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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 the citing paper
“Furthermore, in individuals with genetically higher TSH concentrations there is enhanced longevity.134”
From Hypothyroidism (2024) · cites this paper as [134]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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Cites
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Self-citationSubclinical Thyroid Disease: Scientific Review and Guidelines for Diagnosis and Management
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Self-citationThe Clinical Significance of Subclinical Thyroid Dysfunction
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Dwarf mice and the ageing process
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Thyroid Status, Disability and Cognitive Function, and Survival in Old Age
Gussekloo, J. (2004) · JAMA · doi:10.1001/jama.292.21.2591 · Cited by 899
Surks, M. I., & Hollowell, J. G. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1499 · Cited by 750
Self-citationUnique Lipoprotein Phenotype and Genotype Associated With Exceptional Longevity
Barzilai, N. (2003) · JAMA · doi:10.1001/jama.290.15.2030 · Cited by 578
Self-citationMeta-analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality
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Cited by
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2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803
Self-citationAge-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort
Bremner, A. P., Feddema, P., Leedman, P. J., Brown, S. J., Beilby, J. P., Lim, E. M., Wilson, S. G., O'Leary, P. C., & Walsh, J. P. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3020 · Cited by 336
Selmer, C., Olesen, J. B., Hansen, M. L., Lindhardsen, J., Olsen, A.-M. S., Madsen, J. C., Faber, J., Hansen, P. R., Pedersen, O. D., Torp-Pedersen, C., et al. (2012) · BMJ · doi:10.1136/bmj.e7895 · Cited by 323
Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring
Horvath, S., Pirazzini, C., Bacalini, M. G., Gentilini, D., Di Blasio, A. M., Delledonne, M., Mari, D., Arosio, B., Monti, D., Passarino, G., et al. (2015) · Aging · doi:10.18632/aging.100861 · Cited by 316
Metadata
- 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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