Impaired thermogenesis is one of the features of normal ageing. MtDNA mutator mice expressing defective mtDNA polymerase exhibit several features of premature aging and reduced lifespan [1]. The observed phenotype in mtDNA mutator mice is a direct consequence of the accumulation of mtDNA point mutations, leading to a decreased assembly of the respiratory chain complexes and thus to mitochondrial dysfunction [2]. The aim of the present study was to explore the brown adipose tissue (BAT) function and related thermogenesis in this mouse model of premature ageing. MtDNA mutator mice had low body temperature measured rectally with a Microprobe Thermometer (as in [3]). Low body temperatures were evident at both room environment and thermoneutrality suggesting an anapyrexia (regulated decrease in defended body temperature). The hypothermia (inability to compensate for heat loss) was also identified as the reason for lowered body temperature of these mice. During gradually decreasing the environmental temperature in the metabolic chamber, wild type (WT) mice responded by adequate increase in thermogenesis, whereas mtDNA mutator mice were unable to further increase their metabolism at environmental temperatures below 24 °C and went into torpor. We also examined potential recruitment of BAT by measuring oxygen consumption in mice in response to sympathetic stimulus, norepinephrine (NE), subcutaneously injected in dose 1 mg per kg body weight as it was described in [3]). MtDNA mutator mice at 30 °C responded to NE with a lower level as compared with the level of NE response at 22 °C, indicating preserved central regulation of recruitment in these mice. However, magnitudes of NE-response in mtDNA mutator mice were much lower as compared with response in WT mice. Normal sympathetic signalling was confirmed by normal changes in morphology of BAT at 30 °C (few large unilocular lipid droplets in cytoplasm of brown adipocytes) as compared with 22 °C (numerous small multilocular lipid droplets in cytoplasm). However, the thermogenic capacity of BAT was significantly reduced in mtDNA mutator mice: the total protein content in BAT was 41% lower in mtDNA mutator mice than in WT mice. As compared with wild-type mitochondria, on all 3 substrates investigated (pyruvate, palmitoyl-l-carnitine and glycerol-3-phosphate), UCP1-dependent oxygen consumption was significantly reduced in isolated mtDNA mutant mitochondria as was maximal oxidative capacity (FCCP-response) indicating impaired thermogenesis on the level of brown-fat mitochondria in mtDNA mutator mice, although UCP1 content was preserved. Thus, mtDNA mutation led to lower activity of brown adipose tissue and impaired thermogenesis; i.e. also in this respect, mtDNA mutator mice mimicked normal ageing.