Is longevity a product of becoming more or less within a given environment?

At present, it appears that public knowledge of human physiology is at an all-time low and any sound bites of biology, seem to be served up from pharmaceutical companies. Their PR departments claim gushing success rather than wait for the previously revered, peer review process. Success not based on conclusive end points, longitudinal safety or minimal adverse events. Releases that contain words like might, may and could ,seem to be perfectly normal when elucidating success but not enveloping the concept of adverse events.  Subsequently picked up by governments that like to bask in the inconclusive success stories that require no public recourse against injury or death, and promote corrupt practice and well-rounded scientific discourse (Abbasi, 2020).

If a second-hand car salesman had a well-documented history of falsifying documents, selling unsafe vehicles, bribing licensing  departments and wrongful death. You might expect them to either be in jail or suffer  termination of their trade license at the very least?   You definitely wouldn’t want to buy a used car from said dodgy car dealer, would you? Yet here we are with large swathes of the population convinced that taking a vaccine from pharmaceutical companies with rap sheets as long as your arm and fines that could run into hundreds of billions of dollars collectively, is a good thing (Lenzer, 2011; Wise, 2001 ) (Evans, 2010)(Roehr, 2012). This isn’t hyperbole it’s documented fact.

Connecting  the relevance between ideas of how the immune system is now supposed to come from a vial and is fragile unless inoculated in such a manner. And ignoring the concepts that mRNA is not always broken down rapidly and could, just like altered metabolism create protein disturbances that impact the reverse transcriptome, altering DNA (Noble, 2012) (Noble, 2020) . Corona viruses have been with us and will be with us for a long time given that they are RNA and prone to mutation.

Industrial pollution hasn’t been around as long as viruses and bacteria but it has had the opportunity to wreak biological havoc across most life forms. So let’s turn our attention to the concept of longevity and that most deaths globally still come from heart disease, cancer, starvation and other metabolic diseases.  My own belief is that if we were as advanced a civilisation as we contend, then surely this could be measured by an ageing population’s robustness, not its fragility?

Maintaining longevity is contentious, some people believe less thyroid function promotes longevity, whilst others (including myself) think the opposite. An increasing trend is that the factors that prevent life from occurring probably contribute to a decrease in longevity, and these can include compounds and agents found in air, water, food and medicines (Dong et al., 2021)(Balasubramanian et al., 2013)(Colborn, Vom Saal, & Soto, 1993).

With the above quote in mind, you might have a better idea why some people with failing biology like to emigrate to hotter countries where their body temperature can be maintained without consideration of why?  The absence of long days of winter replaced with an abundance of UV, red and orange spectrums of light that also promote health and to a degree also explain viral susceptibility (Walrand, 2021).

 Anecdotally and in a number of papers the suggestion is that decreased thyroid function, lowered metabolic rate and higher TSH values is associated with longevity. That might be useful to consider if that’s what all of the data suggests but it doesn’t, and even the concept of increased pituitary responses like TSH is problematic. Many studies in both knock out (KO) mice and animals with hypophysectomy have shown that reduced pituitary hormones are associated with longevity (in rodents and dogs at least) (Brown-Borg, 2015). Growth hormone in particular is associated with cancer, diabetes and increased mortality. Fasting has a double whammy effect of increasing growth hormone and suppressing thyroid hormone production. I wrote previously on why fasting makes individuals colder and in some cases less flexible. Fasting can be a useful tool if you over eat but all of the processes like autophagy, biogenesis and detoxification all occur optimally with adequate nutrition.

I can hear all the biohackers spitting out their resveratrol and metformin in disgust as I write. Short term fasting (previous blog on fasting and decreased metabolism) or CR temporarily increases TSH that is suppressed as chronic glucocorticoid and adrenaline production suppresses TSH. Sustained TSH production is associated with fibrosis, interleukin 6, hyperplasia of thyroid follicles and thyroid cancer (Antunes, Gagnon, Langille, & Sorisky, 2008). There are many reasons why maintaining a low TSH value is healthy and to be strived for. The pituitary gland after all,  receives signaling (via feedback loops -proteins/serum/hypothalamus/neurotransmitters) that autonomous conversation of hormones is lowered and, in some cases, associated organs are failing. Loss of gonadal hormones causes both LH and FSH, lack of adrenals ACTH and low thyroid requires TSH. The more chronic the output the increased likelihood of disease progression.

Far too many clinicians  still view the thyroid stimulating hormone (TSH) assay (blood test) as the gold standard despite a vast mounting body of evidence that pollution alters not just thyroid hormone conversion but more importantly act as thyroid hormone receptor agonists, alter binding, feedback loops and in utero can reset the TSH set point, potentially invalidating any blood test.

This probably explains the reductionism of prescription and why vast amounts of single action medications are handed out for cholesterol, blood sugar and hypertensive patients. Even studies that have claimed not to show success with the use of T4 monotherapy have failed to entertain a subject’s nutritional status or failed to consider that pollution and other stressors may not promote optimal conversion of T4 to T3.

Thyroid hormone values and longevity have provided conflicting results but optimal values of both T4 and T3 appear to correlate with more robust and increased functional capacity in centenarians (Arosio et al., 2020).

 Many of the TSH values reported with adequate T4/T3 values appear to have TSH values between 2-4 m/ULs, and these increases could be reflective of the increased stress and loss of both thyroid hormone conversion and function. After all, the very nature of pituitary TSH production is to support the peripheral loss of T4 to T3 conversion. Perhaps instead of the association of increasing TSH value recorded in centenarians being perceived as healthy, it could be perceived as the gradual loss of function, that might be offset with adequate thyroid hormone. After all thyroid contributes to complexity not just the oxidative metabolism needed to maintain complexity.

Far from equilibrium thermodynamic reactions are at the heart of complexity and needed for maintaining long range order and the structures and function that can contribute to increased complexity. Loss of complexity, particularly aerobic metabolism will of course decrease longevity.

 What’s known is that mammals regulate the body temperature in a tight window of 37C (98.6F) and when that’s lost, a relative reduction of function occurs through alteration of key enzymes, up regulation of stress hormone pathways and reductive metabolism when chronic..

In the study of centenarians and their off spring (Jansen et al., 2015) you can observe that thermogenesis is maintained at 37 degrees centigrade (C) and the lowering of body temperature occurs at night when TSH is at its highest and correlates with the known increases of cortisol, growth hormone and melatonin associated with sleep.

So when is too much TSH really too much?

I have no problem with the values reported here as they are ranging from 2.5 – 4 mU/L at an advanced age. It’s still considered within a normal reference range( some suggest with subclinical thyroid issues TSH up to 10 mU/L is acceptable) but given what we know about chronic pituitary responses and disease, it might be prudent to further minimise the pituitary response by maintaining adequate T3 values. Much like the split in opinion of treating subclinical hypothyroidism with synthetic T4 (Ochs et al., 2008) (Surks, Goswami, & Daniels, 2005), there’s often not enough clarification of  a study group’s need for adequate nutrition, T3 over T4 or blocking factors like adequate selenium, zinc or vitamin A that promote optimal thyroid hormone conversion.

An optimal window of 36.5 C or so on waking, progressing to 37 C in a fed and most likely light exposed body, might just be one of the most useful markers for both metabolic function and longevity. The relationships between thyroid, old age, colder and slower bodies is an insight to human potential. Integrating a more nuanced approach to thyroid which incorporates optimal food choices, light exposure, adaptive substances, and probably most importantly minimal iatrogenesis could be a nudge in the right direction?

Much like temperature and basal metabolic rate was frowned upon by doctors who accepted the analysis of complex thyroid physiology with a binary lock and key test in the form of TSH analysis. The  cultivation of social  divides and medical interventions to undermine an individual’s capacity to assess and manage their own health is always the goal to generate more income for companies that don’t like to think about ordered consequences and transgenerational effects. Looking after yourself and understanding how to do it has never been so pertinent.

 

References:

Abbasi, K. (2020). Covid-19: Politicisation, “corruption,” and suppression of science. The BMJ. https://doi.org/10.1136/bmj.m4425

Antunes, T. T., Gagnon, A., Langille, M. L., & Sorisky, A. (2008). Thyroid-stimulating hormone induces interleukin-6 release from human adipocytes through activation of the nuclear factor-κB pathway. Endocrinology. https://doi.org/10.1210/en.2007-1588

Arosio, B., Monti, D., Mari, D., Passarino, G., Ostan, R., Ferri, E., … Vitale, G. (2020). Thyroid hormones and frailty in persons experiencing extreme longevity. Experimental Gerontology. https://doi.org/10.1016/j.exger.2020.111000

Balasubramanian, P., Sirivelu, M. P., Weiss, K. A., Wagner, J. G., Harkema, J. R., Morishita, M., … MohanKumar, S. M. J. (2013). Differential effects of inhalation exposure to PM2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats. NeuroToxicology, 36. https://doi.org/10.1016/j.neuro.2012.02.016

Brown-Borg, H. M. (2015). The somatotropic axis and longevity in mice. American Journal of Physiology - Endocrinology and Metabolism. https://doi.org/10.1152/ajpendo.00262.2015

Colborn, T., Vom Saal, F. S., & Soto, A. M. (1993). Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives. https://doi.org/10.1289/ehp.93101378

Dong, X., Wu, W., Yao, S., Li, H., Li, Z., Zhang, L., … Zhang, F. (2021). PM2.5 disrupts thyroid hormone homeostasis through activation of the hypothalamic-pituitary-thyroid (HPT) axis and induction of hepatic transthyretin in female rats 2.5. Ecotoxicology and Environmental Safety, 208. https://doi.org/10.1016/j.ecoenv.2020.111720

Evans, R. G. (2010). Tough on crime? Pfizer and the CIHR. Healthcare Policy. https://doi.org/10.12927/hcpol.2010.21778

Illich, I. (2003). Medical nemesis. 1974. Journal of epidemiology and community health (Vol. 57). https://doi.org/10.1136/jech.57.12.919 (short review by Illich of full text)

Jansen, S. W., Akintola, A. A., Roelfsema, F., Van Der Spoel, E., Cobbaert, C. M., Ballieux, B. E., … Van Heemst, D. (2015). Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism. Scientific Reports, 5. https://doi.org/10.1038/srep11525

Lenzer, J. (2011). Pfizer settles with victims of Nigerian drug trial. BMJ (Clinical Research Ed.). https://doi.org/10.1136/bmj.d5268

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Ochs, N., Auer, R., Bauer, D. C., Nanchen, D., Gussekloo, J., Cornuz, J., & Rodondi, N. (2008). Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med, 148(11), 832–845. https://doi.org/0000605-200806030-00225 [pii]

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Surks, M. I., Goswami, G., & Daniels, G. H. (2005). The thyrotropin reference range should remain unchanged. Journal of Clinical Endocrinology and Metabolism, 90(9), 5489–5496. https://doi.org/10.1210/jc.2005-0170

Walrand, S. (2021). Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-81419-w

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