FunkOdyssey
Seeker of Wisdom
We have the studies showing that lower thyroid function is associated with greater longevity, but you are understandably skeptical, because disease states that produce higher thyroid hormone levels may cause damage independently from thyroid hormone itself.
It may be useful then to consider experimental models in animals to demonstrate the effects of higher levels of thyroid hormones in otherwise healthy animals. From the attached paper:
THs are known to accelerate basal metabolism and increase oxygen consumption, thus leading to increased reactive oxygen species (ROS) production and oxidative stress 22,23. Additionally, THs are able to unsaturate membrane phospholipids, leading to membrane damage and mitochondria lipid peroxidation 24,25. Such pro-oxidant effects are tissue-dependent, with liver and heart more subject to oxidative stress than spleen and glycolytic muscle fibers 26. However, THs can also affect the cell antioxidant status, directly (iodine compounds act as free radical scavengers able to reduce oxidative damage in vitro) 27,28 or indirectly, by stimulating or inhibiting the activity of antioxidant enzymes 29,30 and free radical scavengers 31. Such an ambivalence in producing and counteracting oxidative stress has lead to controversial results about pro-oxidant or anti-oxidant activity by THs 31-38.
Recently, it has been demonstrated that binding of triiodothyronine (T3) to thyroid hormone receptor B (THRB) induces DNA damage and cell senescence. The mechanism of such a THRB mediated disruption of cell homeostasis is related to the activation of ataxia telangiectasia mutated (ATM)/adenosine monophosphate–activated protein kinase (PRKAA) signal transduction and nuclear respiratory factor 1 (NRF1), with consequent stimulation of mitochondrial respiration, increased production of ROS, and DNA damage ultimately leading to premature cell senescence 39. Studies in animal models seem to confirm this view. Indeed, several mice models of longevity, either naturally long-living or manipulated and genetic mutant strains, share some commons traits, among which low levels of THs. The naked mole rat (NMR), the longest-living rodent, shows very low levels of thyroxine (0.004 ± 0.001 mg/dl) 40. Moreover, it has been also shown that experimental hypothyroidism increased the lifespan of Wistar rats up to 28 months, while experimental hyperthyroidism reduced lifespan 41. Hypothyroidism was found associated with reduced ROS generation and oxidative damage, while hyperthyroidism was found associated with an increase in ROS production and a compensatory increase in anti-oxidant defense enzyme levels in several studies on murine models 29,42-44.
Ames and Snell dwarf mice represent an interesting model to investigate the impact of endocrine disorders on lifespan. They are naturally mutant mice characterized by pituitary hormone deficiencies (growth hormone -GH-, prolactin and TSH, and a consequent low level of circulating THs) resulting in small body size and delayed puberty. Ames and Snell dwarf mutant mice were found to live 40-70% longer than mice with normal thyroid hormone levels 45. It is worth noting that these mice not only live longer, but are also an example of successful aging, since they exhibit a less frequent development of age-related chronic diseases, including cataracts, kidney disease, and cancer with respect to wild type mice 45-48. Finally, long lasting administration of thyroxine was found to shorten dramatically their lifespan, though they still lived longer than wild type mice 45. In conclusion, the above described experimental studies clearly suggest that hypothyroid state may favor longevity by reducing metabolism rate, oxidative stress and cell senescence.
There's a mechanism for harm laid out by the experimental studies: running the metabolism too hot with excessive thyroid hormone increases oxidative stress, leads to premature cell senescence, and premature aging. While humans are not naked mole rats, wistar rats, or ames and snell dwarf mice, we see the same pattern in humans, where lower thyroid function is associated with longer lives. The picture that emerges here suggests a cavalier attitude toward thyroid optimization may cause harm to patients in the long run.
Many of these guy are very innovative.
