Researchers at the Buck Institute for Research on Aging have published the results of a longitudinal and functional study of 700 aging mice [1]. The study took several years to complete, with five of the labs at the Buck collaborating.
As part of this detailed study, the research team monitored rates of age-related change using clinically important parameters such as blood glucose, body composition changes, remodelling of the spine, activity levels, metabolic changes, and aging of bone structure in untreated mice. This in-depth analysis of aging in mice is a world first and provides a highly detailed picture of how these animals age.
Understanding how mice age at this high level of detail should serve as an excellent baseline when researchers test interventions that target the aging processes. Any deviations from the detailed patterns of aging recorded in these mice should be immediately noticeable and could help in the development of treatments that aim to reverse or slow down aging.
The researchers also tested a number of potential drugs that had been shown to increase lifespan in simple model organisms as well as ones that had previously been shown to reduce the impact of neurological diseases in mice.
They discovered that benzoxazole was able to slow down the rate of bone aging by up to 31% during a year of treatment. Benzoxazole was originally identified as a compound that was able to increase the lifespan of nematodes during a 2011 study at the Lithgow lab at the Buck.
It was somewhat of a surprise to the researchers that benzoxazole slowed down bone aging, given that it extended the lifespan of an animal that had no bones. These results suggest there are pathways of aging that are evolutionarily conserved.
The researchers are continuing to investigate how benzoxazole achieves this slowing down of bone aging, but so far it appears that it slows down the reabsorption of osteoclasts, which support bone growth.
The findings of this study are not only useful for animal research but for humans as well, as the metrics and biomarkers that the researchers chose during the study are not just relevant to mouse aging, as they also have direct clinical versions of what other researchers would measure in humans.
The online database they created as part of this study could be a highly useful resource for researchers wishing to test if an intervention influences aging and to provide information on how many mice are needed and how long results would take. You can access the online database application now.
Aging is characterized by systemic declines in tissue and organ functions. Interventions that slow these declines represent promising therapeutics to protect against age‐related disease and improve the quality of life. We tested several interventions associated with lifespan extension in invertebrates or improvement of age‐related disease in mouse models to determine if they were effective in slowing tissue aging in a broad spectrum of functional assays. We found that benzoxazole, which extends the lifespan of C. elegans, slowed age‐related femoral bone loss in mice. We also established rates of change for clinically significant parameters in untreated mice, including kyphosis, blood glucose, body composition, activity, metabolic measures, and detailed parameters of skeletal aging in bone. These findings have implications for the study of pre‐clinical physiological aging and therapies targeting aging. Finally, we created an online application that includes the calculated rates of change and that enables power and variance to be calculated for many clinically important metrics of aging with an emphasis on bone. This resource will help in future study designs employing novel interventions in aging mice.
Conclusion
The more tools researchers have at their disposal, the better on the long road to developing treatments that can delay, slow, or even reverse aging. The Buck is doing some truly excellent foundational research on aging that supports other labs in developing interventions that may one day change how we age.
Literature
[1] Evans, D. S., O’Leary, M. N., Murphy, R., Schmidt, M., Koenig, K., Presley, M., … & Melov, S. Longitudinal Functional Study of Murine Aging: A Resource for Future Study Designs. JBMR Plus, e10466.
