Mushroom Powder and Cholesterol

 

Mushroom Powder and Cholesterol

Apparently mushroom powder as a dietary supplement is trendy. So trendy that Marks and Spencer, bastion of ‘mainstream but in touch’ now have their own range of products containing mushroom powder. ! Low fat, high in protein and fibre, mushroom powder products tick all the boxes, especially when made into a popular format such as ‘creamy shakes’.

When you search for the nutritional benefits of mushroom powders you get all the normal superfood guff but omitted is a very significant ingredient. That ingredient is called ergosterol. Ergosterol is a cholestero-genic compound, in other words it is a precursor to cholesterol. 

Like cholesterol It is readily converted to Vitamin D2 (via cholesterol) by the action of UV in sunlight, hence the availability of ‘Vitamin D enriched mushrooms’ which are pre-exposed to sunlight before sale. Another, closely related, cholestero-geneic compound is squalene found in extra-virgin olive oil. 

I just find it amusing that still living in a world that obsesses about levels of cholesterol circulating in the blood that two superfoods are exemplars of foods that increase blood cholesterol. This effect would be marvelous at increasing our Vitamin D levels if only we went out into the sunlight without factor 50 suncream to prevent it.

Oh well, it looks like cholestero-geneic diets are good for you, maybe even essential if you are on statins which stop your body making cholesterol.

ps..if you are interested, M&S mushroom products use 'Lion's Mane' mushroom powder which is particularly high in ergosterol.

UPFs gave me wagu thighs

Interesting article reproduced this week in the Financial Times from the annual meeting of the Radiological Society of North America held in Chicago. 

One group reported to the conference that in a study of 60 yr olds, whose diet consisted of approximately 40% so called UPF, but who did not consume excessive calories had ‘fatty thighs’!

They  differentiated between fat outside muscle tissue and fat within muscle tissue. In other words fat pads under the skin making the thigh look ‘fat’ and fat within the tissue itself. To those who eat meat, intramuscular fat is recognised and valued as ‘marbling’ because it enhances both taste, succulence and texture.

No hypotheses were put forward but one more nail in the UPF coffin was hammered home and it drew the usual scoff from the food industry who know that as a collective term UPFs are impossible to define…so are UPFs the bad guys here?

As a biochemist I wondered how quickly an hypothesis could be generated and how well it could be pinned to a modern UPFish diet or not..The answer was .. about 10 minutes.

The beef industry values marbling in meat the ultimate expression being in asian cattle and Wagu steaks. The adipocytes ( fat cells) within muscle are different to those outside tissue and respond to different signals most of which are poorly understood or studied. However mild injury and inflammation increases intramuscular adipocyte activity and fat infiltration in to the tissue. Some cattle are genetically disposed to intramuscular fat infiltration but other than the above the only strategy to increase marbling is to add conjugated linoleic acid to the feed. These are called CLAs and can be synthesised as well as being present in natural foods.

Natural sources of CLAs are basically: milk, cheese and meat.. The highest values I found published when a quick web search was carried out are in milk, ground beef and mozzarella cheese.

So, let me think: latte coffees, burgers and pizzas should max out our CLA intake

There you go, nothing to do with bad stuff in the foods, after all you can get the highest quality of unadulterated ingredients in all three of the foods above, but if you have a latte each day, burgers twice a week and a take away pizza, you’ll probably get wagyu-thighs!

Ps if you are wondering what the intramuscular fat is doing in your muscles, quite simply it is an energy store placed as close as possible to the muscle mitochondria which use fatty acids as slow burn fuel. Ideal for a labourer maybe not ideal for an office worker.

Senescence: time for humanity to enter the dying phase

 Time to start dying.

I have just re-read the opening paragraph to my 1979 Ph.D thesis on the Biochemistry of Ageing (Rat Mitochondria). It laid out the goal of the field of study called gerontology. In a nutshell, the goal was: ‘the extension of years of active life before entering the senescent phase’. It also said explicitly that increased life span due to prolongation of the senescent phase was a bad idea, something I feel with which few would disagree.

Unfortunately I think in the last fifty years we have achieved mostly  the latter and in the worst way. There has been an increase in UK average maximum life span ( about 3 years more for men and women) in that time but I am increasingly thinking that the senescent phase is starting earlier. 

In the UK the cost to the taxpayer of supporting the long term sick is large, increasing and unsustainable. I think a great many of this group have entered a  senescent phase, or at least a version of it. This assertion needs a lot of unpacking to sound credible.

Firstly we expect old people to look old. We readily recognise superficial phenotypes denoting ‘old’;  low energy, wrinkles, faltering gait, muscle loss, incontinence and bone fragility to name a few. Some of these such are products of deteriorating connective tissue which is a time-dependent passive chemical process rather than a reflection of physiological or biochemical ageing. Physiological changes, say to do with muscles or the brain on the other hand are under active processes. Processes we now know are ultimately mediated by mitochondria via internal and external signals

Now, the broad signals  for a cell or a body to enter a senescent phase are well known. They are DNA damage ( eg from radiation, pollution,toxins) , epigenetic ( eg onco-viral),  telomere erosion ( the ability for a cell to divide) and mitochondrial dysfunction. All except telomere erosion can be influenced by environment, diet and lifestyle.

To follow the argument in this post you need to imagine a senescent individual who does not look old. So his/her limbs and body will remain plump, skin smooth-ish, and heads hairy. They will however also be largely inactive ( low energy) and suffering from chronic inflammatory diseases like arthritis and IBS and dementia. Low immune surveillance will also lead to an increase in early onset cancers especially where inflammation is high, eg the gut. Sarcopena ( muscle loss ) will also be evident, though largely hidden by intramuscular fat. Finally, mental health issues such as depression and anxiety come to dominate cognitive processes.. In all respects characteristics of folk in teh senescent phase.

How could this happen? How did the ‘not-old’ enter a senescent phase? ‘Signals’ are received and acted upon by an organism on very many levels. For example mitochondria ‘note’ energetic demands, the amount and character of ‘food’ being delivered, the level of damage in the cell, the activity of endogenous and exogenous viruses, exposure to NIR light at dawn and dusk. The list goes on, and mitochondria proliferate or die or kill the whole cell depending on what they find.

At a more complex  level the mind responds with behavior changes according to the perception of the environment, broadly divided into good times or bad times. Bad times triggers reduction in mating and vice versa. 

As you can see in the profile of the Ist World human there are plenty of candidates to signal ‘it’s all over chums go into senescence’ .  And with very bad luck modern medicine will prolong this phase even longer. Happy days.

Dementia, shingles and statins ...pharma's biggest oops!

I have just returned from my local GP surgery for a routine check and saw a poster informing all that one

in four adults will get shingles. Excuse me! One in four? I would have queried this figure except

for the fact that amongst my 60+ peers I find shingles is, well, rampant.. and consequently

I am looking for my free shingles vaccination as soon as I turn 70.

Shingles is nasty, painful and infectious; especially to those who never had chickenpox or the chickenpox vaccination. Worse, you are not guaranteed to get better. Shingles is a bit like its relative the herpes cold sore, it is a reactivated virus acquired earlier in life. Shingles is a reactivated chickenpox virus once living quietly in nerve cells.

How is it reactivated?  The consensus is that it is a result of an immunosuppressant failure. Duh! This is restating the obvious and has no information associated with it other than some very interesting data.  Patients medicated with statins have an increased susceptibility to shingles. I am not joking.

Studies show that people who take cholesterol-lowering statin drugs are at higher risk for developing shingles. “A possible reason,” says Dr. Cohen, “is that statins may affect the immune system.”  For further info confirming this:

https://bmjopen.bmj.com/content/9/2/e022897

A wide range of viruses ranging from Herpes to Covid to  oncoviruses ( cancer causing) typically target mitochondria once they have gained entry to a cell. The reason is simple, mitochondria control cell death ( apoptosis ) and will cause the cell to commit suicide in response to infection.

Shutting down the cell, the apoptotic response to something going wrong within a cell, is an integral part of the basic immune response to infection (and indeed of the termination of cancerous cell too).

Mitochondrial morphological changes occur as virus Herpes Zoster virus reactivation progresses showing that front line defence against reactivation is being compromised.

So, readers of my posts will be already aware of what comes next:

Statin medication affects mitochondrial health through alteration of cholesterol availability. Lowered mitochondrial health sometimes  leads to apoptosis of muscle cells in some individuals ( muscle pain, sarcopenia) and in others or even the same people  lower immune surveillance of endogenous viruses such as herpes zoster, ie they get shingles.

One in four should expect to get shingles!. What are the figures for those over 60 on statins? A tsunami of statin related health outcomes are coming our way

post script: 

I have just had my shingles vaccination (the recombinant vaccine not the live vaccine) and I am v happy with this especially when a little more research informs me that the vaccine helps protect against dementia. Another 'what!!'  It seems like it does not matter if it's the live or recombinant vaccine, both work. But why? No mechanisms are proposed. 

I have a mechanism. Shingles are linked to statin use. My proposition is that the nerve cells invaded by the resurging Herpes Zoster virus are made disproportionally vulnerable by statin use ( unsuprising maybe given how much cholestrol is needed in the myelinated axon's insulation sheath)  So in the shingles v dementia findings it is simpler to see shingles as a vulnerability sympton rather than a cause of nerve deterioation. Yes, the net is closing in around statins' unforseen consequences.

We, Gen AZ are different.

  

Do you find nowadays that you ‘start a cold’ or go to bed feeling that ‘something is coming' on’ fully expecting a minor illness only to wake up with it gone? Can you remember the last time you went to bed with a bug? If not you are probably a member of Gen AZ.

‘Boomers’ plus Gens X, Y,  Z  and now A, are shorthand labels that conveniently divide the spread of population ages into chunks that facilitate ‘targeted messaging’. The letters replace terms such as  ‘old’, ‘middle aged’, young, adolescent and child which enables ‘market targeting’ to sound a bit more academic than it is really.

This post is about a very different generation..Gen AZ. Gen AZ is anyone old enough to be vaccinated against Covid 19 in the early 2020s who received the adeno-virus vaccine delivery vector designed to produce the now famous ‘spike-protein’ which in turn primed the immune system in order to fight the then deadly Covid-19 virus 

Sounds complicated? Yes indeed, it’s sufficiently esoteric to be utterly incomprehensible to non-biochemists. However incomprehensibility does not mean insignificant. Known colloquially as the ‘Oxford-vaccine’ and manufactured by Astra-Zenica only a relatively few people globally can lay claim to be GenAZ. Gen AZ  has indeed received the ultimate in ‘targeted messaging’. 

Back in the day, as they say, when Covid 19 was rampant and the race for mass, global vaccination was on, only three pharma companies understood the RNA recombinant technology and had the expertise to safely, in quantity, make an effective  Covid 19 vaccine. These were Astra-Zenica, Pfizer and Moderna. Many companies around the globe  could not do this. In Russia, China, India and Europe there were famous mega-pharma companies who simply could not master the technology. 

Of the effective new vaccines there were two types. The so-called mRNA vaccines made by Pfizer and Moderna and the Adeno-virus DNA vector made by Astra Zenica . Given the vast scale of the vaccination programmes both technologies proved to be remarkably safe as well as amazingly effective. However AZ vaccinations which dominated the initial program in the UK were soon superseded in subsequent immunization programs by either Pfzer or Moderna. For example in my own instance, as a boomer gen member in the UK, I got my first two early jabs from AZ. Subsequently I have had only Pfizer and Moderna. Friends in nearby Ireland, slightly late to the party, never got the AZ vaccination at all. AZ quietly disappeared following ‘bad reaction scares’ which in hindsight were not significant.

We, Gen AZ are different. 

Some readers may remember trolling memes emanating from Russia at the beginning of the pandemic when the announcements that the vaccines were coming brought relief and hope to millions. Crudely put the vaccines, they said, would modify our DNA and turn us into apes or something. Vaccine fear was born ‘bigly’ as the USA president at the time may have said. Even though simian traits have been displayed by many of our leaders this prophecy has needless to say not come to pass. But the trolls were right in an important way.

After Astra Zenica bowed out leaving the field to Pfizer and Moderna they moved a development  lab from their UK base to Ireland. Shortly after that, a paper from the Basedo lab at Trinity Dublin1, was published showing ‘non-target’ immunity from Gen AZ. In other words some generalized immunity to infection seemed to persist in those who had had AZ vaccine. Cue, end of trail.

Introducing attenuated and genetically modified ( ie it is engineered so that it can't reproduce) adenovirus DNA into a cell is wholly different to introducing mRNA. mRNA has a short shelf life before it is broken down and its components recycled. The fate of introduced DNA is far less certain. 

Introduced DNA may be broken down in the cell, or it may not; it may persist as free epigenetic DNA, it may be incorporated into nuclear or mitochondrial DNA; it may be repaired; it may be transcribed fully or in part to make mRNA and thence proteins identical to to alike to the ‘spike protein’. So logically it is overwhelmingly likely that Gen AZ has modified DNA.

What does this mean? Firstly I think this is the first and last time the Adenovirus vector is used en-masse and secondly Gen AV is being followed very closely. What fate is in store for chimeric Gen AZers? We’ll see.

1. https://www.irishtimes.com/health/2023/01/18/covid-wider-benefits-to-astrazeneca-vaccine-trinity-research-indicates/

https://www.tcd.ie/news_events/articles/2023/research-indicates-wider-benefits-to-astrazeneca-vaccine/

For a clear description of the methods of vaccine delivery into cells the article below from Nature is worth reading.

https://www.nature.com/articles/s41541-021-00356-x

Girls in school computing...it's a man's world

 

Mea Culpa. About twenty years ago I campaigned with others to get rid of compulsory ICT at GCSE in UK schools and replace it with computing, ( Computer Science as it would be called).  We fought bitter battles with EduGeek, the DFE, Microsoft, Research Machines (RM) and others. Good days for the Open Source world.

The reasoning was clear in that:

1) it was obvious that ICT served simply as vocational traing in the use of Microsoft Office and that the cost of MSOffice licencing in schools was a scandalous rip off, all aided and abetted by a now defunct but then powerful quango called BECTA.

2) Coding, egineering and programming skills were, as a result of the above, absent from a generation of students and that this was a 'bad thing'.

To cut a long story short, indeed ICT was dropped as a complsory subject and replaced by computing but no-one saw the Micheal Gove reforms coming! Basically GCSEs were now too easy ( by UK HM Gov Dept of Education's reckoning) and were made harder, a lot harder.

Unexpectedly having long retired I returned to school teaching in 2015 to fill a part-time vacancy for Computer Science despite being well into my sixties. Apparently the old ICT teachers were struggling and failing with computing, so duly left.

By 2017, no-one in the school was getting any ICT but oh boy was GCSE Computing tough! 

The syllabuses were not dull if you were a full on geek, full of abstractions and concepts. Interesting for a mixed class of 15 yr olds? Not at all. Could you wing you way through it? No you could not. 

Once computing became optional then although every student would acknowledge its importance in the modern world its numbers crashed. Worse it attracted a certain type ( yes we all know who we are) of student. Inevitably proportionally speaking, few of which were female. 

Today The Guardian newspaper reports that in 2023, 4 out of every 5 Computing students at GCSE are male.  

They did not have figures for A Level Computing ( really quite tough now) or university entrance numbers but it is safe to assume on past experience that the numbers of females falls proprortionately at each step. In other words, as The Guardian has worked out for itself ,the 'New World' dominated by IT and of course AI,  is overwhelmingly male.

With hinsight I regret our success in wiping out ICT, and I regret the elitist approach to computing. Sorry. Unintended consequences. Can I blame the Tories? Only for putting a narrow ideology above pragmatism and cocking up the implementation but that's not exactly a surprise to anyone in any sector in 2024.

Does it matter? Again past experience shows that when males have complete dominance over their world they create it in their image. 

Maybe that's not a good thing?

Biological AI, a unit of cognition?

Biological AI, a unit of cognition?