However, when the centenarians' data were(26, 28). Taken together, animal models of longevity demonstrate that hypothyroidism, and the accompanying metabolic consequences of hypothyroidism, play a central physiological role in life. A limitation of our study is that, at present, our findings and conclusions are restricted to the Ashkenazi Jewish population and cannot be generalized to other populations. Clearly, genetic studies in non-Ashkenazi populations in North America would be of great interest in this regard. Others have reported on serum TSH in individuals of exceptional longevity, some showing increased concentrations (2, 31) and others showing decreased concentrations (32, 33). None have reported on genetic changes as in the present work. We suggest that those reported studies be interpreted cautiously because the study populations were small, have different genetic backgrounds from our study groups, and live in areas of variable iodine supply. Another limitation is that, because of the lack of availability of serum in some individuals, we could not examine the relationship between FT4 and TSH in the entire control and offspring groups. In our Ashkenazi populations, the higher serum TSH concentrations in the centenarian group and their offspring suggest that they might have a small degree of hypothyroidism, possibly subclinical hypothyroidism. Because nonthyroidal disease may decrease serum TSH, an alternative but less likely possibility is that the centenarians were in better overall health than the control group (34). Subclinical hypothyroidism is defined as raised serum TSH in association with normal FT4 and it occurs in millions of people, particularly the elderly (1). The prevalence of TSH above 4.5 mIU/liter is less than 2% in people without known thyroid disease who are between 20 and 60 years of age and rises steeply to 15% in individuals older than 80 years of age (1). Because of population shifts in TSH distribution to higher concentrations with age, the serum TSH of 70% of those elderly individuals with TSH above 4.5 mIU/liter, who are currently considered to have subclinical hypothyroidism, actually falls within their age-specific limits (4). These recent reports suggest that only a minority of elderly individuals with minimally raised serum TSH may have thyroid disease. Our present findings of a genetic basis for raised TSH in the Ashkenazi population with exceptional longevity, if extended to other populations in future studies, suggest that this change could be protective and, as a corollary to that speculation, that routine levothyroxine treatment might be harmful.

Acknowledgments: The authors thank Ms. Zhao Hu and Mr. Temuri Bodagov for laboratory determinations, and Drs. Govindaraju R. Diddahally and Swapnil Rajpathak for reviewing and commenting on this article.

Address all correspondence and requests for reprints to: Ilan Gabriely, 1300 Morris Park Avenue, Belfer Building, Suite 707.

This work was supported by Grants AG-027734, AG-18728, RR-12248, DK-20541, and U19 AG023122 from the National Institute on Aging Longevity Consortium and by M01-RR12248 from the National Institutes of Health and the Glenn Foundation.

Disclosure Summary: The authors have nothing to disclose.

References:

Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87: 489-499, 2002.

Tietz NW, Shuey DF, Wekstein DR. Laboratory values in fit aging individuals-sexagenarians through centenarians. Clin Chem 41: 822-823, 1995.

Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA 292: 2591-2599, 2004.

Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab 92: 4575-4582, 2007.

Boucai L, Surks MI. Reference limits of serum thyrotropin (TSH) and free thyroxine (free T4) are significantly influenced by race and age in an urban outpatient practice of medicine. Clin Endocrinol (Oxf) 70: 788-793, 2009.

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