Sunday, March 2, 2008

Older News: Sluggish Thyroid Isn't All Bad News... a point, of course. Untreated hypothyroidism is associated with heart problems, but within a presumably healthy range, tipping the lower end of the thyroid hormone scale tends to be associated with longevity:

Here's the scoop:

Longer-lived Rodents Have Lower Levels Of Thyroid Hormone

ScienceDaily (Oct. 12, 2006) — The thyroid may play an important role in longevity, with longer-lived rodents showing significantly lower levels of a thyroid hormone that speeds metabolism, a new study has found.

The study further strengthens the theory that the faster an animal's metabolism, the shorter its life, and vice versa, said Mario Pinto, the study's lead author. The thyroid releases hormones that regulate metabolic rate.

"Thyroid hormones are key regulators of metabolism and have been widely implicated to influence longevity," the authors wrote. Pinto will present the study "Differential thyroid hormone activity in rodents with different life spans" at a poster session Oct. 9 at Comparative Physiology 2006: Integrating Diversity. The study was carried out by Pinto and Rochelle Buffenstein, City College of New York.

Thyroid key to metabolic rate

The thyroid gland produces thyroxine (T4) which converts to triiodothyronine (T3) in the presence of iodine. T3 is the active component of T4 and is the key hormone in regulating metabolism, Pinto said. When an animal becomes cold, for example, its body converts T4 to T3 to speed metabolism and warm the body, he explained.

"Mice strains that exhibit extended longevity tend to have lower thyroid hormone concentrations than shorter living strains," the authors wrote. "Significant declines in thyroid hormone correlate well with enhanced maximum lifespan."

The study compared the levels of these thyroid hormones among four groups of rodents with different life spans: mice, guinea pigs, Damara mole-rats and naked mole-rats. Mice live to about three and a half years; guinea pigs live to six years; Damara mole-rats to 15 years; and naked mole-rats to 28 years.

The animals were of different ages, but at comparable points in their life spans. For example, the mole-rats, which live 28 years, were two years old. The mice, which live about 3.5 years, were six months old. The study determined the levels of T3 and T4 for each animal.

T4 levels vary the most

T4 levels varied significantly between all of the groups, with the shorter-lived groups having higher levels of T4 than longer-lived groups. The mice, for example, had twice as much T4 as the Damara mole-rats and had and three times more than that of the naked mole-rats, Pinto reported. There was also a significant difference in T3 levels between the naked mole-rats and the guinea pigs, but not between any of the other groups

"These hormone concentration differences correlate with maximum species lifespan and suggest an important regulatory role of thyroid hormone in longevity," the researchers concluded. However, because T3, levels did not differ significantly among all the groups, further research in this area using larger sample sizes (numbers of rodents in each group) is needed, Pinto said.

Adapted from materials provided by American Physiological Society, via EurekAlert!, a service of AAAS.

(Emphasis mine).

It's that dang-blasted metabolism again; can't live with it, can't live without it! That which nourishes me also kills me! Et cetera, and so forth, and on. Looks like the best way to extend life is to slow down the speed of life. It's kind of like your life is prerecorded as one film, and you want more of it, you have to watch it in slow-motion. Let's just hope it's more Fellini than 2 Fast 2 Furious, because I wouldn't want the equivalent of stretching out that shitscreen.

In seriousness, I wonder if this also has to do with the sex disparity in longevity. I had long chalked it up to size differences and health habits (women eat healthier, require fewer calories, drink less, take fewer health risks, etc.), but come to think of it, when I worked in a pharmacy, every synthroid-swiper with an underactive thyroid was female, without exception. Those are extreme cases, but I wonder if that's the tail end of a distribution that has most women shifted metabolically in a slow-burning direction. Perhaps estrogen isn't the only culprit for women's greater propensity for fat storage and aversion to weight loss (hello the women of The Biggest Loser!). But perhaps that's why they also make up 85% of all centenarians.

This also lends weight to the possibility that size differences aren't the cause of longevity as much as mutations causing lower growth hormone levels that simultaneously slow aging and reduce size. Note that the tiny mice had higher levels than the larger, longer-lived species with lower levels that correlated with their respective lifespans.

I'm concerned and confused and bewildered in some ways, because the study states that levels of hormone T3 did not appreciably differ between species, whereas its bioactive converted form, T4, did differ and correlate with aging differences. What scares me is that iodine is responsible for this conversion process, and I have seen other studies that implicate dairy intake, one of the greatest dietary sources of iodine, as being a distinctly life-extending food preference among the oldest old. Perhaps it wasn't a lifelong preference, but only adopted later, which beneficially boosts their IGF-1 and thyroid hormones to more youthfully functioning levels (and perhaps prevents muscle wasting as a worthwhile bonus)? I also recall that aboriginal Australians had no trace of cardiovascular disease in spite of largely animal-based sustenance. What was found was that they lacked iodine in their diet, which when supplemented, caused them to grow from their small statures (men were about 5'4", like Asians) to European-typical heights. Without any other changes to their lifestyles, these larger, iodine-ridden folks started developing signs of cardiovascular disease like Europeans as well. I've seen this interpreted as ye olde height problem a-gain, but perhaps it comes down to iodine boosting T3 to T4 conversion, thus boosting metabolism.

Oldish News: Low Glucose Metabolism Reduces Free Radical Damage

Centenarians often have low levels of triglycerides and are lean. Snell dwarf mice have modeled nicely how a beneficial mutation in preferential metabolism can slow the aging process by minimizing the oxidative damage from metabolizing glucose by favoring fat metabolism instead.

From ScienceDaily last November:
--reprinted here:

Fat Hormone May Contribute To Longevity

Altered fasting metabolism may contribute to the
increased longevity of Snell dwarf mice (bottom).
(Credit: Terry Combs)

ScienceDaily (Nov. 23, 2007) — Both humans and mice that manage to live to a ripe, old age show a clear change in their glucose metabolism, but it's unclear whether this change alone can increase lifespan.

Using a mouse model of longevity, Terry Combs and colleagues report that changes in metabolism can indeed increase longevity. They demonstrated that long-lived Snell dwarf mice burn less glucose and more fatty acids during periods of fasting, and as a result produce fewer free radicals.

The key to this switch may be adiponectin, a hormone produced by fat cells that helps lower glucose production and stimulates cells to use fat for energy instead. The researchers found that Snell mice had three times as much adiponectin in their blood as control mice; Snell mice also had fewer triglycerides in their cells, indicative of higher fat metabolism.

The benefit of burning fats instead of glucose for energy is that it produces fewer oxygen radicals which can damage cells and exacerbate the effects of aging. Confirming this, Combs and colleagues found far less free radical damage, measured as the frequency of a chemical modification on protein known as carbonyl groups, in Snell mice than controls.

Article: "Low utilization of circulating glucose after food withdrawal in Snell dwarf mice" by Natasha L. Brooks, Chad M. Trent, Carl F. Raetzsch, Kevin Flurkey, Gunnar Boysen, Michael T. Perfetti, Yo-Chan Jeong, Simon Klebanov, Kajal B. Patel, Valerie R. Khodush, Lawrence L. Kupper, David Carling, James A. Swenberg, David E. Harrison, and Terry P. Combs

Adapted from materials provided by American Society for Biochemistry and Molecular Biology, via EurekAlert!, a service of AAAS.

(Emphasis mine).

I'm wondering if some of the results were confounded by the size differential, i.e., all things equal, smaller animals within most any species tend to live longer than their larger counterparts. Without bothering to delve into the details of the original research paper myself, I'm guessing they're competent enough to correct for body size when evaluating the disparity in longevity.

Note how in true media fashion, the title is accurate but somewhat misleading in regard to the important bit here, which is that any preferential reduction in glucose metabolism in favor of fatty-acid energy sourcing could minimize oxidative stress--no favorable mutations in adiponectin production required.