Extreme Longevity Is Associated with Increased Serum Thyrotropin
Open accessAbstract
CONTEXT: The distribution of serum TSH shifts progressively to higher concentrations with age. OBJECTIVE: The aim of the study was to determine whether the population shift in TSH distribution to higher concentrations with aging extends to people of exceptional longevity, namely centenarians, and to assess the relationship between concentrations of TSH and free T(4) (FT4). DESIGN/SETTING/PATIENTS: We analyzed TSH, FT4, and TSH frequency distribution curves in thyroid disease-free Ashkenazi Jews with exceptional longevity (centenarians; median age, 98 yr), in younger Ashkenazi controls (median age, 72 yr), and in a population of thyroid disease-free individuals (median age, 68 yr) from the U.S. National Health and Nutrition Examination Survey 1998-2002 (NHANES controls). RESULTS: Serum TSH was significantly higher in centenarians [1.97 (0.42-7.15) mIU/liter] than in Ashkenazi controls [1.55 (0.46-4.55) mIU/liter] and NHANES controls [1.61 (0.39-6.29) mIU/liter] (median, 2.5 and 97.5 centiles) (P < 0.001). The TSH frequency distribution curve of centenarians was relatively similar in shape to controls but shifted significantly to higher TSH, including TSH concentration at peak frequency. The TSH distribution curve of the NHANES control group was superimposable to and not significantly different from the Ashkenazi controls. FT4 was similar in centenarians and Ashkenazi controls, and there was a significant inverse correlation between FT4 and TSH in both groups. CONCLUSIONS: 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.
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In individuals with genetically higher TSH concentrations there is enhanced longevity.
“Furthermore, in individuals with genetically higher TSH concentrations there is enhanced longevity.134”
From Hypothyroidism (2024) · cites this paper as [134]
The Abstract reports higher serum TSH in Ashkenazi centenarians than in younger controls, supporting an association with exceptional longevity. The study does not establish that their higher TSH was genetic or that it enhanced longevity; the Discussion describes a favorable role in healthy aging as a possibility and lists other possible explanations for elevated TSH. (LLM, conf=0.87)
Experimental — accuracy not yet measuredStudies in several populations have shown progressively increasing TSH concentrations with age.
“Studies in several populations (Americans, Scottish, Ashkenazi Jews, Chinese) have shown progressively increasing TSH concentrations with age.”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [34]
The 97.5th percentiles of the reference population are considerably higher in the elderly (older than 70 years old) than in younger adults.
“The 97.5th percentiles of the reference population are considerably higher in the elderly (older than 70 years old) than in younger adults [32–35], which is not explained only by higher prevalence of thyroid autoimmunity [36, 37].”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [34]
Longevity was associated with higher TSH concentrations in the Ashkenazi population and confirmed by two Dutch studies.
“Longevity was associated with higher TSH concentrations in the Ashkenazi population (19) and confirmed by two Dutch studies (the Leiden 85-Plus Study and the Leiden Longevity Study) (33–35).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [19]
Studies in the oldest centenarians indicate that individuals with genetically higher TSH concentrations have enhanced longevity.
“Studies in the oldest centenarians indicate that individuals with genetically higher TSH concentrations have enhanced longevity [105].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [105]
Up to 3% of older individuals have a serum TSH concentration below the healthy reference interval for younger people (subclinical hyperthyroidism), and approximately 10% have an elevated serum TSH level (subclinical hypothyroidism).
“However, this topic has taken on increasing significance, given that it has been recognized that up to 3% of older individuals have a serum TSH concentration that is below the healthy reference interval for younger people (subclinical hyperthyroidism), and approximately 10% have an elevated serum TSH level (subclinical hypothyroidism) (4–7).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [7]
An elevated serum TSH may be positively associated with longevity and favorable outcomes in the very old.
“This finding, along with the results of familial studies of the oldest old (7, 38), suggests that an elevated serum TSH may be positively associated with longevity and favorable outcomes in the very old.”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [7]
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- Authors
- Atzmon, G., Barzilai, N., Hollowell, J. G., Surks, M. I., & Gabriely, I.
- Affiliations
- Albert Einstein College of Medicine (US)
- University of Kansas Medical Center (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-04
- Volume
- 94
- Issue
- 4
- Pages
- 1251-1254
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2682478
- OpenAlex
- W2038826776
- Cited by
- 260
- References
- 20
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 8 · 2023: 13 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 16 · 2018: 19 · 2017: 20 · 2016: 13 · 2015: 14 · 2014: 17 · 2013: 35 · 2012: 28
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG018728, AG027734, P01AG027734, AG-18728)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK20541, P60DK020541, P30DK020541)
- National Center for Research Resources (M01-RR12248, M01RR012248, RR-12248)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- serum thyrotropin, centenarians, exceptional longevity, aging, free thyroxine, Ashkenazi Jews, thyroid function
- MeSH terms
- Aged, 80 and over, Female, Health Surveys, Humans, Hypothyroidism, Jews, Longevity, Male, New York City, Thyrotropin, Thyroxine
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