When are mice considered old?

Mice are widely used models for both aging and senescence because of their similarity to humans. These two terms, though often used interchangeably, are not the same. Aging refers to biological change with time across the lifespan, which also includes developmental milestones in childhood and adolescence; however, senescence refers to normal progressive impairments in function that occur with age. Age-related disease refers to health conditions for which the incidence increases with age, such as cancer, heart disease, arthritis, osteoporosis, and cognitive decline. Many of these conditions are modelled in mice, prompting questions about how the life history of mice correlates with humans.

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The figure below compares the life phases and maturational rates of mice and humans superimposed on a survival curve based on a large cohort of C57BL/6J mice (150 males and 150 females). The maturational rate of mice does not linearly correlate with humans—it occurs 150 times faster during the first month of life and 45 times faster over the next five months, during which mice pass through their mature adult stage. Mature adult mice range in age from 3 – 6 months; the life phase equivalent for humans ranges from 20 – 30 years.

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Figure. Life history stages in C57BL/6J mice in comparison to human beings. Data Adapted from Figure 20-3: Flurkey, Currer, and Harrison, 2007. “The mouse in biomedical research” in James G. Fox (ed.), American College of Laboratory Animal Medicine series (Elsevier, AP: Amsterdam; Boston). Additional related information can be found in the Harrison Laboratory’s online article Life Span as a Biomarker.

Because this group is past development but not yet affected by senescence, the mature adult group is often used as the reference group for any age change in aging studies. Mice in such a control group should be at least three months old because, although sexual maturity is reached around 35 days of age, rapid growth continues until about three months.

After 6 months of age, the maturational rate of mice is 25 times faster than humans. A feature of middle age is the presence of senescent changes in some, but not all, biological measures that will eventually change with age (e.g., biomarkers of aging). A middle-aged group can help determine if an age-related change is progressive or is first expressed only in old age. Mice should be at least 10 months old for inclusion in a middle age group and the upper age limit is about 14 – 15 months. This phase correlates to humans from 38 – 47 years old.

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Mice ranging from 18 – 24 months of age correlate with humans ranging from 56 – 69 years of age. This age range meets the definition of “old,” which is the presence of senescent changes in almost all biomarkers in all animals. For C57BL/6J mice, the upper limit for this group is ~24 months, when the onset of strain-specific diseases can affect biomarkers and produce misleading results. With advanced age, necropsies and pathologic assessment become essential for accurate interpretation of data. Many of the histological lesions associated with aging are quite apparent by 24 months. Mice over 24 months of age can be considered “very old” and survivorship drops off markedly.

JAX provides study-ready aged C57BL/B6 males and females between 25 and 78 weeks of age. These mice are managed by our patented Genetic Stability Program to minimize genetic drift within the colony. Visit the Aged C57BL/B6 page to learn more.

References:

Harrison Laboratory’s online article Life Span as a Biomarker

Flurkey, Currer, and Harrison, 2007. ‘The mouse in biomedical research.’ in James G. Fox (ed.), American College of Laboratory Animal Medicine series (Elsevier, AP: Amsterdam; Boston).