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Body temperature is a more important modulator of lifespan than metabolic rate in two small mammals

Nature Metabolism volume 4, pages 320–326 (2022)Cite this article

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Abstract

The relationships between metabolic rate, body temperature (Tb), body composition and ageing are complex, and not fully resolved. In particular, Tb and metabolic rate often change in parallel, making disentangling their effects difficult. Here we show that in both sexes of mice and hamsters exposure to a temperature of 32.5 °C leads to a reduced lifespan, coincident with lowered metabolic rate and elevated Tb with no change in body composition. We exploit the unique situation that when small mammals are exposed to hot ambient temperatures their Tb goes up, at the same time that their metabolic rate goes down, allowing us to experimentally separate the impacts of Tb and metabolic rate on lifespan. The impact of ambient temperature on lifespan can be reversed by exposing the animals to elevated heat loss by forced convection, which reverses the effect on Tb but does not affect metabolic rate, demonstrating the causal effect of Tb on lifespan under laboratory conditions for these models. The impact of manipulations such as calorie restriction that increase lifespan may be mediated via effects on Tb, and measuring Tb may be a useful screening tool for putative therapeutics to extend the human lifespan.

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Fig. 1: Survival curves, mortality curves and lifespan.
Fig. 2: Body mass and food intake.
Fig. 3: Daily energy expenditure.
Fig. 4: Body temperature.

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Data availability

All additional data supporting the findings of this study are publicly available on the open science framework (http://osf.io.e7baj; https://doi.org/10.17605/OSF.IO/4FUJ7). Source data are provided with this paper.

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Acknowledgements

We thank J.-X. Yu and G.-M. Deng from Wenzhou University for their assistance with animal care. This work was partly supported by grants (31670417 and 31870388 to Z.Z., and 92057206 to J.R.S.) from the National Natural Science Foundation of China and the National Key R&D Program of China (2019YFA0801900 to J.R.S.).

Author information

Authors and Affiliations

  1. School of Life and Environmental Sciences, Wenzhou University, Wenzhou, China

    Zhijun Zhao, Jing Cao, Menghuan Bao, Jiaqi Xu, Daliang Huo, Shasha Liao & Wei Liu

  2. School of Agricultural Science, Liaocheng University, Liaocheng, China

    Zhijun Zhao & Jing Cao

  3. Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Chaoqun Niu & John R. Speakman

  4. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK

    Chaoqun Niu & John R. Speakman

  5. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

    Chaoqun Niu & John R. Speakman

Authors
  1. Zhijun Zhao
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Contributions

Z.Z. and J.R.S. designed research; Z.Z., J.C., C.N., M.B., J.X., D.H., S.L. and W.L. the performed research. Z.Z. and J.C. analysed the data. Z.Z. and J.R.S. wrote the paper.

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Correspondence to Zhijun Zhao or John R. Speakman.

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The authors declare no competing interests.

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Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editor: Isabella Samuelson

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Extended data

Extended Data Fig. 1 Locomotor behavior.

a, b, c and d. The locomotor behaviour over 48 h of striped hamster and Swiss mice. Shown are means ± s.e.m. of female hamsters, 21 °C, n=11, 32.5 °C, n=10, 32.5 °C+W, n=10, and male hamsters, 21 °C, n=10, 32.5 °C, n=12, 32.5 °C +W, n=12; and female mice, n=10 per group, and male mice, 21 °C, n=10, 32.5 °C, n=12, 32.5 °C +W, n=11 of biologically independent samples. e, f, g and h. The average locomotor behaviour over the dark and light phases. Shown are individual values, means ± SD of female hamsters, 21 °C, n=11, 32.5 °C, n=10, 32.5 °C+W, n=10, and male hamsters, 21 °C, n=10, 32.5 °C, n=12, 32.5 °C +W, n=12; and female mice, n=10 per group, and male mice, 21 °C, n=10, 32.5 °C, n=12, 32.5 °C +W, n=11 of biologically independent samples. Statistical significance was determined by one-way ANOVA (one-sided), followed by Tukey post-hoc tests. Black bars, dark phase; blank bars, light phase. Both rodents in the 32.5 °C and 32.5 °C +W groups showed similar circadian pattern of locomotor behavior to those in the 21 °C group, increasing in dark phase in the night, and decreasing in light phase in the day (Extended Data Fig. 1a–d). The average locomotor counts of female hamsters did not differ significantly between the three groups over the dark (F2,28=2.60, P=0.092), but it did over the light (Extended Data Fig. 1e). The average locomotor counts of male hamsters differed significantly among the three groups (Extended Data Fig. 1f). The average locomotor counts of female mice did not differ significantly between the three groups (dark: F2,27=2.58, P=0.094; light: F2,27=0.01, P=0.999, Extended Data Fig. 1g). The average locomotor counts of male mice was significantly lower at 32.5 °C than that at 21 °C over the dark, whereas it was not significantly different between the three groups over the light (F2,31=1.37, P=0.270, Extended Data Fig. 1h).

Source data

Extended Data Fig. 2 Serum IL-6 and TNFa concentration.

a, b, c and d. Serum IL-6 concentration of striped hamsters and Swiss mice. Shown are individual values, means ± SD of female hamsters, n=7 per group, and male hamsters, 21 °C, n=7, 32.5 °C, n=7, 32.5 °C+W, n=6; and female mice, n=7 per group, and male mice, 21 °C, n=7, 32.5 °C, n=7, 32.5 °C+W, n=6 biologically independent samples. Statistical significance was determined by one-way ANOVA (one-sided). e, f, g and h. Serum TNFa concentration of striped hamsters and Swiss mice. Shown are individual values, means ± SD of female hamsters, n=7 per group, and male hamsters, 21 °C, n=7, 32.5 °C, n=7, 32.5 °C+W, n=6; and female mice, n=7 per group, and male mice, 21 °C, n=7, 32.5 °C, n=7, 32.5 °C+W, n=6 biologically independent samples. Statistical significance was determined by one-way ANOVA (one-sided). Serum IL-6 concentration did not significantly differ between the 21 °C, 32.5 °C and 32.5 °C+W groups for either hamsters (females, F2,18=0.34, P=0.716, Extended Data Fig. 2a; males, F2,17=0.13, P=0.880, Extended Data Fig. 2b) or mice (females, F2,18=0.26, P=0.772, Extended Data Fig. 2c; males, F2,17=0.25, P=0.781, Extended Data Fig. 2d). Also, there was no significant difference in serum IL-6 concentration between the three groups for either hamsters (females, F2,18=0.04, P=0.964, Extended Data Fig. 2e; males, F2,17=0.11, P=0.898, Extended Data Fig. 2f) or mice (females, F2,18=0.10, P=0.909, Extended Data Fig. 2g; males, F2,17=0.06, P=0.943, Extended Data Fig. 2h).

Source data

Supplementary information

Supplementary Information

Supplementary Tables 1 and 2.

Reporting Summary

Source data

Source Data Fig. 1

Survivorship and mortality.

Source Data Fig. 2

Body mass and food intake.

Source Data Fig. 3

Daily energy expenditure (DEE).

Source Data Fig. 4

Body temperature (Tb).

Source Data Extended Fig. 1

Locomotor behavior.

Source Data Extended Fig. 2

Serum IL-6 and TNFα concentration.

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Zhao, Z., Cao, J., Niu, C. et al. Body temperature is a more important modulator of lifespan than metabolic rate in two small mammals. Nat Metab 4, 320–326 (2022). https://doi.org/10.1038/s42255-022-00545-5

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