Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

Abstract

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

“…These data agree with the positive association between serum TSH levels and longevity reported in rodents [1][2][3] and euthyroid humans [3][4][5][6][7][8][9]. In line with these observations, rhTSH administration in human visceral adipocytes during 7 days, but not In parallel with these findings, a recent publication demonstrated that TSH administration (48h) in fully differentiated human adipocytes resulted in a significant improvement of mitochondrial biogenesis and function, increasing basal respiration, ATP production and spare respiratory capacity in parallel to increased SIRT1 and mitochondrial biogenesisrelated gene markers [22].…”

“…In humans, the relationship between hypothyroidism and increased life expectancy has also been observed [4][5][6][7][8][9]. Euthyroid 50 year-old participants with increased levels of TSH had a longer life expectancy than participants with decreased serum TSH levels [4].…”

“…Increased TSH levels were also associated with lower mortality in participants between ages 85 and 90 [5] and in their offspring [6], and even in centenarians [7,8]. In fact, increased familial longevity is characterized by higher TSH secretion, without altering whole body energy metabolism [9].…”

“…Thyroid function is well known to be involved in longevity and senescence [1][2][3][4][5][6][7][8][9] and in energy balance [10]. Different animal models characterized by increased longevity had in common the following hormonal and metabolic characteristics: 1) reduced thyroid function (absent TSH and severely reduced thyroid hormone in Ames and Snell dwarf mice, in naked mole-rat and calorie-restricted rats), 2) reduced basal metabolic rate, and 3) reduced core body temperature.…”

Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study

“…Notably, the Leiden 85+ study, a cohort study of 85-year-olds with a similar design to our study, found that subclinical hypothyroidism was associated with reduced all-cause mortality and cardiovascular mortality (29). 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. This led us and others to suggest that there may be age-related differences in the vascular risk associated with a raised serum TSH, with higher risks found in younger individuals that attenuated with advancing age (27, 39, 40).…”