Low Serum Free Triiodothyronine Levels Mark Familial Longevity: The Leiden Longevity Study

Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences (Impact Factor: 5.42). 12/2009; 65(4):365-8. DOI: 10.1093/gerona/glp200
Source: PubMed


The hypothalamo-pituitary-thyroid axis has been widely implicated in modulating the aging process. Life extension effects associated with low thyroid hormone levels have been reported in multiple animal models. In human populations, an association was observed between low thyroid function and longevity at old age, but the beneficial effects of low thyroid hormone metabolism at middle age remain elusive.
We have compared serum thyroid hormone function parameters in a group of middle-aged offspring of long-living nonagenarian siblings and a control group of their partners, all participants of the Leiden Longevity Study.
When compared with their partners, the group of offspring of nonagenarian siblings showed a trend toward higher serum thyrotropin levels (1.65 vs157 mU/L, p = .11) in conjunction with lower free thyroxine levels (15.0 vs 15.2 pmol/L, p = .045) and lower free triiodothyronine levels (4.08 vs 4.14 pmol/L, p = .024).
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.

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Available from: Marian Beekman, Oct 09, 2015
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    • "Hypothyroidism may modulate life span by lowering metabolic rate, core body temperature, and oxygen consumption, thereby reducing generation of ROS and associated oxidative damage. Interestingly, subclinical hypothyroidism, (i.e., elevated plasma thyrotropin with lower thyroid hormone concentrations) was associated with reduced mortality in women, is inherited in families with exceptional longevity, and has been linked to a polymorphism in the thyroid-stimulating hormone receptor (37). These studies suggest that thyroid replacement may be unnecessary and potentially even harmful in elderly subjects without clinical hypothyroidism. "
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    • "Unlike earlier observations of difference in glucose, lipid and thyroid metabolism [18], [19], [24], [25], we found no association of levels of homocysteine with familial longevity at middle age in our study population. This finding is in line with the recent debate on the causality of homocysteine in cardiovascular disease. "
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    • "In addition, our observations may imply that the hypothalamo-pituitary-thyroid axis is involved in these features. Indeed, lifespan extension in animal models associates with low activity of the thyroid hormone axis and in our studies we observed that the middle-aged offspring have lower serum-free triiodothyronine levels compared with their middle-aged partners, suggesting that a low thyroid hormone metabolism may contribute to familial longevity at an early age [23]. "
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