GET WELL SOON

A hot button report was recently issued by the UK’s Chief Medical Officer. Bacteria or viruses, it explained, can kill long after they have left the building (1). In older persons, the inflammatory and other stresses caused by an infection can resurface up to a year later as accelerated cognitive decline (2), or a fatal stroke (3) or heart attack (4).

Oldsters are more at risk of getting an infection, and more at risk of delayed or late-stage death, for several reasons. The immune system generally becomes less competent with age, the metabolic strain of an infection is superimposed on increasingly compromised physiological systems, and older people with multiple morbidities are more often exposed to the plague pits we call hospitals.

How many of these factors are intrinsic? Could any of them be modified? And if so, how?

Chronic inflammation, now successfully embedded in most modern communities thanks largely to the onslaught of modern foods, is a major driver of cellular senescence (5). Senescent cells pump out inflammatory compounds (the Senescence-Associated Secretory Phenotype or ‘SASP’) which have anti-cancer properties, but also drive chronic inflammation (6). This creates a feed-forward pro-inflammatory loop which disorganizes and then degrades healthy tissue in multiple organs, and is a major component of the overall ageing process.

When this feed-forward loop affects the immune system, it causes immunosenescence (7). It damages (‘exhausts’) T-cells so that they become less efficient at fighting off infections (8). It also contributes to involution of the thymus (9) where the T cells are formed, reducing total T-cell counts and skewing T-cell sub-populations (10).

Inflammation plays a continuing role here. Thymic involution is driven by remodeling of the ECM that provides the structure of the organ, and that remodeling is, as commonly occurs in ageing, a consequence of chronic inflammation (11).

Unsurprisingly, thymus health, structure and function are degraded by obesity and smoking (12, 13), modifiable and pro-inflammatory lifestyle factors which increase the risk of infections and reduce both health and life expectancy (14, 15)

As the thymus decays naïve T-helper cells (crucial for fighting new infections) decline, enabling more lingering low-level and other infections – which trigger inflammation. At the same time auto-reactive T-cells increase, adding yet another spin to the inflammatory cycle (16).

The chronically inflamed and simultaneously pro-inflammatory immune system (13, 16) now starts to runs down the clock, or clocks (17). The typical age-related changes in immune cell composition and functionality increase the risk of infections, and chronic infections in turn accelerate immunosenescence (18).

This vicious cycle is associated not only with increasing vulnerability to infection, but also increasing rates of cancer, autoimmune and other degenerative diseases, declining health and finally death.

But, but … but if chronic inflammation is at the core of immunosenescence, then damping chronic inflammation should slow the ageing of the immune system, and the ageing process in general. In fact, by preventing chronic inflammation, one might hope to shift the immune system from a vicious to a virtuous cycle in which the standard age-related decline towards immunosenescence is slowed, perhaps even prevented. And if this did slow thymus involution then a host of other benefits would likely emerge including less cancer, and increased health and life expectancy (19, 20).

There is evidence that this may indeed be possible.

Immunosenescence does not occur evenly; many older individuals retain good immune function, showing immune parameters comparable to younger people. There are likely genetic factors involved here, but there are clearly environmental factors also (ie 12, 13).

Recent research suggests that lifestyles which are broadly anti-inflammatory via dietary components (21-23) and/or moderate levels of physical activity (22) delay immuno-senescence. This all seems quite logical. Innate immune-primers are probably involved too.

The immune-primer concept comes from specific research focusing on very elderly healthy individuals, aka super-agers. One recent small-scale study (24) found not only genetic signatures in super-agers related to metabolic control, longevity and better DNA repair; but also shifts in immune cell counts, and more specifically an increased proportion of B cells.

One explanation for this might be that the successful old folk had encountered and defeated more pathogens during their lives. This is what the researchers thought, but there is another possible explanation; they might have been consuming more immune-primers.

B cells (for Beginners) produce antibodies which neutralize pathogens like bacteria and viruses. They identify invaders via receptors on their surface and once activated, differentiate into plasma cells that secrete antibodies and memory B cells that provide long-term immunity.

Running the gamut of multiple infections is a potentially problematic way of exercising your B cells. Alternatively, you can simply and safely increase your intake of 1-3, 1-6 beta-glucans.

These molecules, best obtained from the cell walls of yeast such as Saccharomyces cerevisiae (brewer’s or baker’s yeast), are natural immune-primers and immunomodulators. They act as pathogen-associated molecular patterns (PAMPs), and alert / prime the immune system. Their critical importance is revealed by the fact that they are identified by no fewer than 7 classes of receptors on our immune cells (25-27), which respond to beta-glucans in multiple and highly functional ways.

Neutrophils and macrophages, for example, respond by clearing pathogens more effectively, thus improving resistance to infection (26). B cells are also activated, and respond by differentiating and then increasing antibody production (ie 27).

Much of this work is pre-clinical, and it is rather promising. In elderly rats, for example, there is limited but convergent evidence that the overall impact of these beta glucans is to reverse aspects of immunosenescence. Effectively, they restore younger immune responses (28).

There are also a few clinical trials showing B cell enhancement. One of these, carried out by Oslo-based CRO Link Medical Research, seems particularly relevant; after a 6-week course of beta glucans, circulating B-cell counts were significantly increased in elderly subjects (29). I am fairly confident that the B cell effects would have been detectable sooner, but the team were also looking at other outputs which necessitated a longer period of study.

Yeast-derived beta glucans were, until about a half century ago, omnipresent in our diets. A series of industrial and technical innovations then progressively removed these important and atypical micronutrients (26). This contributed to the appalling increase in allergy that occurred over that same time period (26) and, I believe, falling B cell counts.

It would be difficult to prove this. 50 years ago, the technology used to measure differential T and B cell counts didn’t exist, and we have no way of knowing if the shifts in immune cell populations seen in older individuals today also occurred in 1960, or whether they are a modern artefact.

I’m not saying here, as I often do, that things used to be better. Members of vestigial groups experience higher and more constant exposure to a wider range of infectious agents than we do, leading to a faster accumulation of memory T cells, a quicker exhaustion of the naive T cell pool and premature immunosenescence compared to industrialized populations (30).

What would happen, however, if we introduced 1-3, 1-6 beta glucans back into a world with adequate sanitation and healthcare, and an anti-inflammatory lifestyle? I believe that such an approach would delay immunosenescence, and tested this on an elderly gentleman (myself) in the dark days of first wave Covid. I shrugged the Wuhan virus off within days.

This proves nothing, of course, so let me continue on a slightly more sustainable note. Some new evidence suggests that immunosenescence may be at least partially reversible in humans, as in the rats. Pre- and probiotics look to be the tools of choice (30), accompanied by omega 3’s and polyphenols (21-23).

Finally, I return to the immunosenescence  infection / inflammation  immunosenescence doom loop.

Even among those taking prophylactic beta glucans, breakthrough chronic infections in the mouth (periodontal disease), in the gut (dysbiosis) or on a prosthetic heart valve or hip, which keep the immune system constantly activated, will accelerate the aging of the immune system (18, 32, 33). This in turn will make such infections occur more readily in the elderly, which of course reflects clinical reality; and make them more prone to spiralling down to delayed, post-infection death.

Prebiotic fibers (34) and algal-derived anti-adhesins (35) should greatly reduce these last problems. And finally, there is metformin.

This old anti-diabetic medication is regarded by many as a gerosuppressant (36), and multi-centre prospective clinical trials are planned to test this idea (37). Metformin reverses senescence in various cell types, primarily by up-regulating the energy-sensing enzyme AMP-kinase and enhancing mitochondrial function (38, 39). It has also been shown to reverse multiple aspects of immunosenescence (40-42).

If these effects are indeed mediated via AMP-Kinase then the supplement ActivAMP (a standardized extract of Gynostemma pentaphyllum aka Southern ginseng), will have a similar effect (43). Other ginsengs may also be effective (44).

The 2025 UK CMO report (1) set out the problems of infection and immunosenescense, and spelled out one answer. This was of course more vaccines and more antibiotics, as hinted at in the illustration.

An alternative, in public health terms, is health warnings on ultra-processed foods (45-48) and a switch to an anti-inflammatory diet, with the better weight management that would follow. Throw in smoking cessation and add beta glucans, prebiotics, anti-adhesins and a pinch of ActivAMP or ginseng to the next-generation functional foods, and you have a program which will keep most older people healthier for longer.

It would be safer, cheaper, more effective – and it would taste better.

ENDS

References:

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