SAMR1 Strain Research Articles

Optical development in the murine eye lens of accelerated senescence-prone SAMP8 and senescence-resistant SAMR1 strains

The eye lens is responsible for focusing objects at various distances onto the retina and its refractive power is determined by its surface curvature as well as its internal gradient refractive index (GRIN). The lens continues to grow with age resulting in changes to the shape and to the GRIN profile. The present study aims to investigate how the ageing process may influence lens optical development. Murine lenses of accelerated senescence-prone strain (SAMP8) aged from 4 to 50 weeks; senescence-resistant strain (SAMR1) aged from 5 to 52 weeks as well as AKR strain (served as control) aged from 6 to 70 weeks were measured using the X-ray interferometer at the SPring-8 synchrotron Japan within three consecutive years from 2020 to 2022. Three dimensional distributions of the lens GRIN were reconstructed using the measured data and the lens shapes were determined using image segmentation in MatLab. Variations in the parameters describing the lens shape and the GRIN profile with age were compared amongst three mouse strains. With advancing age, both the lens anterior and posterior surface flattens and the lens sagittal thickness increase in all three mouse strains (Anterior radius of curvature increase at 0.008 mm/week, 0.007 mm/week and 0.002 mm/week while posterior radius of curvature increase at 0.002 mm/week, 0.007 mm/week and 0.003 mm/week respectively in AKR, SAMP8 and SAMR1 lenses). Compared with the AKR strain, the SAMP8 samples demonstrate a higher rate of increase in the posterior curvature radius (0.007 mm/week) and the thickness (0.015 mm/week), whilst the SAMR1 samples show slower increases in the anterior curvature radius (0.002 mm/week) and its thickness (0.013 mm/week). There are similar age-related trends in GRIN shape in the radial direction (in all three types of murine lenses nr2 and nr6 increase with age while nr4 decrease with age consistently) but not in the axial direction amongst three mouse strains (nz1 of AKR lens decrease while of SAMP8 and SAMR1 increase with age; nz2 of all three models increase with age; nz3 of AKR lens increase while of SAMP8 and SAMR1 decrease with age). The ageing process can influence the speed of lens shape change and affect the GRIN profile mainly in the axial direction, contributing to an accelerated decline rate of the optical power in the senescence-prone strain (3.5 D/week compared to 2.3 D/week in the AKR control model) but a retardatory decrease in the senescence-resistant strain (2.1 D/week compared to the 2.3D/week in the AKR control model).

Bone marrow stromal cells from low-turnover osteoporotic mouse model are less sensitive to the osteogenic effects of fluvastatin.

This study aimed to investigate the effects of fluvastatin on the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts in senescence-accelerated mouse prone 6 (SAMP6) compared with that in the normal senescence-accelerated-resistant mouse (SAMR1) model. SAMP strains arose spontaneously from the AKR/J background and display shortened life span and an array of signs of accelerated aging, compared with control SAMR strains. The dose effects of fluvastatin were also evaluated. BMSCs were cultured with/without fluvastatin (0 μM, 0.1 μM, 0.5 μM, and 1.0 μM). WST-1-based colorimetry was performed to evaluate cell proliferation. To evaluate cell differentiation, gene expression levels of bmp2 and runx2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and protein expression levels were determined using enzyme-linked immunosorbent assay (BMP2) and immunofluorescence staining (BMP2 and Runx2). Alkaline phosphatase (ALP) activity assay and histochemical detection were determined; the effect of noggin, a BMP-specific antagonist, was examined using ALP histochemical detection. To assess for mature osteogenic marker, gene expression levels of bglap2 were determined by qRT-PCR and mineralization was determined by alizarin red staining. RhoA activity was also examined by Western blotting. In SAMP6, BMP2, Runx2 and Bglap2 mRNA and protein expressions were significantly increased by fluvastatin, and ALP activity was increased by BMP2 action. RhoA activity was also inhibited by fluvastatin. The concentration of fluvastatin sufficient to increase BMP2 and Runx2 expression and ALP activity was 0.5 μM in SAMP6 and 0.1 μM in SAMR1. In conclusion, the present study revealed that fluvastatin promoted BMSC differentiation into osteoblasts by RhoA-BMP2 pathway in SAMP6. BMSCs of SAMP6 are less sensitive to the osteogenic effects of fluvastatin than SAMR1.

Assessment of social interaction and anxiety-like behavior in senescence-accelerated-prone and -resistant mice

Two members of the senescence-accelerated mouse group, SAMP8 and SAMP10, are characterized by learning and memory deficits, while the SAMR1 strain is not. In this study, we used two behavioral tests, social approach and object recognition and compared the results observed for the SAMP strains with those seen in the control strain, SAMR1. In social approach experiments, the 2 SAMP strains showed decreased sociability compared to SAMR1 as shown by their reluctance to spend time near a stranger mouse and increased immobility. In object recognition experiments, SAMP strains spent more time in the thigmotaxis zone and less time in the more exposed central zone than SAMR1 mice. From a behavioral standpoint, SAMP mice were less interactive and showed increased anxiety-like behavior compared to SAMR1.

Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice

Adipose tissue provides for a rich and easily accessible source of multipotent stromal cells and thus offers the potential for autologous cell-based therapy for a number of degenerative diseases. Senile osteoporosis is characterized by a reduction in bone quality, which is associated with inadequacies in bone marrow stromal cell (BMSC) differentiation. In the present study, we have characterized adipose-derived stromal cells (ASCs) isolated from aged osteoporotic mice and evaluated their suitability as a source of osteogenic precursor cells. Significant reductions in both tibia bone quality and telomere length in liver tissue were observed in the senescence-accelerated mouse prone 6 strain (SAMP6), as compared to the control age-matched senescence-accelerated mouse resistant 1 strain (SAMR1), thus confirming osteoporosis and accelerated ageing traits in this model. ASCs isolated from inguinal fat expressed mesenchymal surface markers and were capable of differentiating along the osteoblast, adipocyte and chondrocyte lineages. Telomere length was not compromised in ASCs from SAMP6 mice but was actually found to be significantly increased as compared to control SAMR1 mice. Furthermore, ASCs from both strains were comparable in terms of telomerase activity, p21 mRNA expression, SA-β-gal activity and proliferative capacity. The overall osteogenic and adipogenic potential of ASCs was comparable between SAMP6 and SAMR1 strains, as determined by quantitative molecular, biochemical and histological analyses. In conclusion, adipose tissue may represent a promising autologous cell source for the development of novel bone regenerative therapeutic strategies in the treatment of age-related osteoporosis.

American ginseng improves neurocognitive function in senescence‐accelerated mice: Possible role of the upregulated insulin and choline acetyltransferase gene expression

To investigate the effects of American ginseng on neurocognitive function and glucose regulation in senescence-accelerated mice. Male senescence-resistant inbred strains (SAMR1) and senescence-prone inbred strains (SAMP10) mice were divided into five groups and fed either a control diet or an American ginseng-supplemented diet (1% or 2% g/g) from 6 weeks to 10 months of age. Bodyweight, levels of fasting plasma glucose (FPG) and grading scores were monitored every month and neurocognitive functions were evaluated at 9 months of age with a KUROBOX apparatus using a stress-free positive cue task. Gene expressions of peroxisome proliferator-activated receptor delta (PPAR-δ), insulin, choline acetyltransferase (ChAT) and amyloid precursor protein (APP) in the brain were measured by real-time quantitative reverse transcription polymerase chain reaction assays. American ginseng decreased FPG in SAMR1 mice, but increased FPG in SAMP10 mice. Correct visit ratios were higher in both SAMR1 and SAMP10 strains consuming an American ginseng-supplemented diet. Gene upregulation of insulin and ChAT in the brain, but not of PPAR-δ or APP, was evident in American ginseng-fed groups. Daily consumption of American ginseng induced an enhancement in neurocognitive function in senescence-accelerated mice, which could be related to the upregulation of insulin and ChAT gene expression in the brain. Geriatr Gerontol Int 2012; 12: 123-130.

Senescence‐accelerated Mouse Displays Aberrant Bone Metal Composition

Senescence-accelerated mouse (SAM) is a genetically controlled mouse strain which has been used as a murine model of accelerated senescence, including osteoporosis, and aging-related neural disorders. To analyse the pathogenic changes in bone during senescence, we have measured bone metal composition in normal mice and SAM mouse. SAM-P/6 mice showed significant changes in zinc (21% increase) and silicon (43% decrease) compared with the control senescence-resistant mouse (SAM-R/1). The average measured values were: Zn 147 μg g−1; Fe 100 μg g−1; Ca 73 mg g−1; S 2.0 mg g−1; P 93 mg g−1; Si 531 μg g−1; Mg 2.8 mg g−1; Na 731 μg g−1 for the SAM-R1 strain, and Zn 179 μg g−1; Fe 105 μg g−1; Ca 80 mg g−1; S 2.1 mg g−1; P 95 mg g−1; Si 299 μg g−1; Mg 3.0 mg g−1; Na 750 μg g−1 for the SAM-P/6 strain. Calcium phosphate is a major form of calcium stock in bones, but neither Ca nor P displayed marked changes between the two strains. Likewise, both strains had similar amounts of other elements (Fe, S and Na). At present, it is unclear whether the increase of zinc in the SAM-P/6 mouse is a result of an aberrant biochemical process or is causative of the modification of activities of crucial proteins, enzymes for bone metabolism. It also is not yet clear whether the accumulation of silicon is a primary event during bone-related pathogenesis in SAM-P/6 mice.

Early Amyloid Accumulation in the Hippocampus of SAMP8 Mice

Late-onset Alzheimer's disease (AD) is the most common form of AD appearing after 65 years of age. To date, however, there are no non-genetically manipulated rodent models that develop a similar sporadic onset of AD with age-related amyloid-beta (Abeta) deposition. Although the senescence accelerated mouse prone 8 (SAMP8) mice have been proposed as a model of AD, the presence of Abeta deposits remains controversial. In this study, we describe the time course of Abeta deposition in SAMP8 mice as well as in control SAMR1 and ICR-CD1 strains of mice. From as early as 6 months onward, SAMP8 mice show Abeta deposition in the hippocampus that increase in number and extent with age. These deposits are comprised of by clustered granules that contain Abeta{42}, Abeta{40}, and other Abeta protein precursor fragments. By marked contrast, control mice show only low numbers of Abeta clusters that do not develop until 15 months of age. The demonstration that SAMP8 mice present with amyloid deposits in their hippocampus makes this animal model a useful tool to understand the mechanisms involved in Abeta deposition in AD.

노화촉진마우스의 텔로미어 함량 분석

Telomeres, comprised of tandem repeats of TTAGGG sequences, are special nucleoprotein structures that protect and stabilize chromosome ends. These structures form the crux of the telomere concept of aging, senescence and genomic instability. The classic terminal restriction fragment (TRF) analysis to quantify the amount of telomeric DNA is disadvantageous in species containing ultra long telomeres like in mice (100Kb). In this study, we used a more sensitive quantitative fluorescence in situ hybridization (Q FISH) technique to quantify telomeric DNA, and used it as a biological aging marker in mice. 12 litters each of Senescence-Resistant (SAMR1) and -Prone (SAMP1) known as senescence accelerated mouse strains were purchased from Central Lab, Animal Inc. We quantified the amount of telomeric DNA using telomere specific DNA probes on the two strains of male mice at 8 weeks, 18 weeks and 26 weeks of age. The amount of telomeric DNA correlated with aging and age associated changes in body and organ weight between SAMR1 and SAMP1 strains of mice. These data suggest the usefulness of the amount of telomeric DNA as a biological aging marker in human aging studies.

Age-related expression of adenosine receptors in brain from the senescence-accelerated mouse

Senescence-accelerated mice (SAM) are used as a model of aging and age-associated diseases. SAMP8 are prone strains that show shortened life span and deficits in learning and memory processes, while SAMR1 are strains of accelerated senescence-resistant, long-lived mice. Due to their abnormal APP (amyloid precursor protein) metabolism in brain, SAMP8 may be an Alzheimer-type model. Adenosine receptors are G-protein coupled receptors which are altered in brain from Alzheimer disease (AD) cases. The analysis of adenosine receptors in brain from young (21 days old) and middle-aged (180 days old) SAMP8 as compared with SAMR1 mice revealed differences between these strains associated with age. The age-related increase in mRNA coding A 1 and A 2B receptors observed in SAMR1 was absent in SAMP8. A 1 receptors were significantly decreased with age in SAMR1, while no differences were observed in SAMP8. However, the levels of A 1 receptors in young SAMP8 were even lower than those obtained in middle-aged SAMR1. In addition, A 2A receptors were significantly increased only in aged SAMR1. A similar age-related decrease in A 1 receptors level was also observed in brain from male Wistar rats. These results suggest different age-related effects on adenosine receptors in SAMR1 and SAMP8 strains. Since A 1 receptors are mainly neuroprotective, their important loss in very young SAMP8 strain suggests the involvement of these receptors in the pathogenesis of neurodegenerative diseases associated with aging.

The Senescence-accelerated Mouse (SAM): A Higher Oxidative Stress and Age-dependent Degenerative Diseases Model

The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions.

Age-related difference in nociceptive behavior between SAMP6 and SAMR1 strains

Senescence accelerated prone mouse 6 (SAMP6) mice have been known to be a model for accelerated aging. Compared with the normal control senescence accelerated resistant mouse 1 (SAMR1) mice, although the SAMP6 mice have normal bone mass at 4 months, they exhibit a significantly lower bone mass at 8 months. It was recently reported that SAMP6 has memory deficit at 4 months of age, indicating that the change of nervous function might be already detected at 4 months of age. To assess whether SAMP6 mice exhibit an age-related abnormality of nociceptive transmission, we examined a battery of tests using the von Frey test for mechanically induced response, the hot plate test for thermally induced response, and the formalin paw test for chemically induced response. SAMP6 and SAMR1 showed similar response patterns in the von Frey test and the hot plate test. In the formalin paw test, 1-month-old SAMP6 and SAMR1 had similar responses, while 4-month-old SAMP6 exhibited attenuated phase 2 response, but normal phase 1 response. These findings indicate that onset of age-related phenotypes in SAMP6 differs in different tissues. SAMP6 could be useful to delineate the involvement of age-related nociceptive mechanisms.

Lithium Treatment Decreases Activities of Tau Kinases in a Murine Model of Senescence

Lithium modulates glycogen synthase kinase 3beta (GSK-3beta), a kinase involved in Alzheimer disease-related tau pathology. To investigate mechanisms of aging and the potential therapy of lithium in neurodegenerative disease, we treated senescence-accelerated mouse (SAM)P8 mice, a murine model of senescence, and mice of the control SAMR1 strain with lithium. The treatment reduced hippocampal caspase 3 and calpain activation, indicating that it provides neuroprotection. Lithium also reduced both the levels and activity of GSK-3beta and the activity of cyclin-dependent kinase 5 and reduced hyperphosphorylation of 3 different phosphoepitopes of tau: Ser199, Ser212, and Ser396. In lithium-treated primary cultures of SAMP8 and SAMR1 cerebellar neurons, there was a marked reduction in protease activity mediated by calpain and caspase 3. Both lithium and SB415286, a specific inhibitor of GSK-3beta, reduced apoptosis in vitro. Taken together, these in vivo and in vitro findings of lithium-mediated reductions in GSK-3beta and cyclin-dependent kinase 5 activities, tau phosphorylation, apoptotic activity, and cell death provide a strong rationale for the use of lithium as a potential treatment in neurodegenerative diseases.

Senescence-Accelerated Mouse (SAM) Strains Have a Spontaneous Mutation in the Abcb1a Gene

Senescence-Accelerated Mouse (SAM) strains are used as animal models for gerontological research. Here, we report that the SAMR1 strain, which shows a high sensitivity to toxicity of the parasiticide ivermectin, has a spontaneous retroviral insertional mutation in the ATP-binding cassette, sub-family B (MDR/TAP), member 1A (Abcb1a) gene. This mutation is identical to that found in Crl:CF1-Abcb1a mice, which are also highly sensitive to ivermectin due to the mutation. The mutant Abcb1a allele was found in SAMR4, SAMR5, SAMP1, SAMP6, SAMP7, and SAMP9, but not in SAMP3, SAMP8, SAMP10, SAMP11, and other outbred and inbred strains, including 129/SvJ strains. These results impart both caution and promise in the use of SAM strains in studies of biological processes in which P-glycoprotein participates.

Consistency of low bone density across bone sites in SAMP6 laboratory mice.

The development of bone densitometry has made it clear that there are discrepancies in bone density at various measurement sites in a given individual. This study examined the consistency of bone density measurements across various sites in a strain of laboratory mouse (senescence-accelerated mouse; SAM). A systemic evaluation of the bone density was performed by dual-energy X-ray absorptiometry (DXA) on SAMP6 (P6) mice, a strain with low peak bone density, as measured by microphotodensitometry of the femoral bones, whereas the SAMP2 (P2) and SAMR1 (R1) strains have high peak bone density. We modified Jilka's method to more comprehensively measure the whole body and additional regions of interest (ROIs; head, right foreleg, left foreleg, right hindleg, left hindleg, spine, and tail). The age-related changes in the total (whole-body) BMD showed a common pattern among the strains studied, and the peak value was seen at 4 months old. P6 showed the lowest peak BMD. A detailed comparison of the bone density between P6 and P2 at the age of 4 months revealed significantly lower regional BMD values for P6 in all seven ROIs. The strain difference in BMD could not be attributed to a difference in size. In conclusion, P6 mice showed low bone density not only in their femurs but also in the subregions and over their entire body. This strain can be potentially useful in the investigation of the genetic basis of senile osteoporosis.

Mitochondrial dysfunction and an impaired response to higher oxidative status accelerate cellular aging in SAMP strains of mice

The senescence accelerated mouse (SAM) strains consist of a series of SAMP and SAMR strains. When compared with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter life-span, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans. Many of the pathological phenotypes that old SAMP mice display can be classified as age-dependent disorders and are thought to be “a direct consequence of physiological senescence. ” A higher oxidative status and mitochondrial dysfunction were observed in various organs from SAMP strains of mice. This senescence acceleration is also observed in vitro in cultures of isolated dermal fibroblast-like cells from SAMP11 mice and was associated with a higher oxidative status. The greater production of reactive oxygen species (ROS) was thought to be partly caused by mitochondrial dysfunction rather than by the impaired induction of antioxidative enzymes. These dysfunctional mitochondria had an abnormal appearance, and we observed similar morphological abnormalities in various tissues from old SAMP mice. These observations suggest that one cause of the senescence acceleration and the age-dependent alterations in cell structure and function was the higher oxidative status caused by mitochondrial dysfunction.

Diurnal rhythm disorder of behavioral activity in SAMP1 mice is partially normalized by spontaneous wheel running

We examined the diurnal rhythms of food and water intake, spontaneous wheel running (SWR), and spontaneous motor activity (SMA) in the SAMP1 strain, a mouse model of accelerated senescence. Without SWR exercise, food, and water intake in the SAMP1 mice was significantly higher during the light (L)-phase of the light–darkness (LD) cycle than in the control SAMR1 strain. Additionally, SWR and SMA activity rhythms were split in SAMP1 mice, as demonstrated by the appearance of a secondary peak starting from the end of the dark (D)-phase. SWR exercise significantly increased the percentages of nocturnal food and water intake and SMA in the SAMP1 mice, although food and water intake did not reach the level of control SAMR1 mice. Thus, the disordered diurnal rhythms in SAMP1 mice can be normalized, even if only partially, by SWR exercise.

Higher Expression of Collagen-binding Small Leucine-rich Proteoglycan Genes in Mouse Mandibular Bone Marrow than Femoral Bone Marrow

Although the craniofacial and the appendicular bones develop embryologically from different origins and show different architectures and functions, it is still unclear if there exist site-specific genetic and phenotypic differences in these bones. The aim of this study was to analyze the gene expression levels of collagen-binding small leucine-rich proteoglycans (SLRPs) and type I collagen (COLI), the major matrix proteins in bone, in mouse mandibular and femoral bone marrows. Histomorphometrical and real-time PCR analyses were performed on the two bones of two senescence-accelerated mouse (SAM) strains. SAMP8 and SAMR1, with potentially different bone phenotypes. In both mice, the trabecular bone volume was 10 times higher at the mandibular neck than at the femoral distal metaphysis. The volume in the femur but not in the mandible was slightly higher in SAMR1 than in SAMP8. The mRNAs of COLI and collagen-binding SLRPs, except decorin, were higher in the mandibular bone marrow than in the femoral marrow. Although the femoral marrow did not express fibromodulin and lumican in both mouse strains and biglycan in the SAMR1 strain, they were highly expressed in the mandibular marrow. High gene expression of these molecules in the mandibular bone may imply active bone formation and remodeling in this bone tissue.

A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice

The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions.

Biological model of accelerated senescence. II. Age-related changes in the number of developing male germ cells and Sertoli cells in gonads of senescence-accelerated mice

It was shown that in immature three- to four-week-old mice prone to accelerated senescence (SAMP1 strain), the number of spermatogonia, pachytene spermatocytes, and circular spermatids exceeded that in mice resistant to accelerated senescence (SAMR1 strain) by more than two times. Differences were found in the pattern of age-related changes in the number of meiotic and postmeiotic cells in the sexually mature SAMP1 and SAMR1 mice. In the gonads of SAMP1 and SAMR1 mice, the number of Sertoli cells was unstable.

A Morphological and Morphometrical Study of the Retina in Aging SAM Mice

We investigated whether neuronal cell loss occurred as a part of normal aging of the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in the BALB/c mouse. All three strains showed age-related atrophy of the retina after histologically normal development. Morphometrical study revealed the following facts. The rate of loss of photoreceptor cells in the peripheral retina was greater than in the central retina in all three strains. In the central retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and SAMR1 mice than in the BALB/c mice. In the peripheral retina, the SAMR1 and SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of loss of these cells did not differ among the three strains. The rate of loss of ganglion cells did not differ between the peripheral and central retinas in the three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the peripheral retina than the BALB/c strain at all ages. Because the rate of age-related loss of these cells in SAMP1 mice was not accelerated, and they were short-lived, SAMP1 mice did not show marked age-related loss. On the contrary, the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells late in life because of their longer life span, and we propose that this strain is a suitable animal model for the study of mechanisms of age-related loss of neuronal cells in the retina.