Human Longevity Is Characterized By Higher Total Thyroid Stimulating Hormone Secretion and Similar Levels of Thyroid Hormone

Presentation Number: OR11-6
Date of Presentation: March 5th, 2015

Steffy Wilhelmina Jansen1, Abimbola Akintola1, Ferdinand Roelfsema2, Evie van der Spoel1, Christa M Cobbaert2, Bart EPB Ballieux1, Peter Egri3, Zsuzanna Kvarta-Papp3, Balazs Gereben3, Csaba Fekete4, Petronella E. Slagboom1, Jeroen van der Grond5, Barbara Demeneix6, Hanno Pijl2, Rudi G J Westendorp1 and Diana van Heemst*1
1Leiden University Medical Center, Netherlands, 2Leiden University Medical Center, Leiden, Netherlands, 3Hungarian Academy of Sciences, Hungary, 4Institute of Experimental Medicine, Budapest, Hungary, 5Leiden University Medical Center, 6Muséum National d'Histoire Naturelle, Paris CEDEX 05, France

Abstract

Only few studies have included subjects with a propensity to reach old age in good health, aiming to disentangle mechanisms contributing to staying healthier for longer. Greater longevity has been associated with higher TSH levels in humans and lower thyroid hormones (TH) levels in animals(1), but the mechanisms underlying TSH/TH differences and longevity are unknown. In this study, we assessed TSH and thyroid hormone regulation in relation with familial longevity. We included 112 subject of the Leiden Longevity study cohort consisting of 61 middle-aged offspring of nonagenarian siblings (offspring) together with 51 of their partners (controls) not originated from long-lived families. All subjects underwent measurements of energy metabolism consisting of an indirect calorimetry measurement and continuous core body temperature measurements. We measured bone resorption and bone formation markers as indicators of bone tissue turnover. In a subset of 20 offspring and 18 controls, blood was frequently sampled over 24 hours, from which circulating TSH levels were measured every 10 minutes and levels of TH every hour. Using deconvolution analysis specific features of HTP-axis function were assessed, including secretion rates, number of pulses, and regularity of pulses. Total geometric mean (95% confidence interval (CI)) TSH secretion was significantly (P < 0.007) higher in the offspring (55.0 (43.9-68.9) mU/l/24h) compared to the controls (34.4 (27.1-43.7) mU/l/24h). In line, offspring had on average, 0.8 mU/L higher serum levels of TSH at all time points. In contrast, circulating TH levels were similar between groups. TSH bioactivity was determined by measuring cAMP production in cultured Chinese hamster ovary cells stably transfected with the human TSH receptor. Offspring and partners had similar cAMP/TSH ratios indicating that their TSH molecules had similar bioactivity. Offspring and controls had similar resting metabolic rate and core body temperature. However, mean (95% CI) levels of the bone resorption marker beta-crosslaps were significantly (P = 0.02) lower in offspring (0.30 (0.28-0.34) ng/ml) compared to controls (0.36 (0.33-0.40) ng/ml), indicating a decreased bone turnover. Moreover, markers of bone renewal also tended to be lower in offspring from long-lived siblings. In conclusion, offspring of exceptionally long-lived humans are characterized by high total TSH secretion, decreased bone turnover, without changes in energy metabolism or circulating TH levels. We propose that pleiotropic effects of differences in thyroid status favor longevity by slowing rates of tissue turnover, without altering whole body metabolism. Our findings provide new targets for studying mechanisms to improve healthy life expectancy, including experimental studies to determine the effects of TSH on tissue regeneration and repair.

 

Nothing to Disclose: SWJ, AA, FR, EV, CMC, BEB, PE, ZK, BG, CF, PES, JV, BD, HP, RGJW, DV