about my Hertha Firnberg project ...

Specific aims

We measure energy budgets as well as ROS production of mice from the C57BL6 strain which reproduce repeatedly during their lifespan.
By manipulating ambient temperature and consequently NST each time the animals raise young, we will test if mice with increased uncoupled respiration in the cold live longer than mice with coupled respiration, but equivalent energy turnover.

Also, by comparing the longevity of mice maintained at constant temperature with that of mice exposed to alternating cold and warm temperatures, we will test if metabolic instability impairs lifespan. By having the above described three experimental groups of mice, we thus intend testing the "uncoupled to survive" hypothesis by comparing lifespans of group A and B (see figure).

We will consider this hypothesis as confirmed if the mice of group B of have longer lifespans than mice continuously kept at room temperatures. Further, we will reject the "rate of living" hypothesis if group C (large litter size cold exposed group) will not have a shorter lifespan than the other two groups.
Finally, we will confirm the metabolic stability hypothesis if groups B and C will live shorter than A.

Short final report

"Live fast, die young" refers to the intuitive hypothesis that mammals operate alike machines and wear out the earlier the more they are used.
Thus death from age might occur earlier if metabolism is higher. Indeed, can the aging process occur so easily ?
What role is out there for metabolic stability throughout lifetime ?

To test these frameworks in context with mitochondrial metabolism was the main aim of our study. Mitochondria, as the power houses of cells are most important cell organelles for the metabolism and produce no energy as ATP but heat instead every time they are "uncoupled" which happens when small mammals warm themselves up through nonshivering thermogenesis. During uncoupled respiration mitochondria were also observed to produce less harmful free radicals of oxygen.
We tested in laboratory mice from the strain C 57 Bl/6 if females that raised young at either 15° or 22° C would show altered mitochondrial respiration rates and if this would manifest in lifespan differences. We predicted that lactation under cold conditions would raise a female´s metabolism even further particularly in the experimental group that raised 5 pups. The second experimental group which only raised 3 pups should be observed to have lower energy expenditures and the third group nursing 7 pups at 22° C should have about equal energy budgets. Our experimental protocol aimed to be followed up throughout lifetime of the animals even after reproduction ceases due to age. We in fact observed significant differences in lifespan between the cold exposed and the females at 22° C.
We can thus confirm the "uncoupled to survive" hypothesis as females raising young at 15° C, independent of litter size, had an average lifespan of 644 days, so 74 days longer than in room temperature housed females. Between the mothers raising 5 pups and 3 pups at 15° C; we did however not observe lifespan difference whatsoever and thus have to refute the "Live fast, die young" concept. When isolating liver mitochondria from lactating and non- reproducing females we found that mothers had higher rates of uncoupled respiration.

This result is particularly interesting, as it has become clear meanwhile that females face a physiological limit during reproduction that can only be mitigated with increased heat dissipation to the environment. When testing if females from the different temperatures would have different levels of antioxidant in the blood we observed differences between age classes (in the course of life) but failed to detect differences between experimental groups. We hope that our results will contribute to understand the aging process as well as the physiological costs of reproduction. This aspect is eminent for the animal production field as well as for aging research in general.