Extreme Longevity Is Associated with Increased Serum Thyrotropin

Atzmon, Gil; Barzilai, Nir; Hollowell, Joseph G.; Surks, Martin I.; Gabriely, Ilan

doi:10.1210/jc.2008-2325

Cited by 220 publications

(157 citation statements)

References 22 publications

(22 reference statements)

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“…Indeed, high levels of TSH (Gussekloo et al 2004) and low levels of FT4 (van den Beld et al 2005) are associated with a better survival in elderly subjects. In addition, centenarians and centenarians' offspring have higher levels of TSH compared with controls (Atzmon et al 2009a;Atzmon et al 2009b). Interestingly, thyroid failure may induce a suppression in several processes involved in nucleotide biosynthesis and DNA replication (Agocha et al 1997;Ledda-Columbano et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring

Gentilini

Mari

Castaldi

et al. 2012

AGE

180

123

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The role of epigenetics in the modulation of longevity has not been studied in humans. To this aim, (1) we evaluated the DNA methylation from peripheral leukocytes of 21 female centenarians, their 21 female offspring, 21 offspring of both non-long-lived parents, and 21 young women through ELISA assay, pyrosequencing analysis of Alu sequences, and quantification of methylation in CpG repeats outside CpG AGE (2013) 35:1961-1973 DOI 10.1007 islands; (2) we compared the DNA methylation profiles of these populations through Infinium array for genome-wide CpG methylation analysis. We observed an age-related decrease in global DNA methylation and a delay of this process in centenarians' offspring. Interestingly, literature data suggest a link between the loss of DNA methylation observed during aging and the development of age-associated diseases. Genomewide methylation analysis evidenced DNA methylation profiles specific for aging and longevity: (1) aging-associated DNA hypermethylation occurs predominantly in genes involved in the development of anatomical structures, organs, and multicellular organisms and in the regulation of transcription; (2) genes involved in nucleotide biosynthesis, metabolism, and control of signal transmission are differently methylated between centenarians' offspring and offspring of both non-long-lived parents, hypothesizing a role for these genes in human longevity. Our results suggest that a better preservation of DNA methylation status, a slower cell growing/metabolism, and a better control in signal transmission through epigenetic mechanisms may be involved in the process of human longevity. These data fit well with the observations related to the beneficial effects of mild hypothyroidism and insulinlike growth factor I system impairment on the modulation of human lifespan.

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Section: Discussionmentioning

confidence: 99%

Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring

Gentilini

Mari

Castaldi

et al. 2012

AGE

180

123

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“…The TSHR gene and longevity Atzmon et al (83) reported and confirmed that exceptional longevity is associated with increased serum TSH. Their further study (84) measured serum TSH and free T 4 in Ashkenazi Jewish centenarians (n ¼ 232; median age, 97 years), their offspring (n ¼ 366; median age, 69 years), and age-matched controls without familial longevity (n ¼ 163; median age, 70 years).…”

Section: The Tshr Gene and Thyroid Neoplasmsmentioning

confidence: 92%

The Genetics of the Thyroid Stimulating Hormone Receptor: History and Relevance

Davies

Yin

Latif

2010

Thyroid

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“…This study did not resolve the question whether the decreased FT3 and TSH value observed in healthy centenarians, represents an adaptive mechanism to reduced metabolic homeostasis or a protective condition in ageing. At partial odds with these data, a population based survey and one large cross-sectional study (Atzmon et al, 2009;Surks et al, 2007) showed a progressive shift of the normal serum TSH range towards higher values from healthy young individuals up to centenarians. Overall these data seem to suggest that ageing is associated with a certain degree of down regulation of the hypothalamuspituitary-thyroid-peripheral axis, although the clinical significance of such condition is far to be elucidated.…”

Section: Thyroid Function and Ageingmentioning

confidence: 97%