What are You Thinking?

A previous post (‘Blood Bath’) looked at heterochronic parabiosis, which describes the transfusion of blood from young animals to old ones and vice versa. Blood is a rich and highly bioactive soup of mediators, messengers, inhibitors and growth factors, and when drawn from a young ‘un is capable of de-ageing mice and, probably, men. 

The process has been shown to rejuvenate murine mitochondria (1, 2), blood vessels (2, 4), skeletal muscle (3), hearts (3) and central nervous systems (4 – 7).

On the basis of pre-clinical findings like these, the US company Alkahest is running clinical trials of young plasma for Alzheimer’s and Parkinson’s diseases (NCT03520998, NCT03713957, NCT03765762), macular degeneration (NCT03558061, NCT03558074), and postoperative recovery following knee or hip replacements (NCT03981419).

Additional trials are administering umbilical cord blood and plasma to treat age-associated frailty in South Korea (NCT02418013), and young plasma to improve neurologic outcomes after acute stroke in China (NCT02913183).

Young blood and plasma is easy to obtain, but it is difficult to guarantee that the red stuff is free of all viruses, prions and phages (8). Your supplier may not have too many miles on the clock, but you don’t know where he (or she) has been. The gerontocrats who run many of our institutions have therefore funded a good deal of research into isolating the key anti-ageing factors, and producing them synthetically. 

Much of this pioneering work was done at the Institute of Bioregulation and Gerontology in St Petersburg under the auspices of Col. Professor Vladimir Khavinson, a former champion boxer and track athlete, and a remarkable man by any standards.

From what I’ve been told (an old friend of mine liaises with the Institute, and I have met members of Khavinson’s team), it started with a retinal regeneration project designed to repair retinas damaged by battlefield lasers DARPA was then developing. Khavinson looked for actives in young bovine retina, and found the first of a series of tissue-trophic peptides that encouraged the growth of retina in older animals. 

This approach could be dismissed as a modern variant of the age-old (and discredited) Doctrine of Signatures (9), but it works. The results, which I have studied, are breath-taking, and prove beyond all doubt that dead retinal tissue can be reconstructed using simple peptides. But it did not stop there. The St Petersburg team went on to develop over 60 di-, tri- and tetra-peptides which are now being used to regrow / rejuvenate various tissues in adult humans. I have data sheets on 38 of these, and the overall picture is impressive. 

Pharmaconutrition is highly effective at reducing the risk of non-communicable degenerative disease, but at a certain point (ie myocardial death after a heart attack or trabecular loss in long bone), it reaches its event horizon.

That is where the St Petersburg approach takes over, and complements and extends our own (ie (11-19). Khavinson’s work worth a post all on its own, but my magpie attention is drawn, today, in a different direction. 

Downwards, you might say, and to the subject of heterochronic fecal transfer.

The gut-brain connection is real, and very important. It has been known for a decade or so that germ-free rodents have specific cognitive deficits (ie 20). It is also known that the gut microbiome changes with age (ie 21, 22), becoming less diverse (23) and probably leaving the owner less able to resist nutritional and environmental stresses (24). And as time passes, the ageing rodent’s memory and other cognitive functions start to falter; much like our own.

Might these changes be related, and if so, how? Does the faltering brain affect microbiomal change, or does the ageing microbiome drive brain ageing? It certainly contributes to many other aspects of the ageing process, and to age-related pathologies including the neurodegenerative diseases (ie 25).

In 2020 a Chinese team showed that fecal transplants from old to young rats caused cognitive decline and created the kinds of micro-anatomical changes in neuronal structure normally found in aged animals (26). The following year, an Irish group working with mice demonstrated that fecal transplants from young to old rats had the opposite effect (27), leading to improvements in working memory.

The old mice learned to solve mazes more rapidly, and were better at remembering the maze layout on subsequent attempts. Their hippocampi started to rejuvenate, becoming more physically and chemically similar to the brains of younger animals (27). 

This fits rather well with a 2021 clinical study which found that older humans who have more diverse microbiomes (and who are thought to have eaten a more varied and plant-based diet) age more successfully (28).

In this American study, health and life expectancy was significantly reduced in those whose microbiome was characterised by high levels of Bacteroides species. These gram-negative microbes occur in most anaerobic infections and are associated with significant mortality (29). Being gram negative they are also associated with increased inflammatory stress in the gut, and endotoxaemia (29, 30).

Adding prebiotic fibers to the diet of mice raises numbers of probiotic, gram-positive species such as lactobacilli and bifidobacterial. These drive down the numbers of Bacteroides, thus stopping the chronic inflammation and the endotoxaemia (30). Prebiotic fibers work in exactly the same way in humans (31). This neatly explains why humans with better diets and who consume more dietary fibers have less Bacteroides, and live longer (28).

To recap …

Many of the links between an ageing microbiome and age-related pathologies in humans involve the modern, ultra-processed diet. 

Our high-fat, low-fiber diet drives a shift from predominantly gram-positive fiber-utilising probiotic species to gram-negative proteolytic species, with a consequent reduction in anti-inflammatory post-biotics such as butyrate (32, 33) and increased chronic inflammatory stress in the gut. Increased numbers of gram-negative bacteria plus chronic inflammation equals ‘leaky gut’ and endotoxaemia (34-37). 

Endotoxaemia causes chronic inflammation everywhere (38, 39). It is a known contributor to NAFLD (39), unsurprisingly considering that venous drainage from the gut flows directly into the liver. It accelerates the ageing process everywhere else (41, 42). And, all these problems can be stopped at source, by eating more fiber.

The foundations of this idea were laid half a century ago by the redoubtable British surgeon and researcher Dennis Burkett, and his colleague Hubert Trowell (43), and substantiated more recently by major epidemiological and other research programs (ie 44, 45). So there you have it. And here, if you want, is how to have it better. 

By adding a mix of prebiotic fibers to your diet and maintaining a more youthful and less inflammatory microbiome you will have less inflammation, less endotoxaemia and less inflammageing. You will therefore live healthier and longer.

Given colonic length, transit time and the different fermentation rates of different prebiotic fibers, it would be logical to use an appropriately blended mix of different prebiotic fibers.

Next week: The Spice / Time Continuum. How the spice routes ebb and flow through our tissues, how they affect DNA and RNA, and how they rejuvenate our cells.

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