Exp Gerontol. 2017 Jan;87(Pt B):139-147 

Sex-related differences in the wheel-running activity of mice decline with increasing age.

Bartling B1, Al-Robaiy S2, Lehnich H3, Binder L2, Hiebl B3, Simm A4 

1Department of Cardiac Surgery, Middle German Heart Centre, University Hospital Halle (Saale), Halle (Saale), Germany. Electronic address: babett.bartling@uk-halle.de.

2Department of Cardiac Surgery, Middle German Heart Centre, University Hospital Halle (Saale), Halle (Saale), Germany.

3Centre of Medical Basic Research, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

4Department of Cardiac Surgery, Middle German Heart Centre, University Hospital Halle (Saale), Halle (Saale), Germany; Centre of Medical Basic Research, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.



Laboratory mice of both sexes having free access to running wheels are commonly used to study mechanisms underlying the beneficial effects of physical exercise on health and aging in human. However, comparative wheel-running activity profiles of male and female mice for a long period of time in which increasing age plays an additional role are unknown. Therefore, we permanently recorded the wheel-running activity (i.e., total distance, median velocity, time of breaks) of female and male mice until 9months of age. Our records indicated higher wheel-running distances for females than males which were highest in 2-month-old mice. This was mainly reached by higher running velocities of the females and not by longer running times. However, the sex-related differences declined in parallel to the age-associated reduction in wheel-running activities. Female mice also showed more variances between the weekly running distances than males, which were recorded most often for females being 4-6months old but not older. Additional records of 24-month-old mice of both sexes indicated highly reduced wheel-running activities at old age. Surprisingly, this reduction at old age resulted mainly from lower running velocities and not from shorter running times. Old mice also differed in their course of night activity which peaked later compared to younger mice. In summary, we demonstrated the influence of sex on the age-dependent activity profile of mice which is somewhat contrasting to humans, and this has to be considered when transferring exercise-mediated mechanism from mouse to human.

Keywords: Activity; Age; Mouse; Sex; Wheel running

PMID: 27108181

DOI: 10.1016/j.exger.2016.04.011



Most dangerous exercise is no exercise because our human body is genetically determined to move. Not all the day but much more than normally done in the Western world. The relatively low exercise in duration and intensiveness is one important reason for the increase in certain diseases, especially diseases of the cardio-vascular or musculoskeletal system and metabolic diseases. For that reason, a large number of studies have been initiated to investigate the impact of exercise – endurance and strength sports – on general health and defined diseases. This includes not only human studies but also animal studies mainly using mice and rats as species and running wheels for promoting higher physical activity. Despite some limitations [1] animal studies are of high importance because they can better exclude some environmental impacts than human studies can do.


Factors of the Western life style responsible for our relatively low exercise each day are well known but what about our natural desire for exercise? Intrinsic and extrinsic factors most likely influencing our motivation to move are summarized in figure 1. Since the natural desire for exercise of human individuals is strongly influenced by the modern lifestyle, animal studies might well contribute to answer this question. In this regard, wheel-running studies of Lerman et al. 2002 [2] and Lightfoot et al. 2004 [3] using different mouse strains indicated the strong impact of the genetic background on the natural desire for exercise. Mice genetically determined to run long distances might therefore develop a better physical conditions which again promotes health. The relation between running activity and health is also suggested by the study of Holloszy et al. 1985 showing in a rat model that the runners lived slightly longer than the sedentary rat [4]. As a part of the genetic background also the sex plays a significant role. This has been demonstrated by the studies of Koteja et al. 1999 [5] and Lightfoot et al. 2004 [3] and also by our work. We and the other two studies found consistently out that young female mice run longer distances than male mice do. The longer running distances of the females were reached more by higher running velocities than by less running-free periods. Especially the higher velocities reached by female than male mice are opposite to the sex-dependent differences in the running velocity for short and long distances of humans [6, 7]. Detailed evaluations of the running profile of our mice also identified strong periodical changes in the running distance, which were significantly higher for females than males. In other words, female mice can run very high distances in one week followed by another week of much lower distances. It is well conceivable that they need a relatively more pronounced refractory phase from their high physical strain and/or have problems with their motivation to run at such high levels. Also, the estrus cycle of female mice seems to influence their activity pattern [8]. With increasing age the running activities of males and females decline and the sex-dependent differences in the activity pattern become smaller (Fig. 2). Therefore, three main conclusions can be drawn from our observations:

  • Sex-dependent differences in the running velocity cannot be transferred to humans, which is one important limitation of exercise models using mice and eventually other animals.
  • Sex-dependent differences in the running velocity of mice are depending on age, which must be considered when performing exercise models using mice.
  • Wheel-running experiments should be performed for longer time periods because the running velocity, especially of female mice, can vary strongly from week to week.


In old age the distance run by mice is significantly reduced which was also shown by other studies, for example Cheng et al. 2013 [9]. One might think that the lower running distance of old mice is based on both, less running velocity and take of more and longer breaks, but this was not fully the case. Although old mice of our study showed a reduced desire for exercise in a running wheel than young mice, their wheel-running use was comparable with adult mice. They just run less fast and reached the maximum activity later in their active (night) phase. Altogether our animal study suggests that the motivation to move is per se not restricted by aging. Factors like genetic background, health status and environment might play a more critical role in the age-related decline of physical exercise of many individuals.



Fig. 1. Numerous intrinsic and extrinsic factors influencing the exercise activity of individuals.

Fig. 2. Simplified presentation of the sex-dependent voluntary wheel-running activity of mice with increasing age.





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