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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.

References

  1. Rubner, M. (ed.) Das Problem det Lebensdaur und seiner beziehunger zum Wachstum und Ernarnhung (Oldenberg, 1908).

  2. Harman, D. Aging: a theory based on free radical and radiation biology. J. Gerontol. 11, 298–300 (1956).

    Article  CAS  Google Scholar 

  3. Stark, G., Pincheira-Donoso, D. & Meiri, S. No evidence for the ‘rate of living’ theory across the tetrapod tree of life. Glob. Ecol. Biogeog. 29, 857–884 (2020).

    Article  Google Scholar 

  4. Holmes, D. J., Fluckiger, R. & Austad, S. N. Comparative biology of aging in birds: an update. Exp. Gerontol. 36, 869–883 (2001).

    Article  CAS  Google Scholar 

  5. Austad, S. N. & Fischer, K. E. Mammalian aging, metabolism, and ecology – evidence from the bats and marsupials. J. Gerontol. 46, B47–B53 (1991).

    Article  CAS  Google Scholar 

  6. Speakman, J. R. Body size, energy metabolism and lifespan. J. Exp. Biol. 208, 1717–1730 (2005).

    Article  Google Scholar 

  7. Speakman, J. R. et al. Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3, 87–95 (2004).

    Article  CAS  Google Scholar 

  8. Oklejewicz, M., Hut, R. A., Daan, S., Loudon, A. S. & Stirland, A. J. Metabolic rate changes proportionally to circadian frequency in tau mutant Syrian hamsters. J. Biol. Rhythms 12, 413–422 (1997).

    Article  CAS  Google Scholar 

  9. Brand, M. D. Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp. Gerontol. 35, 811–820 (2000).

    Article  CAS  Google Scholar 

  10. Ramsey, J. J., Harper, M. E. & Weindruch, R. Restriction of energy intake, energy expenditure, and aging. Free Radic. Biol. Med. 29, 946–968 (2000).

    Article  CAS  Google Scholar 

  11. Blanc, S. et al. Energy expenditure of Rhesus monkeys subjected to 11 years of dietary restriction. J. Clin. Endocrinol. Metab. 88, 16–23 (2003).

    Article  CAS  Google Scholar 

  12. Redman, L. M. et al. Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab. 27, 805–815.e4 (2018).

    Article  CAS  Google Scholar 

  13. Daan, S., Deerenberg, C. & Dijkstra, C. Increased daily work precipitates natural death in the kestrel. J. Anim. Ecol. 65, 539–544 (1996).

    Article  Google Scholar 

  14. Pontzer, H. et al. Constrained total energy expenditure and metabolic adaptation to physical activity in adult humans. Curr. Biol. 26, 410–417 (2016).

    Article  CAS  Google Scholar 

  15. Selman, C. et al. Impact of experimentally elevated energy expenditure on oxidative stress and lifespan in the short-tailed field vole, Microtus agrestis. Proc. Biol. Sci. 275, 1907–1916 (2008).

    PubMed  PubMed Central  Google Scholar 

  16. Hollosy, J. O. Minireview – exercise and longevity – studies on rats. J. Gerontol. 43, B149–B151 (1988).

    Article  Google Scholar 

  17. Vaanholt, L. M., Daan, S., Garland, T. & Visser, G. H. Exercising for life? Energy metabolism, body composition and longevity in mice exercising at different intensities. Phys. Biochem. Zool. 83, 239–251 (2010).

    Article  Google Scholar 

  18. Rikke, B. A. et al. Strain variation in the response of body temperature to dietary restriction. Mech. Aging Dev. 124, 663–678 (2003).

    Article  Google Scholar 

  19. Mitchell, S. E. et al. The effects of graded levels of caloric restriction: III. Impact of short-term calorie and protein restriction on mean daily body temperature and torpor use in the C7BL/6 mouse. Oncotarget 6, 18314–18337 (2015).

    Article  Google Scholar 

  20. Cintron-Colon, R. et al. Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction. Proc. Natl Acad. Sci. USA 114, 9731–9736 (2017).

    Article  CAS  Google Scholar 

  21. Froy, O., Chapnik, N. & Miskin, R. Effect of intermittent fasting on circadian rhythms in mice depends on feeding time. Mech. Ageing. Dev. 130, 154–160 (2009).

    Article  CAS  Google Scholar 

  22. Conti, B. et al. Transgenic mice with a reduced core body temperature have an increased life span. Science 314, 825–828 (2006).

    Article  CAS  Google Scholar 

  23. Liao, C. Y. et al. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell 10, 629–639 (2011).

    Article  CAS  Google Scholar 

  24. Speakman, J. R. & Keijer, J. Not so nuanced: Reply to the comments of Gaskill and Garner on ‘Not so hot: Optimal housing temperatures for mice to mimic the environment of humans’. Mol. Metab. 3, 337 (2013).

    Article  Google Scholar 

  25. Gordon, C. J. Thermal physiology of laboratory mice: defining thermoneutrality. J. Therm. Biol. 37, 654–685 (2012).

    Article  Google Scholar 

  26. Zhao, Z. J. et al. The shift of thermoneutral zone in striped hamster acclimated to different temperatures. PLoS ONE 9, e84396 (2014).

    Article  Google Scholar 

  27. Conti, B. Considerations on temperature, longevity and aging. Cell. Mol. Life Sci. 65, 1626–1630 (2008).

    Article  CAS  Google Scholar 

  28. Rikke, B. A. & Johnson, T. E. Lower body temperature as a potential mechanism of life extension in homeotherms. Exp. Gerontol. 39, 927–930 (2004).

    Article  Google Scholar 

  29. Mitchell, S. E. et al. The effects of graded levels of caloric restriction: VIII. Impact of short term calorie and protein restriction on basal metabolic rate in the C57BL.6 mouse. Oncotarget 8, 17453–17474 (2017).

    Article  Google Scholar 

  30. Guijas, C. et al. Metabolic adaptation to calorie restriction. Sci. Signal. 13, eabb2490 (2020).

    Article  CAS  Google Scholar 

  31. Goel, M. K., Khanna, P. & Kishore, J. Understanding survival analysis: Kaplan−Meier estimate. Int. J. Ayurveda Res. 1, 274–278 (2010).

    Article  Google Scholar 

Download references

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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