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SD aged mice

Jiangsu Aniphe BioLab possesses a well-established resource of SD senescent mouse models. Leveraging standardized husbandry and an age‑stratification system, it can provide naturally aged rat models spanning various monthly age stages. These models consistently exhibit age‑related phenotypes, including cognitive decline, heightened oxidative stress, and altered inflammatory profiles, making them suitable for studies on neurodegenerative diseases, anti‑aging research, and the mechanistic investigation of age‑associated disorders. They also support the evaluation of pharmacological interventions and the validation of drug development efforts.

Strain Introduction

SD aged rats are a naturally aging model derived from Sprague-Dawley rats, which are housed under barrier conditions and allowed to age naturally until advanced age (typically 18 months or older). This model faithfully replicates the multiorgan degenerative changes, immune dysfunction, metabolic disturbances, and other hallmarks of normal aging, without requiring genetic modification or pharmacological induction, thereby more closely mimicking the onset and progression of age‑related diseases observed in clinical settings.

SD rats are docile, highly fertile, and well characterized, making them one of the most widely used rodent models of aging in geriatric medicine, pharmacological efficacy evaluation, and nutrition‑intervention research.

Product Advantages

Highly simulates the natural aging process

Without the need for genetic editing, aging is driven naturally by time, characterized by the progressive decline of multi-organ functions. This aligns with the complex, chronic nature of human aging and avoids the phenotypic biases inherent in single-gene models.

Age-related lesions occur simultaneously in multiple systems.

A single animal can spontaneously exhibit a variety of aging phenotypes, including cognitive decline, renal fibrosis, bone loss, immune senescence, and increased tumor susceptibility, making it well suited for research on age‑related comorbidities and geriatric syndromes.

Genetics exhibits population heterogeneity.

Outbred strains maintain rich genetic diversity, and their individual response variability closely mirrors that of human populations, facilitating the analysis of inter‑individual differences in responses to drugs and interventions.

Suitable for long-term chronic intervention studies

Adults maintain a stable body weight range and can tolerate repeated blood draws, drug administration, and the implantation of medical devices—making them an ideal model for research on anti‑aging therapies and nutritional interventions.

The experimental data exhibit a high degree of standardization.

It features a comprehensive reference database encompassing life cycle, behavioral, biochemical, and histopathological data, enabling standardized protocols and facilitating cross‑laboratory data comparison.

Data parameters

Strain Name

SD aged rats (Sprague-Dawley naturally aging model)
Targeted gene

None (natural aging model, non-genetically modified)
Mutation site

None
Types of gene editing

Unedited by genetic engineering
Genetic background

Sprague-Dawley (SD)
Microbial Grade

SPF grade

Validate data

Behavioral Science: Cognitive Decline

Positioning and Navigation Experiment

This figure compares the spatial learning and memory abilities of young and naturally aged rats, as well as those of male and female rats, using a positioning navigation task (A, B) and a spatial exploration task (C–F). Data are presented as mean ± standard error (mean ± SEM), with *p < 0.05 indicating a statistically significant difference compared to the young group.

Compared with young rats, naturally aged rats exhibit marked declines in spatial learning and long-term memory: they take longer to locate the platform during the water maze task and demonstrate reduced learning efficiency; during the probe trial, their memory of the original platform location is impaired, with significantly shorter dwell times in the target quadrant and fewer platform crossings. Moreover, subtle sex differences are observed: female rats generally display lower baseline spatial memory performance than males, and the pattern of age‑related cognitive deficits is similarly pronounced in females.

 

 

New Object Recognition Experiment

This figure uses the Discrimination Index (DI)—which reflects object recognition memory and working memory, with higher values indicating better memory—to compare memory performance among the aged control group (AC), the cognitive-only intervention group (CI), the exercise-only intervention group (EI), and the cognitive–exercise dual-task intervention group (DI). It also examines sex differences by analyzing male and female rats. Data are presented as mean ± standard error (mean ± SEM); *p<0.05 and **p<0.01 versus the AC group.

Natural aging in rats is associated with impaired object recognition memory (with the AC group exhibiting a negative discrimination index); cognitive or motor interventions alone can modestly restore memory, while combined cognitive–motor dual-task training yields the most robust improvements; this protective effect varies by sex, with dual-task training producing statistically significant memory enhancement in female rats, whereas in males only a trend toward improvement is observed.

 

 

Validate data

C57BL/6 normal phenotypic changes

Tumor changes

In aged mice, body weight steadily increases with age, and inter‑individual variability also grows. Typically, after 15 months of age, behaviors such as aggression, excessive grooming, rectal prolapse, cataracts, and spontaneous tumors become more common.

 

Hair changes

Grooming is a social behavior in mice, used to signal one’s rank within the group. Lower-ranking mice, due to frequent grooming, may experience hair loss or bald patches—most commonly on the whiskers and back. Females groom more often than males. As mice age, their coat color becomes progressively darker or lighter, with the appearance of some white hairs and thinning fur; hair loss typically begins near the rump and gradually spreads to the back.

 

Changes in the dorsal fur of mice; image source: Aniphe BioLab.

As shown in the figure above, compared with young mice, aged mice exhibit reduced hair growth length and rate, along with an exceptionally prolonged telogen phase. This inability to re-enter the anagen phase is referred to as “telogen retention.”

The authors of J Invest Dermatol subsequently conducted transplantation experiments to determine whether the skin’s external environment influences hair growth, and then investigated at the molecular level the factors underlying this effect.

 

Transplantation of hair from C57 elderly mice into SCID mice to investigate the effects of the skin microenvironment on hair growth.

 

Experiment on the Effects of Follicle-Inhibiting Protein on Hair Growth in Aged Mice

Through a series of experiments, it has been shown that the thinning of fur in aged mice is due to their hair follicles being trapped in a prolonged “quiescent‑retained” state, preventing them from reentering the growth phase. Meanwhile, the skin microenvironment also plays a critical role in hair growth; analysis revealed that in aged mice, follicle‑inhibiting factors are downregulated, while Wnt pathway inhibitors Dkk1 and Sfrp4 are upregulated—processes that collectively contribute to this phenomenon. We hope these findings will help students and faculty better understand the mechanisms underlying hair growth in aging mice.

Changes in hearing

In old age, hearing (auditory function) gradually declines with advancing age, primarily due to the absence of the Ahl gene, which manifests as disruption of both inner and outer hair cells. Consequently, the auditory‑evoked brainstem response (ABR) threshold is elevated, making it less likely to elicit audiogenic seizures.

 

Comparison of hearing in C57BL/6J mice across different postnatal ages (n=5)

Phenotypic Changes in C57BL/6 Mice

Rectal prolapse

In mice, due to their relatively short rectum, age-related atrophy of the pelvic musculature can make the rectum more prone to prolapse.

Ocular lesions

Relatively speaking, mice have a larger corneal surface area, making them more susceptible to foreign-body exposure and subsequent inflammation. Additionally, with aging, lacrimal gland atrophy and chronic inflammatory conditions can lead to reduced tear production and excessive corneal damage, ultimately resulting in ocular opacity and other pathological manifestations.

Palpable mass

Such subcutaneous or palpable masses within the body may be neoplastic lesions that develop with aging, or they may represent cysts. The most immediate consequence of the formation of an excessively large mass is impaired mobility in mice, which can, in turn, have adverse effects on their overall health.

 

 

Behavioral testing

Cognitive decline, depression, and anxiety-like behavioral changes

Experiments demonstrated that, compared with 2‑month‑old and 12‑month‑old mice, 24‑month‑old mice exhibited varying degrees of impairment in recognition memory, working memory, and spatial memory. In the forced swim test and the tail suspension test, aged mice showed a significantly prolonged immobility time, indicating the emergence of depression‑like behaviors. Both the open‑field test and the elevated plus maze test revealed pronounced anxiety‑like behaviors in aged mice.

 

Changes in Recognition Memory and Working Memory in Aged Rats

 

The Morris Water Maze Test Evaluates Changes in Spatial Memory Across Different Age Groups of Mice

 

Depression-like behavioral changes in aged mice

 

Anxiety-like behavioral changes in mice

Learning ability

Male C57 mice of advanced age typically exhibit higher activity levels and enhanced learning capabilities, making them more suitable than their female counterparts for research in neuroscience, behavioral science, and related fields.

 

 

Scores of C57BL/6 mice of different ages in the nest-building task

 

 

The digging weight of C57BL/6 mice of different ages and sexes

Body weight/survival curve of aged C57BL/6 mice

Survival curve

Many researchers, when conducting studies involving aged mice, often find themselves uncertain about the precise chronological age of these animals. Using human age as a reference, mice can be categorized into three stages—adult, middle-aged, and old—with an overall survival rate of approximately 50%.

01 The 3–6-month-old mouse corresponds to a human aged 20–30 years; at this stage, development is complete and the organism has not yet been affected by aging.

02 In mice, the age range of 10–15 months corresponds to middle age (38–47 years); aging-related changes can be detected for some but not all aging biomarkers.

03 In mice, the age range of 18–24 months corresponds to that of elderly humans (56–69 years); at this stage, nearly all aging‑related biomarkers exhibit detectable changes. According to published data, during the first month after birth, the growth rate of mice is approximately 150 times that of humans; from 1 to 6 months of age, the growth rate of mice is about 45 times that of humans; and after 6 months, the growth rate of mice is roughly 25 times that of humans.

 

 

Survival curve of C57BL/6J mice

Weight change

After 10 months of age, body weight typically increases to over 32 grams (note that mouse strain and diet can also influence body weight). By 15 months, most mice routinely weigh at least 33 grams. At 18 months, aged male mice generally fall within the 32–38 gram range; female mice are usually retired from breeding after eight months, with a minimum weight of 23 grams. Once females reach 18–21 months of age, their body weight is typically 29 grams or more, and by 22 months, most females exceed 30 grams, with some reaching as much as around 40 grams.

 

 

Body weight ranges for female and male rats across age groups

Pathological testing

Increased CD8+ T cells

In the aging brain, there is a marked increase in CD8+ T cells. These cells accumulate with age, damage neurons, and contribute to the decline of cognitive and motor functions. When the number of CD8+ T cells is reduced, or when they fail to become activated or to express cytotoxic effector molecules, the age‑related damage to the brain is significantly attenuated, and the age‑induced impairment of motor function shows partial recovery.

 

 

 

 

Sex Differences in Cell-Specific Neurons of the Hypothalamic Defense System

Fluorescence in situ hybridization was used to label the vesicular glutamate transporter type 2 (Vglut2) and glutamic acid decarboxylase 2 (Gad2), thereby enabling the specific labeling of glutamatergic and γ‑aminobutyric acid (GABA)‑ergic neurons in multiple defense‑related subregions of the hypothalamus.

 

 

In female rats, the absolute number of Vglut2 mRNA‑positive neurons in the AHC was greater than that in the AHP (P<0.05), with a denser Vglut2 mRNA‑positive signal in the ventral region of the AHC adjacent to the caudal end; no statistically significant differences were observed in male rats.

 

 

In mice of both sexes, the DMHv and DMHc predominantly express Gad2 mRNA (P < 0.05). The relative proportion of neurons in the DMHd exhibits sex-specific differences: female mice show higher Gad2 mRNA expression in the DMHd (P < 0.05), whereas in male mice, the expression levels of Vglut2‑ and Gad2‑positive neurons are comparable.

Application areas

● Evaluation of anti‑aging drugs and interventions: Assessing the effects of potential anti‑aging compounds, traditional Chinese medicine extracts, caloric restriction, intermittent fasting, and other interventions on lifespan, healthspan, and aging phenotypes.
● Neurodegenerative disease research: Serves as a natural model for age‑related neurodegeneration, such as Alzheimer’s disease and Parkinson’s disease, and is used for screening cognitive‑protective therapeutics.
● Research on Metabolism and Cardiovascular Aging: Investigates age‑related metabolic and cardiovascular changes, including insulin resistance, dyslipidemia, vascular stiffness, and myocardial fibrosis.
● Research on immune dysfunction: applied to the mechanisms underlying immune aging, diminished vaccine responses, and chronic low-grade inflammation, as well as to the evaluation of immunomodulatory strategies.
● Aging of the musculoskeletal system: Investigating the pathogenesis of sarcopenia and osteoporosis, as well as the efficacy of exercise- and nutrition-based interventions.
● Geriatric oncology: investigates the impact of age on cancer incidence, tumor growth rate, and treatment tolerance.
● Pharmacology and Toxicology: Evaluates the pharmacokinetic and toxicological profiles of drugs in elderly individuals, addressing age‑dependent differences that cannot be captured by young‑adult models.

Breeding Techniques and Precautions

Strictly control inbreeding systems to mitigate genetic divergence.

Environmental Regulation

Aged mice exhibit impaired thermoregulation; maintain a housing temperature of 20–24°C, with a daily temperature range ≤2°C, relative humidity of 40%–70%, and a 12-hour light–dark cycle, while avoiding direct drafts.

Strictly control environmental stimuli to reduce experimental stress.

Bedding cage equipment

Apply a soft bedding layer of at least 2 cm, made from wood shavings or corn cobs; perform localized bedding replacement 1–2 times per week, retaining the old bedding to reduce stress.

Standardize breeding management to improve the survival rate of pups.

Feeding and watering

Feed soft-formulated rodent chow; for older rodents, supplement with softened feed or nutritional gel. Inspect and maintain drinking systems daily, and lower the water bottle height for weaker animals. Continuously monitor changes in food and water intake.

Monitor age-related spontaneous lesions and eliminate experimental confounding.

Health Screening Intervention

Conduct physical examinations at least twice weekly, monitoring fur condition, palpable masses, respiration, anorectal status, dental health, and limb mobility. In the event of sudden weight loss, abdominal distension, or abnormal behavior, perform prompt pathological analysis; for severely ill animals, terminate the experiment early by humane euthanasia.

 

Control male mouse fighting and standardize breeding practices.

Stress Management and Control

Minimize handling, noise, and frequent interventions; employ gentle techniques for drug administration and blood sampling, ensure adequate analgesia during invasive procedures, and extend postoperative monitoring.

Control male mouse fighting and standardize breeding practices.

Cohabitation Guidelines

Keep familiar individuals housed together; avoid co-housing unfamiliar males. If injuries occur or body weight drops sharply, immediately separate the animals and provide appropriate supportive care.

Literature support

Research papers published by Aniphe customers using this model are eligible for SCI-indexed publication. (Original paper link)
J Nutr Biochem 2024 Apr;126:109578
Alginate oligosaccharide alleviates vascular aging by upregulating glutathione peroxidase 7.

Frequently Asked Questions

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Q1: At what age do SD senescent mice begin to be considered elderly?

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A: In experimental studies, SD rats are typically classified as aged at 18 months or older, in the mid-to-late stages of aging between 21 and 24 months, and as very old beyond 24 months. The temporal sequence of aging varies across different tissues and organs; the specific age range should be aligned with the study’s primary endpoint.

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Q2: Which types of research are SD senescent mice best suited for? How should one choose between senescent mice and genetically modified progeria models?

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A: The most suitable models for studying normal physiological aging and age‑related chronic progressive diseases—such as age‑associated cognitive decline, sarcopenia, and metabolic syndrome—are those that closely mimic these conditions. If the goal is to target specific molecular pathways—e.g., telomere dysfunction or DNA repair defects—then corresponding genetically engineered progeroid models are more appropriate. However, when evaluating the ultimate efficacy of anti‑aging therapeutics, the spontaneously aging SD model remains the irreplaceable gold standard.

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Q3: How should persistent weight loss in aged mice be managed?

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A: First, rule out dental issues (such as overgrowth or malocclusion that may interfere with eating), neoplasia (through abdominal palpation and assessment of respiratory status), and infections (including balanoposthitis or pneumonia). Provide soft diets and nutritional gels. If no definitive cause is identified and weight loss exceeds 20% or cachexia develops, euthanasia should be considered from an animal welfare perspective to prevent terminal‑stage suffering.

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Q4: What are the specific requirements for the transportation and acclimatization of SD aged rats?

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A: Transport should be conducted in a transport box lined with soft bedding and provided with an adequate supply of moist feed, while avoiding extreme temperatures. Upon arrival, allow at least 7–10 days for acclimatization before initiating experiments; during this period, monitor body weight and food intake daily. Individuals that continue to exhibit significant weight loss beyond this period should not be included in the study. For aged mice (≥24 months), it is recommended to extend the acclimatization and observation period to 14 days.

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