Name: Frailty Assessment in an Aging Mouse Model (Video) | JoVE Journal
Uploaded: 2025-09-23T14:15:00.000+00:00
Duration: 6 min 58 s
Description: Learn to assess physical frailty in aging C57Bl/6x129J mice using a customizable index without specialized equipment. This protocol enables non-stressful evaluation of age-related functional decline.

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5 minutes

Supported by NIH R01 AG057052

All mice (C57Bl/6x129J) were bred at colonies maintained at the Mayo Clinic. Mice were group housed with littermates by sex, maintained on a 12 h light-dark schedule under specific pathogen-free conditions with ad libitum access to food and water. A convenience sample of mice (n = 46; 36 females) aged 12 to 30 months was evaluated for frailty every 2 weeks for eight months. All protocols and animal care guidelines were approved by the Institutional Animal Care and Use Committee at the Mayo Clinic (protocol A00003349, approved 5 October 2023), in compliance with National Institute of Health Guidelines. Criteria for euthanasia for humane endpoints included weight loss greater than or equal to 20% of body weight, inability to ambulate, inability to reach food and/or water, and tumors including single tumors measuring 2 cm at the longest point of the tumor, multiple tumors with cumulative tumor size (the sum of the longest point of each tumor) equaling 2 cm, or tumor(s) that ulcerate or lose the integrity of the skin covering the tumor for any reason.
1. Setup
NOTE: During the physical frailty assessment, ensure a clean and hazard-free workspace for handling mice and wear proper personal protection equipment.
<ol>
	<li>Collect the necessary equipment-Scale, notebook or laptop for recording data, and a mouse cage.</li>
</ol>
2. Physical frailty assessment
<ol>
	<li>Divide the assessment into three parts-open field examination, manual examination, and weighing. Complete assessments at a consistent location and time of day to minimize anxiety- or ambient-related effect on deficits.
	<ol>
		<li>Open field examination: Transfer the mouse of interest into an open environment and examine several physical characteristics, including the presence of alopecia, loss of fur color, dermatitis, poor coat condition, kyphosis, tail stiffening, gait disorders, tremor, and abnormal breathing.</li>
		<li>Manual examination: Gently scruff the mouse to allow the experimenter to further examine physical characteristics, including the presence of alopecia, loss of fur color, dermatitis, tumors, distended abdomen, cataracts, eye discharge, rectal prolapse, vaginal/uterine/penile prolapse, and poor body condition score. 
		NOTE: Because scruffing is inherently stressful, alternative handling methods such as cupping or tube restraint can be used during transfers and some assessments to minimize animal discomfort and better align with institutional policies.</li>
		<li>Following open field and manual examinations, weigh the mouse. Zero the scale between each animal and record weights to the nearest 0.1 g. Again, ensure time-of-day consistency of the assessment to minimize natural circadian inconsistencies.</li>
	</ol>
	</li>
	<li>Following the assessment of each mouse cage, clean the scale and the open field by spraying surfaces with disinfectant or other appropriate cleaning agent and wiping with a paper towel.</li>
</ol>
3. Examination, including the following 17 characteristics and behaviors
<ol>
	<li>Alopecia-signs of hair loss and/or thinning
	<ol>
		<li>Assess alopecia during both open field and manual examination. Common areas of hair loss and thinning include the back of the neck/upper back, neck and armpits, and stomach. Note that there are natural areas of thinner hair on the underside of mice, especially near joints. Count alopecia only if hair loss and thinning are beyond that of natural patterns observed in young, non-frail mice.</li>
		<li>Score alopecia as follows: 0 = normal fur density; 0.5 &#8804; 25% of body surface displaying fur loss; 1.0 &#8805; 25% of body surface displaying fur loss</li>
	</ol>
	</li>
	<li>Loss of fur color-change in fur color, e.g., from black to grey, brown, or white
	<ol>
		<li>Assess loss of fur color during both open field and manual examination. Changes in fur color often begin on the underside of the mouse but will progress to whole body changes with progressing frailty.</li>
		<li>Score loss of fur color as follows: 0 = normal color; 0.5 = patchy, focal grey, brown, or white changes; 1.0 = grey, brown, or white fur on &#62;25% of body surface</li>
	</ol>
	</li>
	<li>Dermatitis-presence of skin lesions
	<ol>
		<li>Assess dermatitis during both open field and manual examination. Presence of any skin lesions indicating dermatitis, with most focal lesions found on the neck, flanks, and under the chin.</li>
		<li>Score dermatitis as follows: 0 = absent; 0.5 = focal lesions of small size; 1.0 = multifocal or widespread lesions</li>
	</ol>
	</li>
	<li>Coat condition-signs of poor grooming
	<ol>
		<li>Assess coat condition during open field examination. Normal coat condition, usually present in young, non-frail mice, includes a smooth, sleek, shiny coat. Ruffled, matted, and/or ungroomed fur are signs of poor coat condition and often accompany alopecia and changes in fur color.</li>
		<li>Score coat condition as follows: 0 = smooth, sleek, shiny coat; 0.5 = slightly ruffled; 1.0 = unkempt and ungroomed, matted appearance</li>
	</ol>
	</li>
	<li>Kyphosis-presence of curvature of the spine or hunched posture
	<ol>
		<li>Assess kyphosis during the open field examination. Kyphosis is most often present in the upper back and will present as a clear concave curvature beyond that seen in any young, non-frail mice. To confirm the presence of kyphosis, palpate the upper spine to examine for a kyphotic bend. Look for a permanently hunched posture following kyphosis that will be noticeable as a whole-body hunch as opposed to a more local kyphotic bend.</li>
		<li>Score kyphosis as follows: 0 = no cervical to thoracic spinal curvature (approximately 180&#176; to 150&#176;); 0.5 = slight cervical to thoracic spinal curvature (approximately 150&#176; to 130&#176;); 1.0 = significant curvature (&#60;130&#176;) and associated hunched posture</li>
	</ol>
	</li>
	<li>Tail stiffening-lack of curling response to light touch
	<ol>
		<li>Assess tail stiffening during open field examination. While the mouse is freely moving, gently stroke the tail with a finger. The tail of a healthy mouse will wrap around the finger when it is touched. This is best observed when the mouse is relaxed.</li>
		<li>Score tail stiffening as follows: 0 = none; 0.5 = tail responsive but does not curl; 1.0 = tail unresponsive to touch</li>
	</ol>
	</li>
	<li>Gait disorders-abnormalities during locomotion
	<ol>
		<li>Assess the presence of gait disorders during open-field examination. Common changes to the gait include dragging limbs, circling, wobbling, and a wide stance. Use climbing ability to assess gait by placing the mouse on a large cage lid, tilting the lid, and lightly brushing the rear of the mouse to motivate climbing.</li>
		<li>Score gait disorders as follows: 0 = none; 0.5 = abnormal gait but mouse can walk; 1.0 = marked gait abnormality that impairs ability to move freely</li>
	</ol>
	</li>
	<li>Tremor-unprovoked trembling or shaking
	<ol>
		<li>Assess tremor during open-field observation. Monitor the mouse during rest and movement for the presence of a tremor, which usually presents as paw shaking.</li>
		<li>Score tremor as follows: 0 = no tremor; 0.5 = paw shake or tremor during ambulation or high levels of activity; 1.0 = marked tremor with impaired ability to move freely</li>
	</ol>
	</li>
	<li>Breathing rate/depth-abnormal respiratory effort
	<ol>
		<li>Assess breathing rate/depth during open-field examination. Any changes from normal, regular breathing at rest, as observed in a young, non-frail mouse, are scored. Usually, changes include an increased rate and decreased depth of breathing.</li>
		<li>Score breathing rate/depth as follows: 0 = normal; 0.5 = modest change in rate/depth; 1.0 = marked change in rate/depth, or gasping.</li>
	</ol>
	</li>
	<li>Tumors-presence of abnormal masses
	<ol>
		<li>Assess the presence of tumors during manual examination. While scruffing the mouse, examine the mouse for visible tumors and run a finger along the underside of the mouse to check for palpable tumors. Visible asymmetry is a sign of potential tumors. The presence of tumors can be confirmed post mortem if possible.</li>
		<li>Score tumors as follows: 0 = none; 0.5 = one tumor of less than 1 cm3 in volume; 1.0 = single tumor greater than 1 cm3 in volume or multiple smaller tumors</li>
	</ol>
	</li>
	<li>Distended abdomen-presence of excess bulge below the rib cage
	<ol>
		<li>Assess the distended abdomen during manual examination. While scruffing the mouse, assess the presence of excess bulging or abdominal fluid. Look for the presence of a slight bulge below the rib cage to a pronounced W-shaped bulge in the abdomen and palpable during examination.</li>
		<li>Score distended abdomen as follows: 0 = none; 0.5 = slight bulge; 1.0 = clear distension, W-shaped bulge below ribs</li>
	</ol>
	</li>
	<li>Cataracts-presence of cloudy eyes/white spots
	<ol>
		<li>Assess cataracts during manual examination. While scruffed, evaluate the mouse&#39;s eyes for clouding of the cornea. Complete clouding of at least one eye is counted as 1.0.</li>
		<li>Score cataracts as follows: 0 = none; 0.5 = small opaque spot/changes to one or both corneas; 1.0 = significant clouding/spotting of one of both corneas</li>
	</ol>
	</li>
	<li>Eye discharge-buildup of bodily fluid around the eyes
	<ol>
		<li>Assess eye discharge during manual examination. While scruffed, evaluate the mouse&#39;s eyes for evidence of secretions, crusting or discoloration around the edges of the eyes. Discharge is usually dried, associated with swelling, and will result in changes to the normal, sleek, black eye color seen on young, non-frail mice.</li>
		<li>Score eye discharge as follows: 0 = normal; 0.5 = slight swelling of and/or secretions around one or other eyes; 1.0 = significant swelling of and/or secretions around one or both eyes</li>
	</ol>
	</li>
	<li>Rectal prolapse-abnormal extrusion of the rectum
	<ol>
		<li>Assess rectal prolapse during manual examination. While scruffed, examine for signs of prolapsed tissue in the absence of evident straining. Score any rectal tissue prolapsed out of the anus.</li>
		<li>Score rectal prolapse as follows: 0 = no prolapse; 0.5 = some prolapsed tissue, healthy looking; 1.0 = significant prolapsed tissue, unhealthy tissue.</li>
	</ol>
	</li>
	<li>Vaginal/uterine/penile prolapse-abnormal extrusion of genitalia
	<ol>
		<li>Assess vaginal/uterine/penile prolapse during manual examination. While scruffed, examine for signs of prolapsed tissue in the absence of evident straining. Score any genitalia prolapse.</li>
		<li>Score vaginal/uterine/penile prolapse as follows: 0 = no prolapse; 0.5 some prolapsed tissue, healthy looking; 1.0 = significant prolapsed tissue, unhealthy tissue. 
		NOTE: Prolapse can occur due to distress from handling, so if a deficit is suspected, place the mouse back onto the open field, lifting the tail to confirm the presence of prolapsed tissue.</li>
	</ol>
	</li>
	<li>Body condition score-presence of excess or minimal fat and evidence of loss of muscle mass
	<ol>
		<li>Assess body condition score during manual examination. While scruffing the mouse, take note of the amount of fat covering the lower back and pubic bone; frailty will usually present a loss of fat in this region. Moderate loss of fat resulting in more prominent bones than young, non-frail mice will be scored as 0.5. Once the bones become very prominent, even sharp, or there is evident loss of muscle mass, the score will be 1.0.</li>
		<li>Score body condition score as follows: 0 = bones palpable but not prominent; 0.5 = bones prominent and/or barely felt; 1.0 = bones very prominent and/or not felt.</li>
	</ol>
	</li>
	<li>Weight-assessment at a consistent time of day (e.g., within 2 to 4 h of the beginning of the inactive period) following the open-field and manual examination.
	<ol>
		<li>Assess weight following frailty measures.</li>
	</ol>
	</li>
</ol>
4. Implementing the physical frailty assessment
NOTE: Much of the implementation of this assessment should be customized to the needs of the experimenter and their experimental goals. Details provided here can serve as an example of how one might implement the frailty assessment and provide some helpful guidance for general purposes.
<ol>
	<li>Frequency: Once a cohort or colony of mice to be assessed is identified, make physical frailty assessments every 2 weeks. Keep the time and day of the assessments consistent during the evaluation period.</li>
	<li>Data Recording: During the evaluation of each mouse, assess a score (0, 0.5, or 1.0) to each of the frailty measures and record a weight; use an average of the scores of all sixteen deficits is used as a final frailty score. Take any relevant notes regarding the health and behavior of the mice, including changes to any of the measures that will require increased attention during subsequent evaluations and abnormal posthandling behaviors. Perform no rescoring for prior scores. Compute the frailty index as the arithmetic mean of the 16 deficit scores (0/0.5/1.0), expressly excluding body weight from the calculation. 
	NOTE: It is vital to ensure the correct data is being ascribed to the correct mouse over the course of the longitudinal evaluation period.</li>
</ol>

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<li>Abellan Van Kan, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+i.A.N.A+task+force+on+frailty+assessment+of+older+people+in+clinical+practice%5BTitle%5D)+AND+%22J+Nutr+Health+Aging%22%5BJournal%5D)">The i.A.N.A task force on frailty assessment of older people in clinical practice.</a> J Nutr Health Aging. 12 (1), 29-37 (2008).</li>
<li>Abellan Van Kan, G., Rolland, Y. M., Morley, J. E., Vellas, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Frailty%3A+Toward+a+clinical+definition%5BTitle%5D)+AND+%22J+Am+Med+Dir+Assoc%22%5BJournal%5D)">Frailty: Toward a clinical definition.</a> J Am Med Dir Assoc. 9 (2), 71-72 (2008).</li>
<li>Roh, E., Choi, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Health+consequences+of+sarcopenic+obesity%3A+A+narrative+review%5BTitle%5D)+AND+%22Front+Endocrinol+%28Lausanne%29%22%5BJournal%5D)">Health consequences of sarcopenic obesity: A narrative review.</a> Front Endocrinol (Lausanne). 11, 332(2020).</li>
<li>Brooks, S. P., Dunnett, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Tests+to+assess+motor+phenotype+in+mice%3A+A+user%27s+guide%5BTitle%5D)+AND+%22Nat+Rev+Neurosci%22%5BJournal%5D)">Tests to assess motor phenotype in mice: A user's guide.</a> Nat Rev Neurosci. 10 (7), 519-529 (2009).</li>
<li>Fahlstrom, A., Yu, Q., Ulfhake, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Behavioral+changes+in+aging+female+c57bl%2F6+mice%5BTitle%5D)+AND+%22Neurobiol+Aging%22%5BJournal%5D)">Behavioral changes in aging female c57bl/6 mice.</a> Neurobiol Aging. 32 (10), 1868-1880 (2011).</li>
</ol>

All authors have no conflicts of interest to declare.

Critical to the success of this frailty index is consistency when evaluating the many subjective criteria that may be present with deficits. Several steps can be taken to ensure the quality of results and overall reliability of this index. The same investigator can be used during observation, ensuring that the same judgement of deficit score will be given across animals and time points. If experiment design or logistics prevent this consistency, each investigator should independently familiarize themselves with the index...

Frailty comprises increased susceptibility to adverse health outcomes typically associated with advanced age1,2,3. It presents as decreased resilience to stressors and loss of normal physiological function, potentially limiting independence and predisposing older individuals to co-morbidities and mortality3,4,5. Frailty may help explain the differences in health outcomes commonly seen between those of the same chronological age6. In humans, frailty assessments include the frailty phenotype7,8and the frailty index9,10,11, which assess physical performance (e.g., weakness, endurance, or weight loss) and the number of deficits across organ systems, respectively. Animal studies have incorporated a five-physical-criterion frailty score as well as a 31 item frailty index12,13,14. Both approaches have their strengths and weaknesses. Frailty phenotyping allows excellent characterization of decreased physical performance, of value for projects interested in sarcopenia, neuromotor dysfunction, or any other aging-related change in physical function. Phenotyping is non-invasive and non-terminal. However, this method of quantifying frailty requires specialized equipment (e.g., rodent treadmills, rotarods, running wheels, and grip meters) and is very time-consuming. A frailty phenotype focusing on physical function lacks the robustness of indices that consider frailty across various body systems. Accordingly, frailty indices developed to assess deficits across multiple systems create a more comprehensive rating of frailty. They are also generally non-invasive, easy to administer, and do not require specialized equipment or extensive time. Frailty indices based on deficit accumulation do not readily assess cognitive function and introduce subjectivity in scoring deficits, particularly if multiple evaluators are used, though the effects of this subjectivity can be minimized through discussing and refining assessment techniques15.
The goal of the present method is to quantify frailty using a simple, practical tool, allowing for frailty to be added as a longitudinal outcome to existing and future projects. Multiple considerations were made when developing a frailty measure to fit this goal, one being the reliance on specialized equipment. Several frailty phenotyping methods have been proposed but they require equipment that may be inaccessible to some or impractical for frequent use. For example, open-field monitoring is used in some frailty phenotyping studies to measure exploratory behaviors and voluntary physical activity16,17. Phenotyping by open-field monitoring requires both specialized camera and computer equipment and considerable time commitment as the mice individually undergo the acclimation and observation periods. Other phenotypes require the use of specialized equipment like rodent treadmills and Rotarods13,18,19. The demands that a suite of tests, including these and other measures, places on animal subjects are too great for the frequent, repeated tests needed in a longitudinal study design, not to mention the animal acclimation and investigator training required for each. So, while not aligned with our goal, frailty phenotyping and the common tests used can be applicable to experiments requiring cross-sectional and infrequent longitudinal observation.
Frailty indices are generally non-invasive, are practical to integrate into projects, and can be time efficient12,20. Using an index also allows for details to be drawn from existing methodologies that have been shown to be reproducible and reliable15,21. In collaboration with multiple veterinary staff with experience assessing mouse frailty, an abbreviated list of criteria/deficits was selected from a larger list12, including criteria of the integument (alopecia, loss of fur color, dermatitis, coat condition), musculoskeletal (kyphosis, tail stiffening, tumors, distended abdomen, body condition score), neuromuscular (gait disorders, tremor), sensory (cataracts, eye discharge/swelling), urogenital (rectal and vaginal/penile prolapse), and respiratory (breathing rate/depth) systems. These deficits were chosen specifically as they cover a comprehensive range of systems and can be evaluated without equipment or specialized examinations beyond open-field and manual examination. The specific list these are drawn from has been clinically validated12 and confirmed to have high inter-rater reliability as found by multiple laboratory groups15,21. This was an important consideration given the subjective nature of many of the chosen deficits. Reasons for deficits to be excluded from the abbreviated index included requirement of some form of equipment (grip strength, temperature) specialization beyond the desired scope of this simple index (loss of whiskers, vestibular disturbance, corneal opacity, vision and hearing loss, microphthalmia, nasal discharge, piloerection), and avoidance of institutional humane endpoints (diarrhea, malocclusions, mouse grimace scale). The present tool, therefore, represents a pragmatic subset of the validated 31 item index, tailored to minimize equipment needs and time burden while maintaining multi-system coverage. It is important to note that the present protocol describes one such way a larger frailty index can be adapted to fit the goals of a given experiment, serving as a guide for investigators interested in simplified or customized tools for assessing mouse frailty. Body weight was also included in the assessment, but not in the estimation of the frailty index, as conflicting reports suggest variable impact of both weight gain and loss on frailty12,14,22,23. The purpose of shortening the list of deficits used in determining the frailty index was to highlight the flexibility and adaptability of such an index while simplifying the measurement tool to the selected criteria and retaining the comprehensive assessment of frailty in C57Bl/6x129J mice. This change allows for a complete assessment of frailty without equipment-intensive methods or complicated examination. With some training, investigators can expect this comprehensive assessment of physical frailty to take less than 2 min for a single mouse compared to nearly 4 min for a longer, 31 item index12.

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frailty assessment in an aging mouse model

Frailty Assessment in an Aging Mouse Model

A frailty index (FI) is a powerful method of assessing animal models of aging, serving as a proxy measure of biologic age and health span. Frailty represents a state of increased vulnerability to adverse outcomes due to the accumulation of health deficits that limit independence. The concept is valuable for animal studies that inform human geroscience. For example, using FI scores, animals with a similar chronological age can be differentiated by their biological age. Thus, FI can be used in preclinical studies to measure biological age, track frailty longitudinally, and assess health span.
A murine frailty index was recently developed using 31 health-related deficits. However, its length and requirement for specialized equipment pose limitations in practical use. Here, we present an adapted 16 item frailty index that excludes parameters requiring special instrumentation or invasive testing. The selected deficits are easily observable or measurable and evaluate integument, musculoskeletal, neuromuscular, sensory, urogenital, and respiratory systems. Body weight is measured for longitudinal tracking but excluded from the FI calculation. Each deficit is scored as 0, 0.5, or 1, based on severity, with the FI computed as the mean of the 16 deficit scores.
This streamlined FI allows rapid assessment of large cohorts, can be applied longitudinally to the same animals, and requires no specialized equipment. We demonstrate its feasibility in C57BL/6&#215;129 mice, showing age-associated increases in frailty, variation among individual mice, and the ability to detect deficits across multiple systems. This tool enables laboratories to incorporate frailty into diverse experimental designs, provides a practical approach for assessing health span, and enhances translational relevance in geroscience. This frailty index is adapted from previously validated mouse clinical frailty methodologies and is intended for straightforward, longitudinal use alongside ongoing studies.

A convenience sample of naturally aging C57Bl/6x129J mice was assessed for frailty using the index described here. Each mouse (n = 46; 36 females) over 12 months of age was assessed every 2 weeks, with the evaluation period lasting approximately 6 months. A cross-sectional cohort at four ages of interest (12, 18, 24, and 30 months) was selected to assess frailty index scoring across age groups representing 100%, 95%, 80% and 30% survival, respectively24. T...

The goal of the present protocol is to provide instructions and guidelines for assessing physical frailty in C57Bl/6x129J laboratory mice. Specific details regarding each measure used in the physical frailty index are explained. Several methods for reporting frailty results are also presented.

A frailty index (FI) is a powerful method of assessing animal models of aging, serving as a proxy measure of biologic age and health span. Frailty ...

Aging involves progressive loss of normal functions and differs across individuals. Frailty reflects the inability to maintain function with stressors. Studying frailty can enhance understanding of aging variability and progression.Despite the frequent use of frailty assessments clinically, many preclinical aging projects don't include frailty as a variable of interest, potentially because of obstacles to implementing a frailty assessment tool. This frailty index requires no specialized equipment or stressful testing for mice. It is customizable, allowing investigators to tailor assessments to specific dimensions of frailty relevant to their research focus.We hope that presenting the feasibility of simplifying and implementing a frailty index will encourage others to use frailty as a variable of interest, making for more clinically relevant projects. To begin, divide the assessment into open-field examination, manual examination, and weighing. For the open-field examination, transfer the mouse of interest into an open environment.Examine physical characteristics including alopecia, loss of fur color, dermatitis, poor coat condition, kyphosis, tail stiffening, gait disorders, tremor, and abnormal breathing. For the manual examination, gently scruff the mouse. Examine for alopecia, loss of fur color, dermatitis, tumors, distended abdomen, cataracts, eye discharge, rectal prolapse, vaginal or penile prolapse, and poor body condition score.Assess weight following open-field and manual examinations at a consistent time of day within two to four hours of the beginning of the inactive period. During open-field examination, assess for gait disorders. Dragging limbs, circling, wobbling, or a wide stance are signs of gait disorders.To further evaluate gait disorders, place the mouse on a large-cage lid and tilt it. Lightly brush the mouse's rear to encourage climbing. Next, allow the mouse to acclimatize, and observe the mouse at rest for changes to breathing rate and depth.Gently stroke the tail with a finger to assess tail stiffness. During the open-field examination, assess integumentary criteria including alopecia, loss of fur color, dermatitis, and poor coat condition. Alopecia is commonly present on the back of the neck and will be visible as the mouse moves freely.Kyphosis is best assessed by observing the mouse's spinal curvature during the open-field examination, both at rest and while moving. Kyphosis is scored based on the extent of abnormal curvature of the spine visible during movement and hunched posture at rest. Manually examine by scruffing the mouse.Use fingers to assess the extent of fat and muscle loss around the pubic bone and lower spine, which are used to evaluate body condition score. While holding the mouse, examine the eyes for signs of eye discharge, crusting, or discoloration, and for cataracts. Observe the thoracic and abdominal areas for additional signs of alopecia, which occur commonly around joints, change in fur, color, and dermatitis.Gently rub a finger along the abdomen to assess for the presence of tumors or distended abdomen. Carefully tilt the mouse head down to assess for the presence of rectal and vaginal or penile prolapse. If there is suspected prolapse, gently lower the mouse to the open-field area.Once it has returned to rest, gently lift the tail to confirm prolapse in the absence of any strain caused by handling. Following the open-field and manual examinations, weigh the mouse. Zero the scale between each animal, and record the weight to the nearest 0.1 gram.During evaluation of each mouse, assign a score of 0, 0.5, or 1.0 to each frailty measure. Record the weight and calculate the average of all 16 measures to generate a final frailty score. Take notes on any health or behavioral changes requiring follow-up, as well as any abnormal post-handling behaviors.Frailty index values increased progressively with age across all measured groups at 12, 18, 24, and 30 months. At 18 months, alopecia, kyphosis, and loss of fur color were the most frequently observed deficits, particularly in male mice. At 24 months, body condition score and poor coat condition deficits became common.Longitudinal data showed that frailty rose with age for both sexes, with male mice having higher frailty values at similar ages. Very few males were observed beyond 120 weeks of age, indicating reduced survival in males. Mice that experienced more than 10%body weight loss were of advanced age and had frailty index values exceeding 0.15.Most mice had minimal frailty index changes of less than 0.05 over two-week intervals. Larger frailty increases were more frequent at older ages and accompanied by notable weight loss. Four phenotypes of frailty weight change were observed, with the most common being frailty increase without weight change, present in 46%of tracked animals.30%exhibited no change in either frailty or weight. 12%of mice showed either frailty increase with weight gain or frailty increase with weight loss.

frailty-assessment-in-an-aging-mouse-model

Research

JoVE Journal

Biology

The primary outcome measure in clinical trials for neuromuscular disorders is generally improved muscle function. Therefore, assessing the effect of potential therapeutic compounds on muscle performance pre clinically in mouse models is of great importance. We here describe several functional tests to address this.

Assessing Functional Performance in the Mdx Mouse Model

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Behavioral Assessment of the Aging Mouse Vestibular System

A reverse-genetics approach to understanding gene families associated with human disease is presented, using mouse as a model system, and the subsequent mouse phenotyping schedule is described. Because mice defective in a gene of interest, HtrA2, manifested Parkinsonian symptoms, the phenotyping regimen is focused on identifying neurological defects.

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A Mouse Model of Fatigue Induced by Peripheral Irradiation

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A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

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Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice

The social threat-safety test allows a simultaneous assessment of social avoidance development as a measurement of aversive conditioned learning and social threat-safety discrimination ability, both utilized to identify stress-susceptible and stress-resilient individuals within a single group of chronically socially defeated male mice.

Social Threat-Safety Test Uncovers Psychosocial Stress-Related Phenotypes

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Genetic Studies of Human DNA Repair Proteins Using Yeast as a Model System 

Learn to assess physical frailty in aging C57Bl/6x129J mice using a customizable index without specialized equipment. This protocol enables non-stressful evaluation of age-related functional decline.

Frailty Assessment in an Aging Mouse Model

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