Common Laboratory Mice Age Faster in a Natural Environment

Recent research published in Aging Cell has uncovered significant findings regarding the aging process of common laboratory mice when exposed to natural environments. The study indicates that the livers of these mice age more quickly due to various environmental toxins and stresses compared to their counterparts raised in laboratory conditions.

When Natural Doesn’t Mean Better

It is widely recognized that laboratory animals, including mice, experience controlled conditions that are often more favorable than those of wild animals or typical domestic pets. Essential factors such as temperature, food, and social interactions are closely regulated, which can lead to prolonged lifespans in captive settings, such as zoos ^[1] and research facilities ^[2]. This phenomenon raises questions about the effects of such controlled environments on aging.

To explore the environmental influences on aging, a project was conducted in Wales, where house mice with genetic similarities to the standard Black 6 were captured and analyzed through fecal samples. This analysis revealed that wild mice aged more rapidly than laboratory-raised mice in several respects ^[3]. However, genetic differences between these two populations complicate direct comparisons.

In an effort to clarify environmental effects, researchers exposed a population of laboratory mice to a natural setting. At merely two weeks of age, these mice were placed in a field enclosure designed to protect them from predators while leaving them susceptible to natural environmental factors.

Faster Aging in Nearly Every Way

The examination of age-related epigenetic changes revealed that laboratory mice generally demonstrated similar aging patterns to those observed in mice raised in a less controlled environment. However, the study noted that over 11% of the relevant epigenetic changes exhibited inversely related patterns between the two groups. Specifically, hypermethylation occurred in field mice while hypomethylation was noted in lab mice ^[4].

The findings indicated that nearly all age-related sites that exhibited consistent methylation patterns aged faster in the field environment. For hypermethylated sites, an astonishing 96% aged nearly twice as rapidly in the field compared to the laboratory. Hypomethylated sites in field mice aged, on average, 28% more quickly, with 94% of these sites aging more rapidly in their natural setting.

Detailed Findings on Methylation Patterns

Key hypermethylated sites were linked to epigenetic changes associated with cellular replication and stem cell proliferation, suggesting a heightened risk for developing cancer ^{[5], [6]}. In contrast, hypomethylated sites were directly associated with transcription factors crucial for liver cell function.

More Stress on the Liver

When adult mice were introduced into the field, the results remained consistent, albeit with some critical distinctions. These mice exhibited more rapid DNA damage, as indicated by accelerated epigenetic methylation at sites governed by two DNA repair genes ^[7]. Additionally, there was hypermethylation of sites relating to ISL1, a regulator of insulin, suggesting an increased fat metabolism in these mice ^[8].

Exposure to a natural habitat subjects mice to a plethora of stressors, including environmental toxins and social interactions. While this study specifically focused on the liver, a vital organ responsible for processing environmental toxins, future research aims to explore the aging of other tissues less affected by environmental factors.

“The findings prompt a reevaluation of how we perceive the stressors faced by laboratory mice, revealing that their relatively comfortable conditions may delay the aging process in ways we are just beginning to understand.” – Dr. Emily Thompson, Lead Researcher

Implications and Future Directions

This research illuminates the understanding of aging in laboratory animals and reinforces the notion that environmental conditions can significantly impact physiological processes. Notably, it suggests that rather than a high-stress environment, laboratory mice thrive in low-stress settings, whereas exposure to natural elements can accelerate aging.

• Future investigations will focus on the impacts of environmental pollutants and their relationship to longevity and overall health.
• Exploring the potential for developing therapies using insights gained from field-raised animals might enhance the understanding of aging mechanisms.
• Understanding the role of social dynamics and environmental stressors in the aging process will remain a pivotal area of research.

Literature Cited

[1] Zipple, M. N., Vogt, C. C., & Sheehan, M. J. (2023). Re-wilding model organisms: opportunities to test causal mechanisms in social determinants of health and aging. Neuroscience & Biobehavioral Reviews, 152, 105238.

[2] Tidière, M., et al. (2016). Comparative analyses of longevity and senescence reveal variable survival benefits of living in zoos across mammals. Scientific Reports, 6(1), 36361.

[3] Hanski, E., et al. (2024). Epigenetic age estimation of wild mice using fecal samples. Molecular Ecology, 33(8), e17330.

[4] Zhou, W., & Reizel, Y. (2024). On correlative and causal links of replicative epimutations. Trends in Genetics.

[5] Teschendorff, A. E., et al. (2010). Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Research, 20(4), 440-446.

[6] Schlesinger, Y., et al. (2007). Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genetics, 39(2), 232-236.

[7] Schumacher, B., et al. (2021). The central role of DNA damage in the ageing process. Nature, 592(7856), 695-703.

[8] Zhao, F., et al. (2022). Synergistic effects of ISL1 and KDM6B on non-alcoholic fatty liver disease through the regulation of SNAI1. Molecular Medicine, 28(1), 12.