a long intervening period of detraining. In other word, the phrase “use it or lose it” is might be more accurately articulated as “use it or lose it, until you work at it again.” This has been demonstrated directly by another experiment from the Gundersen lab that demonstrated that once a muscle has acquired new nuclei, it retains them long after the hypertrophic stimulus is removed. They induced muscle hypertrophy in female mice by treating them for 2 weeks with testosterone and then examined the muscles 3 weeks after steroid withdrawal (Egner et al., 2013). Muscle volume had returned to baseline but the newly acquired nuclei persisted even 3 months later. When the muscles were subjected to overloading to reinitiate hypertrophy, the steroid-treated ones rapidly underwent a 36% increase in fiber volume while control muscles only grew by 6%. These data suggest that the “surplus” nuclei could be mobilized rapidly to facilitate retraining.

These observations have potential implications for public health policy. It has been shown that muscle growth, physiological function, and regenerative capacity all decline with age, largely due to reduced satellite cell proliferation (Blau et al., 2015). Consequently, exercise during adolescence, when muscle growth is enhanced by hormones, nutrition and a robust satellite pool, might functionally serve to allow individuals to “bank” myonuclei that could be drawn upon later in life to slow the effects of aging and possibly forestall sarcopenia.

Alzheimer’s probably caused by same bacteria as gingivitis

According to Debora MacKenzie in “We may finally know what causes Alzheimer’s – and how to stop it”

Multiple research teams have been investigating P. gingivalis, and have so far found that it invades and inflames brain regions affected by Alzheimer’s; that gum infections can worsen symptoms in mice genetically engineered to have Alzheimer’s; and that it can cause Alzheimer’s-like brain inflammation, neural damage, and amyloid plaques in healthy mice.

“When science converges from multiple independent laboratories like this, it is very compelling,” says Casey Lynch of Cortexyme, a pharmaceutical firm in San Francisco, California.

In the new study, Cortexyme have now reported finding the toxic enzymes – called gingipains – that P. gingivalis uses to feed on human tissue in 96 per cent of the 54 Alzheimer’s brain samples they looked at, and found the bacteria themselves in all three Alzheimer’s brains whose DNA they examined.

3 billion people depend on dung fuel

According to Russ George

More than 2 billion people’s lives depend entirely on dung energy. Another billion use dung as part of their energy. That’s nearly half of humanity that depends on dung.

It’s a practical available fuel, but one that creates all manner of health issues.

There does not seem to be any alternative for the nearly half of humanity that is on the wrong end of this shitty deal, or is there?

The principal victims of the world of dung burning are women as they are most exposed to the deadly fumes, high levels of dioxins and chlorophenols compared to wood, released when using of dung as fuel. The World Health Organization is worrying about the deadly fumes that accompany dung fuel but has no tools to resolve this health crisis. Dung is the cheapest of all fuels and is used mostly in rural and undeveloped areas of the world where other forms of energy are simply neither available nor affordable. Thus for upwards of a billion low-income households, dung is the most vital and widely used fuel source. It is freely available and accessible without payment or very inexpensively. Burning dung delivers about half the energy as burning wood. But there are many drawbacks.

For example, according to the WHO link above

Exposure to household air pollution almost doubles the risk for childhood pneumonia and is responsible for 45% of all pneumonia deaths in children less than 5 years old. Household air pollution is also risk for acute lower respiratory infections (pneumonia) in adults, and contributes to 28% of all adult deaths to pneumonia.

Instead of parabiosis (infusing young blood) the cure for diseases of aging may be scrubbing old blood

According to Brady Hartman

Having conducted parabiosis experiments for years, the Conboys noticed that the most significant changes occur in the younger mice in response to the old blood. These rodents became weak like their elderly counterparts. Their results suggest that it may not be factors in the young blood that are rejuvenating, but rather that old blood has pro-aging molecules. While young blood has slight rejuvenating properties, the primary goal of rejuvenation is to remove bad actors from old blood.

Therefore, a more efficient approach would be to figure out which specific factors in old blood are pro-aging and find a way to clear them from the body. This could have profound implications for the treating the chronic diseases of old age, including metabolic changes, frailty, Alzheimer’s, Parkinson’s, and other forms of dementia.

To accomplish this, the Conboys are planning a plasmapheresis process to scrub aged blood and then return it to the patient.

Or maybe more likely, medication to stop the older body from creating those factors in the first place.