Steffy W Jansen1, Ferdinand Roelfsema1, Evie van der Spoel1, Abimbola A Akintola1, Iris Postmus1, Bart E Ballieux1, P Eline Slagboom1, Christa M Cobbaert1, Jeroen van der Grond1, Rudi G Westendorp1, Hanno Pijl1, Diana van Heemst1. 1. Departments of Gerontology and Geriatrics (S.W.J., E.v.d.S., A.A.A., I.P., R.G.W., D.v.H.), Endocrinology and Metabolic Diseases (F.R., H.P.), Clinical Chemistry and Laboratory Medicine (B.E.B., C.M.C.), Radiology (J.v.d.G.), and Section of Molecular Epidemiology, Department of Medical Statistics (P.E.S.), Leiden University Medical Center, and Leiden Institute for Brain and Cognition (J.v.d.G.), Leiden University, Albinusdreef 2, 2300 RC Leiden, The Netherlands; and Department of Public Health (R.G.W.), University of Copenhagen, Gothersgade 160, 1123, Denmark.
Abstract
CONTEXT: Longevity is associated with changes in circulating levels of thyroid hormone (TH) and/or TSH in animals and humans, but underlying mechanisms remain elusive. OBJECTIVE: We explored in 38 offspring of nonagenarian participants from the Leiden Longevity Study, who are enriched for longevity and in their partners, ultradian and circadian rhythmicity of TSH, temporal relationship, and feedback and forward interplay between TSH and TH. METHODS: We collected blood samples every 10 minutes for 24 hours for TSH and TH profiles. We used a deconvolution analysis to estimate basal (nonpulsatile), pulsatile, and other secretion parameters to characterize ultradian rhythmicity and locally weighted polynomial regression of TSH to assess circadian rhythmicity. A cross-correlation analysis was used to investigate the temporal relationship between TSH and TH and cross-approximate entropy to assess feedback and forward interplay between TSH and TH. RESULTS: Compared with partners, offspring displayed higher mean (95% confidence interval [CI]) basal TSH secretion (34.3 [95% CI 27.2-43.1] mU/L per 24 hours vs 18.5 [95% CI 14.4-23.7] mU/L per 24 hours, P = .001) but no differences in ultradian or circadian properties of TSH. The temporal relationship between TSH and free T3 at zero delay was higher in offspring (0.48 ± 0.2) compared with partners (0.26 ± 0.4) (P = .05), but the feedback and forward interplay between TSH and TH did not differ. CONCLUSIONS: Familial longevity is associated with increased basal TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH and TH.
CONTEXT: Longevity is associated with changes in circulating levels of thyroid hormone (TH) and/or TSH in animals and humans, but underlying mechanisms remain elusive. OBJECTIVE: We explored in 38 offspring of nonagenarian participants from the Leiden Longevity Study, who are enriched for longevity and in their partners, ultradian and circadian rhythmicity of TSH, temporal relationship, and feedback and forward interplay between TSH and TH. METHODS: We collected blood samples every 10 minutes for 24 hours for TSH and TH profiles. We used a deconvolution analysis to estimate basal (nonpulsatile), pulsatile, and other secretion parameters to characterize ultradian rhythmicity and locally weighted polynomial regression of TSH to assess circadian rhythmicity. A cross-correlation analysis was used to investigate the temporal relationship between TSH and TH and cross-approximate entropy to assess feedback and forward interplay between TSH and TH. RESULTS: Compared with partners, offspring displayed higher mean (95% confidence interval [CI]) basal TSH secretion (34.3 [95% CI 27.2-43.1] mU/L per 24 hours vs 18.5 [95% CI 14.4-23.7] mU/L per 24 hours, P = .001) but no differences in ultradian or circadian properties of TSH. The temporal relationship between TSH and free T3 at zero delay was higher in offspring (0.48 ± 0.2) compared with partners (0.26 ± 0.4) (P = .05), but the feedback and forward interplay between TSH and TH did not differ. CONCLUSIONS: Familial longevity is associated with increased basal TSH secretion and a strong temporal relationship between TSH and free T3 but not with differences in ultradian or circadian TSH rhythmicity or feedback and forward interplay between TSH and TH.
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