Let me Count the Ways

We are all products of our environment. Being mildly Jewish, raised in a Presbyterian culture and the eldest of 4 children, I am ridiculously obsessed with taking care of others and racked with guilt when, for whatever reason, I fail to carry out what I believe to be my duties.

If I had known then what I know now, I am certain I could have offered my beloved parents a little more life. I miss their wisdom. Every day I regret that my brother accepted the widely promoted fear porn of the Covid mRNA shots. I miss his obduracy. Had I been a better father, I would have seen more of my children’s beautiful growing.

But wait – there’s more.

I am offended, hugely, by the ongoing massacre of the relatively innocent, evidenced by multiple rising tides of non-communicable disease (1). Such a vast and continuous waste of potential and life, epitomised for me by the attractive (if misguided) Ophelia thinking blue thoughts in a green shade while drowning in a river of tears and cheap salad dressing.

Apologies for that needle scratch. I find some pre-Raphaelite art quite beautiful, but the claimed high moral seriousness often seems maudlin to me. Then again I am a scientist, of sorts.

In my Presbyterian and post-Raphaelite world, salad dressing is made with olive oil, vinegar and mustard. Everything else is optional. Conagra, Hormel, Kraft Heinz, Unilever and their multinational kin, however, take a different view. The salad dressings they pour into the global trough are full of seed oils and therefore omega 6 fatty acids, which in excess turn healthy foods into unhealthy ones.

Their ultra-processed products are defective in many other ways too, being not only pro-inflammatory but also calculated to cause dysbiosis, glycaemic overload and type B malnutrition. They are calorie-dense and nutrient-lite, with the exception of sodium which they cram into us as if there were no tomorrow. And for too many of us there isn’t, because new evidence shows that these foods accelerate our travel through time.

A recent publication (2) found that ultra-processed foods (UPFs) speed up biological ageing, as measured by a range of 36 age-sensitive blood biomarkers. Conversely, a more natural diet was associated with slower ageing. This research was generated by a group of Italian scientists with huge expertise in the relationship between diet and health, and whose work I respect.

It simultaneously consolidated and discredited prior work by a team primarily from the august Stamford University School of Medicine (3), which had found time-related negative changes in oxidative, inflammatory and other metabolic sequences linked to the degenerative clinical changes routinely observed in ageing populations.

According to Stamford, humans undergo two major downgrades in molecular markers for ageing and in microbiotas at the ages of 44 and 60. This indicated, the researchers said, that ageing was a non-linear process, and explained why the frequency of degenerative conditions increases non-linearly with age.

But did their findings really reveal inevitable epigenetic and metabolomic truths? Or did they merely reflect an all-American corn-fed bias?

The researchers performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants aged between 25 years and 75 years. 108 is a worryingly small number, but there are at least two more substantial problems. Firstly, the authors did not follow any one individual for very long. Trial subjects were tracked for a median period of only 1.7 years, so the claimed non-linearity is derived from different groups of individuals. Secondly, and more seriously, all the participants resided in California.

Americans consume more ultra-processed food (UPF) than almost anyone else, hitting an average 60% of calorie intake (4). Higher consumption of UPFs is linked to increased oxidative stress, dysbiosis and immune dysregulation (5, 6) together with an increased risk of many degenerative conditions (7-12), and early death (13), in a dose-related manner (14).

Given the prevalence of UPF’s and the long latent phases of most degenerative conditions, it is unsurprising that most non-elderly 21^st century humans now show pre-clinical signs of many of the chronic non-communicable diseases (ie 15-19).

It is likely, therefore, that the Stamford scientists found nothing more than the multi-omic echoes of a poisoned population and then extrapolated, from sick and intoxicated individuals, something they mistakenly believed to be a general truth. In reality the trial subjects were victims of the American industrial diet, and the scientists victims of sampling error.

They had overlooked the sickly local diet and missed some particularly glaring clues. In the USA, poor eating habits and lack of exercise (20) ensure that cardiovascular health scores begin to decline (ie show biological ageing) at the abnormally young age of 10 (21); that roughly 90% of all Americans are metabolically skewed and unfit (22, 23), and that a similar percentage have one or more nutrition-related chronic diseases (24).

These astonishing examples of accelerated and almost universal pathology indicate that the ‘non-linear changes’ reported by the Stanford team are not intrinsic to the ageing process at all. They are what one inevitably finds in modern, intoxicated and fundamentally unhealthy trial subjects, who are not consuming, for example, even threshold levels of prebiotic fibers (25).

The modern population is chronically malnourished and chronically poisoned. It therefore experiences a combination of chronic inflammatory stress, dysbiotic stress, oxidative stress, oxidative phosphorylative stress, glycative stress, carbonylative stress and carbamylative stress, together with type B malnutrition (ie 26-32).

These multiple stressors account for a good deal of the phenomenology of ageing as we experience it, but that does not mean that this phenomenology is inevitable. In fact, it is strong evidence that a good deal of the age-related pathology that floods our healthcare systems is an artifact, because each of those stressors can be countered. The Italian data (2) strongly support this idea, and there are at least three additional lines of supporting evidence.

Firstly, and as cited in previous posts, the loss of kidney function (cited in the Stamford paper), the loss of hippocampal structure and neurogenesis, the rise in blood pressure and the growth of the prostate (none of these are cited) do NOT occur in vestigial groups (33-41) whose UPF-free diet and lifestyle reduce many of the above stressors.

Secondly, better food slows progress to death, a process most easily seen in hospital patients (ie challenged individuals) in whom better nutrition significantly reduces mortality (42).

Thirdly, there is a growing body of evidence that replacing those key nutrients which are depleted in the industrial diet, and which are known to reduce many of the stressors listed above, can slow, stabilize and even reverse some of the deepest aspects of the ageing process (ie 43-46).

For example …

One key element within the ageing process is the progressive down-regulation of various aspects of cellular energy production, creating an increased risk of many degenerative diseases (47, 48) and an increased tendency to accumulate adipose tissue (49). A new paper shows that the omega 3 PUFAs can remedy this process.

These fatty acids are the endogenous agonists of peroxisome proliferator-activated receptor α (PPARα), which stimulates lipid oxidation and catabolism. They had already been shown to enhance ADP sensitivity in human muscle tissue (50), so it is not surprising to find that in aged animal models the Omega-3 PUFAs boost fatty acid beta oxidation and ATP synthesis in multiple organs (51), thereby reversing a deep component and driver of biological ageing.

Another deep element within the ageing process is the gradual shortening of telomeres, and there is persuasive evidence that the omega 3 fatty acids can attenuate this also (52).

There is a plausible rationale for co-supplementing with fatty acid amides. Palmitoylethanolamide and oleoylethanolamide are also endogenous PPARα agonists (53, 54), albeit with subtly different applications (55).

Consider, too, the polyphenols, which provide a complementary range of anti-ageing effects (ie 56-59). The prebiotic fibers add a different set again (60), presumably via microbiotal modulation and the repairing of colonic epithelial barrier function (61). The 1-3, 1-6 beta glucans provide a fourth set of anti-ageing effects via restoration and normalisation of innate immune function (ie 62-66).

All the usual suspects are listed here, and the answer concealed in the title is therefore four. Or five. Or more.

EndNote. I am taking time off from the blog to collaborate on a medeconomic paper. This post will be the last for a while, so I re-visited a few previous themes and tried to re-string an old narrative. Dear readers, thank you for your indulgence – and for the next few months, I hope you won’t mind if the posts are rather more irregular than usual.

Next post:

I am currently fascinated by Sonofabitch stew, and other pharmacologically active regional dishes that can be loved only by those raised on them. I intend to explore a smorgasbord of rakfisk, stinking tofu, garum, broiled tendon, seagull wine, blood sausage and pig brains, together with their medicinal effects, at my earliest convenience.

References:

1. Diseases trending upwards include Addiction, Adenomyosis (probably), Allergy, Alopecia, Anxiety, Asthma, Atrial fibrillation, Autoimmune diseases, Borderline Personality disorder, BPH, Cancer esp in younger people (bone marrow, brain, breast, colorectal, endometrium, esophagus,  gall bladder/duct, gastric, head and neck, kidney, liver, pancreas, prostate, thyroid), Cataracts, Chronic illness in children, Chronic pain, Chronic pain in children, Conduct Disorder, Dementia, Depression, Dermatoporosis (probably), Diabetes 1 and 2, Eating disorders, Endometriosis, Epilepsy, End-stage renal disease, Eosinophilic gastrointestinal disease, Fibroids, Frailty syndrome (falls, immobility, delirium, incontinence, iatrogenic illness), Gender Dysphoria, Glaucoma Gout, Hikikomori, Hypertension, Infectious diseases (some), Irritable Bowel Syndrome, Inflammatory Bowel disease, Infertility, Intermittent Explosive disorder, Ischaemic Stroke, Lipidema, Metabolic Dysfunction-Associated fatty liver disease & steatohepatitis, Myopia, Obesity, Oppositional Defiant Disorder, Osteopenia, Osteoporosis, Parkinsonism, Sarcopenia, Sepsis (probably), Spectrum disorders (ADD, ADHD, Asperger’s, Autism, Dysphasia, Dyspraxia, Schizophrenia), Stunting, Thrombosis, Trauma-induced brain damage. This is not a complete list. Use the disease name and the word ‘trend’ in your search engine to find references, all of which can be found in recent presentations I have given to medical audiences in many countries.    
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