27 replies to this topic

[Michael]

All:

The Ames and Snell long-lived dwarf mice get that way because a pituitary defect which leads to low GH and IGF1; it also, however, leads to very low TSH, with the result that they have low thyroid hormones and thus low thyroid hormone signaling. CR rodents and human and nonhuman primates have a different but FUNCTIONALLY similar pattern: high TSH but normal (or low-normal) T4, combined with quite low bioactive T3, is what is observed in CR, suggesting a regulated 'altered setpoint' in the CR state that still reduces bioactive T3.

About this time last year, Barzilai's group reported that "Extreme Longevity is Associated with Increased Serum Thyrotropin" in long-lived families of Ashkenazi Jews.(1) Specifically, they had high TSH, but NORMAL T4, with an inverse CORRELATION between the 2 hormones, suggesting a state of "resistance" to TSH and possibly a kind of functional hypothyroidism; unfortunately, they didn't measure T3 (let alone free T3 or rT3) to get a more comprehensive picture. As the authors state,

The TSH population shifts to higher concentrations with age appear to be a continuum that extends even to people with exceptional longevity. The inverse correlation between TSH and FT4 in our populations suggests that changes in negative feedback may contribute to exceptional longevity.(1)

This of course sounds similar to the CR findings.

A new study (4) has now reported functionally similar (and if anything, even more suggestive) findings in the Leiden Longevity Study. This is a cohort study of the middle-aged offspring of parents who are both nonagenarians, and have nonagenarian siblings, which uses their middle-aged partners as the reference group (since their diets and lifestyles will be pretty closely matched). They found that:

When compared with their partners, the group of offspring of nonagenarian siblings showed a trend toward higher serum thyrotropin [TSH] levels (1.65 vs 157 mU/L, p = .11) in conjunction with lower free thyroxine [T4] levels (15.0 vs 15.2 pmol/L, p = .045) and lower free triiodothyronine [T3] levels (4.08 vs 4.14 pmol/L, p = .024). Conclusions: Compared with their partners, the group of offspring of nonagenarian siblings show a lower thyroidal sensitivity to thyrotropin. These findings suggest that the favorable role of low thyroid hormone metabolism on health and longevity in model organism is applicable to humans as well.(4)

And, although weaker because in younger-old people or because of weaker associations, several previous studies had also come to similar conclusions. (2) reported that in the general population of individuals aged 85-89, "Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status". (3) found that they could predict "all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result [in] a 10-year cohort study" of people 60 and over.

Again, this points to the low bioactive thyroid status induced in humans on CR being linked to the potential for extreme longevity in our species, providing another lightly-penciled "check" on the list of likely signs that CR will retard aging in humans.

References
1. Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I. Extreme Longevity is Associated with Increased Serum Thyrotropin.
J Clin Endocrinol Metab. 2009 Apr;94(4):1251-4. Epub 2009 Jan 21. PMID: 19158193

2. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG.
Thyroid status, disability and cognitive function, and survival in old age. JAMA.
2004 Dec 1;292(21):2591-9. PubMed PMID: 15572717.
http://jama.ama-assn...ull/292/21/2591

3. Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001 Sep 15;358(9285):861-5.
PubMed PMID: 11567699.

4. Rozing MP, Westendorp RG, de Craen AJ, Frölich M, Heijmans BT, Beekman M, Wijsman C, Mooijaart SP, Blauw GJ, Slagboom PE, van Heemst D; on behalf of the Leiden Longevity Study (LLS) Group. Low Serum Free Triiodothyronine Levels Mark Familial Longevity: The Leiden Longevity Study. J Gerontol A Biol Sci Med Sci. 2009 Dec 16. [Epub ahead of print] PubMed PMID: 20018826.

[athrahasis]

Michael,

I've recently read that 'chubby people' live longer. Is it another datapoint? Given that depressed thyroid functionality can in fact make one chubby.

[niner]

I've recently read that 'chubby people' live longer. Is it another datapoint? Given that depressed thyroid functionality can in fact make one chubby.

I don't think so. This just tells us that really skinny people are at a health disadvantage. (BMI < 18.5, or so.)

[tunt01]

i seem to recall reading that resveratrol doesn't produce this sort of thyroid hormone profile we see in practitioners of CR. is that the consensus?

[JLL]

Michael,

I've been trying to find the thread where you argue against the idea that humans on CR should try to lower their IGF-1 levels too (by cutting back on protein), but I can't. Can you briefly summarize your point again here? Cheers.

[Michael]

i seem to recall reading that resveratrol doesn't produce this sort of thyroid hormone profile we see in practitioners of CR. is that the consensus?

I don't think there IS a consensus, or even reliable data; what has been reported doesn't sound healthy in normal, healthy rodents, but we doin't have enough detail on the report.

One group found that "5 microg and 50 microg RES/kg bodyweight per day given to ovariectomized (OVX) rats ... revealed no estrogenic potential on pituitary function in vivo " (1) but that the same dose in the same model "lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHß mRNA in the adenohypohysis and E2 treatment attenuates this effect. ... In all animals, we could not detect changes in thyroid morphology" (2).

OTOH, heretofore-unpublished work performed in Saudi Arabia (which is not a center of rigorous oversight of scientific protocol) reports that RES, at higher doses, lowers (ie, tends to normalize) thyroid fundction in hyperthyroid rats, but by lowering the original stimulus (unlike in CR), and "has goitrogenic effect in normal rats":

3 doses of trans-resveratrol (200, 400, and 800µg/kg/day) orally for 4 weeks significantly increased thyroid weight and relative thyroid weight. Trans-resveratrol (200µg/kg/day p.o.) for 4 weeks significantly increased serum TSH level and decreased both serum T4 and T3 levels ... significantly inhibited microsomal TPO activity ... [and] inhibited thyroid SOD activity ... . The 3 doses of trans-resveratrol significantly stimulated thyroid GPx activity. ... Different doses of trans-resveratrol in bleomycin-induced DNA damage in vitro test, had no pro-oxidant effect. Trans-resveratrol (200µg/kg/day p.o.) for 4 weeks has goitrogenic effect in normal rats ... [which] may be due to competitive inhibition of TPO activity due to structural resemblance of TPO substrate (tyrosine residues) in thyroglobulin or due to decrease H2O2 (TPO cofactor) level in thyroglobulin due to inhibition of thyroid SOD activity and stimulation of GPx activity. ... Also, the goitrogenic dose of trans-resveratrol had curative effect in hyperthyroid rats in comparable manner with the effect of PTU as classic antithyroid drug.(3)

Functionally, remember that "Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction" (4) as one would expect from functional hypothyroidism; and, as summarized previously,

In mice, resveratrol doesn't fully replicate CR-induced gene expression changes (ref) nor induce some demonstrably important CR-induced metabolic changes (ref). Heck, it's not even clear that the stuff does any good in yeast (where the whole hype got started) (ref); nor in Drosophila elegans (note that Partridge's group is possibly the most experienced lab in the world in doing lifespan studies in Drosophila) (ref); nor in another (tephritid) species of fruit flies ((ref): there may have been a marginal effect in flies fed 1 of the 24 different diet combinations, but I'm skeptical of that result, and IAC there was no effect in the other 23 diets); nor in C. elegans (ref)

But really, even this is sliding too far into the weeds. Resveratrol does not ultimately deliver the anti-aging effects of CR(5):

Figure 1: Effects of resveratrol on mice fed Standard Diet (SD), Every-Other-Day (EOD) feeding (leading to ~10-15% CR), or fed a high-calorie diet (HC) ad libitum at a Low (100 mg/kg of food, SDLR, EODLR, or HCLR), or high (400 mg/kg of food, SDR, EODR, or HCR). "Later, additional groups of mice were given a higher dose of resveratrol along with the standard or HC diets (2400 mg/kg of food, SDHR, or HCHR)." From (5)

-- so ultimately, who cares what it may or may not do to some particular CR-associated metabolic parameter?

I've recently read that 'chubby people' live longer. Is it another datapoint? Given that depressed thyroid functionality can in fact make one chubby.

... but the number of such people is extremely rare, despite the corrosive effects of Broda Barnes and later "natural hormone replacement" enthusiasts ...

I don't think so. This just tells us that really skinny people are at a health disadvantage. (BMI < 18.5, or so.

It doesn't really even show that, but that's a topic for another day ...

I've been trying to find the thread where you argue against the idea that humans on CR should try to lower their IGF-1 levels too (by cutting back on protein), but I can't. Can you briefly summarize your point again here? Cheers.

See here, and here -- and do be sure to follow the embedded links.

That said, however, my understanding of the value and place of protein in a human CR diet is now much more nuanced: despite prima facie reading of the rodent evidence on protein and lifespan op cit and the human data on level of IGF1 vs health outcomes, the evidence of low IGF-1 signaling and activity in human exceptional longevity and other data are beginning to shift my views. I am no longer convinced that the valuable benefits of relatively high protein intake in the AL population extend to people on CR. Please keep the latter especially in mind when reading it.

I realize that this last paragraph sounds earth-shattering to some; I apologize if it takes me quite some time until I have time to fully explain and document the nuances and basis of my new, revised view, which is certainly not just "protein bad."

References
1: Böttner M, Christoffel J, Jarry H, Wuttke W. Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats. J Endocrinol. 2006 Apr;189(1):77-88. PubMed PMID: 16614383.

2. Böttner M, Christoffel J, Rimoldi G, Wuttke W. Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on the pituitary-thyroid-axis. Exp Clin Endocrinol Diabetes. 2006 Feb;114(2):82-90.
PubMed PMID: 16570238.

3. Ibrahim Abduh Khardali. Effects of resveratrol on thyroid function in normal and hyperthyroid Rats: a mechanistic study. Submitted In Partial Fullfilment Of The Requirements For The Master's Degree In Toxicology Department Of Pharmacology College Of Pharmacy King Saud University. 1428 H- 2007 G

4. Mayers JR, Iliff BW, Swoap SJ. Resveratrol treatment in mice does not elicit
the bradycardia and hypothermia associated with calorie restriction. FASEB J.
2009 Apr;23(4):1032-40. Epub 2008 Dec 4. PubMed PMID: 19056839; PubMed Central
PMCID: PMC2660640.

5. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R.
Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span.
Cell Metab. 2008 Aug;8(2):157-68.
PMID: 18599363 [PubMed - as supplied by publisher]

Edited by Michael, 21 February 2010 - 10:32 PM.
Better images & captioning for graphs

[Luna]

I read the title and thought "Oh no, I have high or above average TSH all the time in my tests". So actually, high TSH *BUT* low T3 and T4 is a the good thing?

[Michael]

All:

First, some additional background on thyroid hormone and the anti-aging effects of CR (including in particular evidence of the low bioactive T3 playing a role in life extension in other paradigms) here; more on its effects on the biochemical profile of human CR folk here (skip down to the discussioin of macrocytic anemia). See also this textbook chapter on "Effects of the Environment, Chemicals and Drugs on Thyroid Function," beginning with the section headed "Nutrition."
 

I read the title and thought "Oh no, I have high or above average TSH all the time in my tests". So actually, high TSH *BUT* low T3 and T4 is a the good thing?

Well, 2 things ... First, the prototypal CR pattern is (high) normal TSH, NORMAL T4, and low T3 (especially free T3 -- as well as high rT3, which is only rarely performed): again, the body is responding properly to TSH by producing T4, but is activelyconserving energy by not making it bioactive. So, not quite. Second, did this profile only emerge AFTER you took up CR? If it's from other causes, it COULD be actually pathological, or you could just be lucky.

Have your docs ever given you an explanation for WHY you have this pattern, or just said 'hypothyroid' and been done with it? (I'm curious, but can't help you much to answer the origins question if it's NOT pathological nor linked to CR).

Edited by Michael, 22 July 2017 - 09:46 PM.
Updating dead link

[Luna]

I think it was before CR. I am not sure if I am really on CR at the moment is my BMI is probably about 22.7 according to some online calculator.
They never said I have hypothyroidism either, they pretty much ignored the fact that my TSH was higher than the lab indicators probably because T3 and T4 were about normal.

I just looked at my old blood tests. TSH used to be a bit over 6.0, a bit more than 2.0 over the range they have here (0.39-4.0). T4-FREE was exactly in the middle of the range. T3-FREE wasn't tested.

In the latest test they only had TSH which is only about 3.16, so higher average but not really "high". :( (?)

They were always more worried about my high prolactin tests (which sometimes was about double than the maximum.. and no I am not pregnant :D) but never cared to do anything about that either, I guess because it never kept increasing.

Edited by Luna, 06 March 2010 - 09:10 AM.

[Sillewater]

Would a protein-restricted diet produce the same thyroid hormonal profile?

From the book MR posted:

Protein-Calorie Malnutrition (PCM)

As in the case of starvation, PCM is associated with a low serum T3 concentration and increased rT3 levels, probably due to similar changes in iodothyronine monodeiodination. However, important differences exist between the abnormalities in thyroid function observed in PCM and acute calorie deprivation. Most reports indicate important decreases in TBG and TTR concentrations, and there are also indications of hormone binding abnormalities.70,71 As a consequence, the free concentrations of both T4 and T3 are usually normal.70,72,72a Recovery is associated with restoration of the level of serum thyroid hormones and binding proteins. Despite an accelerated turnover time, the absolute amount of extrathyroidal T4 disposed each day is reduced. Refeeding restores the T4 kinetics to normal.70 The thyroidal RAIU is reduced due to a defect in the iodine-concentrating mechanism.73 The most striking difference between starvation and PCM is the finding the latter of an exaggerated and sustained TSH response to TRH, with basal TSH levels either elevated or normal.70,72,72a,72b,74

The experimental model of protein malnutrition in the rat yielded different results from those observed in humans. Serum T4 and T3 levels were found to be both elevated.75 However, in the lamb, as in humans, chronic malnutrition leads to a lower rate of T4 utilization.76

Don't quite understand what it says beyond the first sentence. To me it seems the profile might not be similiar if you calorie restricted, however what if you ad lib or intermittent fasting?

[Sillewater]

Does nicotinic acid give the right profile? (I have not yet read the text on thyroid hormones that MR posted but will soon).

Mayo Clin Proc. 1995 Jun;70(6):556-8.


Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state.
Shakir KM, Kroll S, Aprill BS, Drake AJ 3rd, Eisold JF.

Division of Endocrinology and Metabolism, National Naval Medical Center, Bethesda, Maryland 20889-5600, USA.


Abstract
OBJECTIVE: To evaluate the effects of nicotinic acid on serum thyroid hormone levels in the absence of systemic illness or hepatic dysfunction. DESIGN: We determined the effect of treatment with nicotinic acid on serum thyroid hormone levels in one female and four male patients (mean age, 44.4 years) with hyperlipidemia. MATERIAL AND METHODS: In the five study patients, we measured serum lipids in conjunction with serum thyroxine (T4), triiodothyronine (T3) resin uptake, T3, free T4, thyroid-stimulating hormone (TSH), and thyroxine-binding globulin before, during, and after treatment with nicotinic acid. RESULTS: Serum lipid levels responded appropriately to nicotinic acid treatment. Thyroid function studies done a mean of 1.3 years (range, 0.5 to 3.5) after initiation of nicotinic acid therapy (mean daily dose, 2.6 +/- 0.7 g) revealed significant decreases in serum levels of total T4 (21%), free T4 index (16%), T3 (13%), and thyroxine-binding globulin (23%) (P < 0.02), whereas no significant changes were noted in free T4, T3 resin uptake, and TSH levels. During the course of treatment, the patients, who were carefully questioned, had no symptoms of hypothyroidism. Hypothyroidism was further excluded in three patients who had a normal serum TSH response to administration of thyrotropin-releasing hormone. In two patients, measurements of thyroid function returned to pretreatment levels after discontinuation of nicotinic acid therapy. No patient had significant abnormalities in liver-associated enzymes or evidence of systemic illness during the course of treatment. CONCLUSION: These results suggest that nicotinic acid decreases serum thyroid hormone concentrations while maintaining a euthyroid state. This effect may be mediated through reduction in thyroxine-binding globulin, but other mechanisms may also be involved.

PMID: 7776715 [PubMed - indexed for MEDLINE]

[Mia K.]

I received yesterday the results of a few blood tests I had run @LabOne through healthcheckusa.com.

Thyroid:

TSH  3.51 uIU/mL  (Reference Interval 0.450 - 4.500)

Free T4   2.2 pg/mL (RI 2.0 - 4.4)

T4, Free(Direct)  0.96 ng/dL (0.82 - 1.77)

No thyroid antibodies detected.  

Thoughts?  I've no symptoms of hypothyroidism; my body temp runs low, but I assume this is due to calorie intake. (CRON-o-meter says ~1750kC day 23%P/65F/11CHO, w/at least 100% of RDA for everything but carbs, potassium, iron and calcium, ridiculously high in Se due to my penchant for Brazil nuts).  (I'm 5'10/110lbs)

I've been using Dr. Ron Rosedale's optimums as my health guidelines.  You've probably come across on-line his article on the metabolic effects of insulin.  In his book The Rosedale Diet (HarperCollins, 2004) the good Dr. writes:  The ideal blood level of free T3 is 2.2 to 3.0 pg/mL and, within this range, the lower the level, the better, provided that TSH is within the healthy range of 1.5 to 3.5.  He writes that this is where the metabolism is most efficient.  I certainly feel well! 

I did purchase some 1/4 grain (15mg) Armour tabs a year or so ago (TSH was ~3) thinking I was hypo-t,  but I don't take it.

Question: is there any relationship between TSH/thyroid  and Vitamin D levels?  My (w/supplementation) 25(OH)D is up to 82.3 ng/dL.

Thanks & Cheers,
Mia, eagerly awaiting Michael's new, revised view of dietary protein.  Especially the nuances. 

Edited by Mia K., 23 July 2010 - 06:37 PM.

[Michael]

First, a followup: yet another study finding low bioactive thyroid hormones in extreme familial longevity:

We found that a lower family mortality history score (less mortality) of the parents of nonagenarian siblings was associated with higher serum TSH levels (P = 0.005) and lower free T4 levels (P = 0.002) as well as lower free T3 levels (P = 0.034) in the nonagenarian siblings.

Conclusions: Our findings support the previous observation that low thyroid activity in humans constitutes a heritable phenotype that contributes to exceptional familial longevity observed in the Leiden Longevity Study.(1)

I received yesterday the results of a few blood tests ...

TSH  3.51 uIU/mL  (Reference Interval 0.450 - 4.500)
Free T4   2.2 pg/mL (RI 2.0 - 4.4)
T4, Free(Direct)  0.96 ng/dL (0.82 - 1.77)
No thyroid antibodies detected.  

Thoughts?  I've no symptoms of hypothyroidism; my body temp runs low, but I assume this is due to calorie intake.

Are you actively on CR? Do you have pre-CR data? CR usually leads to a pattern of low bioactive T3, but high- or high-normal TSH; your case certainly looks more like some kind of defect in secretion of TSH, but it's hard to say It's certainly reassuring that you have no antithyroid antibodies, no symptoms of hypothyroidism aside from teh low body temp, and "certainly feel well!"; however, I am not a medical doctor, let alone a endocrinologist, and even if I were of us were, I've never examined you, dn't know your medical history, etc; plus, you didn't get any T3 or rT3 testing.

I've been using Dr. Ron Rosedale's optimums as my health guidelines.

Er ... why?

eagerly awaiting Michael's new, revised view of dietary protein.  Especially the nuances. 

Far from covered the nuances, but did you see this post on my revised view on IGF-1 and protein for people on CR?

Reference
Familial Longevity Is Associated with Decreased Thyroid Function.
Rozing MP, Houwing-Duistermaat JJ, Slagboom PE, Beekman M, Frölich M, de Craen AJ, Westendorp RG, van Heemst D.
J Clin Endocrinol Metab. 2010 Aug 25. [Epub ahead of print]
PMID: 20739380

[Michael]

All:

Although weaker than other cases (small study population, cross-sectional design), here is yet ANOTHER such report:

Objectives: to verify whether declining levels of circulating thyroid hormones may contribute to longevity.

Design: cross-sectional observational study. ...

Subjects: six hundred and four home-dwelling subjects (301 females, 303 males), divided into three groups: 278 individuals 60-85 years old; 179 children or nieces/nephews of centenarians who are 60-85 years old; 147 individuals older than 85 years. ...

Results: FT3 and FT4 levels were negatively associated with age. Lower levels of FT3, FT4 and TSH were found in centenarians' children and nieces/nephews with respect to age-matched controls. Indeed, being a relative of centenarians qualified as an independent correlate of thyroid parameters.

Conclusions: age-related subtle thyroid hypofunction (either due to a familial component or due to a reset of the thyroid function occurring between the sixth and the eighth decade of life) appears to be related to longevity.

Reference
A cross-section analysis of FT3 age-related changes in a group of old and oldest-old subjects, including centenarians' relatives, shows that a down-regulated thyroid function has a familial component and is related to longevity.
Corsonello A, Montesanto A, Berardelli M, De Rango F, Dato S, Mari V, Mazzei B, Lattanzio F, Passarino G.
Age Ageing. 2010 Sep 15. [Epub ahead of print]
PMID: 20843963

[Guest]

Just to clarify it for me:

assume that I eat a CRON-style diet, so clearly below average kcal-intake (say 1700 kcal instead of the 2400 kcal recommended for people of my size) + ON. I have a "underweight" BMI (say 17) and very low bodyfat.

According to your oppinion, Michael, is it sufficient to just have a look at those measures to confirm one CR-status? Or is it: you need low THS + low body temp. + low to moderate IGF1 etc. and if *just one* of those is missing you are screwed and could as well eat an ad-lib diet. Because eating a very low caloric, balanced diet with a resulting very low BMI is not sufficient in itself to get the alleged CRON-benefits - isn't it?

This is not meant to be sarcastic; just want to point out that all those discussions about tweaking of specific single metabolic features beside the low calory - ON component makes me feel slightly uneasy. The evidence often is even less hard than the evidence for CR-in-humans itself. Or do you seriously believe that people showing every sign of CRON except *one* (be it low IGF1 or low THS or low insuline resistence etc.) will get no benefits at all or neglible ones from a CRON-diet in terms of health/longevity? Isn't CR a multi-systemic, multi-channel effect - acting by influencing a broad variety of processes in the body?

Edited by TFC, 19 October 2010 - 12:44 PM.

[Michael]

Sorry for the delay -- a bit swamped:

assume that I eat a CRON-style diet, so clearly below average kcal-intake [...] + ON. I have a "underweight" BMI (say 17) and very low bodyfat.

According to your oppinion, Michael, is it sufficient to just have a look at those measures to confirm one CR-status? Or is it: you need low THS + low body temp. + low to moderate IGF1 etc. and if *just one* of those is missing you are screwed and could as well eat an ad-lib diet. Because eating a very low caloric, balanced diet with a resulting very low BMI is not sufficient in itself to get the alleged CRON-benefits - isn't it?

Well, clearly there is something about what the body DOES when it's put in a restricted-energy situation that causes to the slow-aging phenotype, and these are all apparent markers -- and likely mediators -- of that slow-aging metabolic state. It may very well be that any one of these mediators, or some interaction thereof, may be essential to the slow-aging effect; alternatively, it may be that they are not mediators, but they are inevitable but causally irrelevant surrogate markers for the metabolic shift in question. But I think that we know far too little about the mechanistic basis of the 'CR effect,' even in rodents, to make a judgement on how important any one of these markers/mediators is; the main thing import of these findings, IMO, is that the general finding that humans & nonhuman primates do tend to respond in the same way as rodents to CR is (a) important as a sign of the likely translatability of the phenomenon, (b) a good place for researchers to probe those mechanisms, and also perhaps to help design or test out mimetics (altho' I think the quest for the CR pill is not going anywhere, and certainly think that the SENS platform will yield faster and therapeutically superior interventions).

That said, I do think they're of some use as personal markers for CR status, for those very reasons. But I don't think we're anywhere near in a state to say with confidence that if you aren't showing one or more of them, then you can't possibly be reaping those benefits. I do think it's worth trying to avoid interfering with those metabolic shifts (eg, by taking hormonal "replacement" therapies to "correct" low testosterone or thyroid hormone levels if you're not suffering unacceptable quality of life symptoms or worryisome associated clinical signs; or by eating a high-protein diet on CR after the initial weight loss period, unless perhaps you're ≥ 60 y.o.; or by getting (much of) your omega-3s from fish and fish oil on CR).

But in my view, provided that you're doing CR in practice, it's quite premature in our current state of relative ignorance to worry about it if your bloodwork isn't responding on some particular parameter.

[Recortes]

more data points here, in case anyone is interested.

I don't really know whether I'm on CR or not. Just from time to time I have 48/72 hour fastings. Of course diet is on the paleo side and have moderate to low BMI. In my last blood test my lipid profile was almost incredibly good for my standards (after doing some changes on diet and supplements) and my thyroid profile is the following , but I've not a clue how to interpretate though




T3 (not specified the type in the test) : 0.76

T4: 6.3

TSH: 2




TSH is really low. I might not be on a large CR but for sure not in a high CR!.

[Mind]

Michael,

I've recently read that 'chubby people' live longer. Is it another datapoint? Given that depressed thyroid functionality can in fact make one chubby.

It has been recently suggested that ALL of the studies (there were several) showing lower mortality for "chubby" people were probably systemically flawed: http://www.longecity..._60#entry564561

[theconomist]

Just a thought and I'm sure it's not that simple: wouldn't hypothyroidism be beneficial in terms of aging because you have a slower metabolism hence need lower ammounts of calories (thus requiring even less calories when performing CR), less protein,carb and fat intake= less of the damage that comes with them.
A 6'4 man with a normal thyroid and metabolism would eat much more than a 5'5 man with hypothyroidism even if both are on CR.

[Annabel]

Out of curiosity...has anyone started CR while already on thyroxine? What happened to your TSH/free-T4? Did you adjust your dose?

[nowayout]

It may be longer but at the cost of feeling miserable.

[Artificiality]

Living longer but at the cost of low-energy and depression just for a few extra years at best? No thanks.

[Matt]

What makes you think we have low energy and depression? I feel the best I've ever felt in my whole life! :o

[Shepard]

Let's keep the posts on-topic, please.

[Julia36]

Just looking at this area.

One dose 25m of levothyroxine and I felt stronger in some ways but realised my metabolism has changed subtly.

I'm feaking sensitive observant OK:)

So looking at some papers on it: seems very complicated.

Low thyroxine can cause probelms eg in the heart, but as posted above, is also associated with longevity
The chain of reasonng makes sese (lower metabolism?)
but I swear the body's far too complex to even take asprin and be abel to predict effects over years.

There are TRILLIONS of combinatorials, including hormones, other pills, symbiotioc bacteria, etc


That obviously doesn't mean we dont try and do the best science, but Im drawn to my tutor's idea of keeping away from all pills (bright at 85).



Roll on machine intelligence, complex enough to model complete human interactions

[DLR]

Thank you for this interesting discussion about Thyroid hormones!

I got some bloodwork done a couple of weeks ago, and I still don't know what to make of them. Unfortunately, they did not test my T3 levels, but my free T4 seems to high and I don't know if this might indicate that I am not practicing CR properly.

Free (direct) T4: 1.5 ng/dL reference range[0.7-1.7]

TSH: 2.5 mcUI/mL reference range [0.3-4.2]



I know my results are not presented in the same units the studies cited, and that is why it is more difficult for me to understand them.

Pre-CR my values were:

TSH: 2,04 mcU/ml
Total T4; 9,33 mcg/dL [reference range: 6-12]
Free T4: (not provided)
total T3: 1,4 ng/ml [reference range: 0.92-2.33]

After starting a very light version of CR my values were:

Free (direct) T4: 1.16 ng/dL
TSH: 2.13 mcUI/mL


It seems my TSH has increased a little bit with CR, but my free T4 levels have increased a lot as well! This is probably a very stupid question but, does this mean I'm eating too much iodine or something that increases my thyroid function? I eat cruciferous vegetables daily, but they are boiled for several minutes (kale is not available in my area, and eating raw broccoli, cauliflower or cabbage is just not something I would like to do in principle) so their goitrogenic effect should be low or non-existent. However, I use salt with iodine and this might increase my thyroid function to dangerous levels. What do you guys think? As I said before, I don't know how to interpret these results and I would appreciate it if you could help me ^^.

[InquilineKea]

Does anyone know if low T3 levels are simply an epiphenomena of calorie restriction, or do they play some causative role in the CR'ed phenotype?

Do T3 levels have any effect on mTOR signalling, for example?

If T3 increases metabolism in the mitochondria, then I'm not sure if that's necessarily "bad" per se. Some increase in oxidative stress can induce hormesis, after all. Also, ACC-mutant mice (http://www.pnas.org/...0/18/10207.full ) do experience higher rates of mitochondrial metabolism as they can't store their carbons as fat, but this seems to only induce hormesis (and they seem to otherwise do as well as normal mice).

[kurdishfella]

can thyroid hormones drugs (t3/t4) help with immune system? Or other metabolism increasing things? etc