Caloric Restriction Retards the Age-Related Decline in Mitochondrial Function of Brown Adipose Tissue

Abstract

Caloric restriction (CR) has been shown to prevent the age-associated loss of mitochondrial function and biogenesis in several tissues such as liver, heart, and skeletal muscle. However, little is known about the effects of CR on a tissue in which the mitochondria have no adenosine triphosphate (ATP)-producing purpose but show a high degree of uncoupling, namely brown adipose tissue (BAT). Hence, the aim of the present study was to analyze the effect of long-term CR on BAT mitochondrial function and biogenesis. BAT mitochondria obtained from 24-month-old male and female rats previously subjected to 40% CR for 12 months were compared with mitochondria from old (24 months) and young (6 months) ad libitum fed rats. Old restricted rats compared to old ad libitum fed ones showed a reduction in BAT size with respect to fat content and adipocyte number. Mitochondrial DNA content in BAT increased with age and even more so in restricted rats, indicating a summative effect of age and CR on mitochondrial proliferation. CR induced resistance to lose total and mitochondrial protein, COX activity, and uncoupling capacity with advancing age, in relation with a lower decrease of mitochondrial transcription factor A (TFAM). In summary, our results demonstrate CR prevents the age-associated decline in mitochondrial function in BAT, probably in relation with a lower impairment of mitochondrial biogenesis.