Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice.

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging Mouse Model.

BACKGROUND: Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. PURPOSE: We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. METHOD: Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. RESULTS: Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. CONCLUSIONS: Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.

Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model.

Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1ß, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-α, IL-1ß, NFκB2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a protective effect on age-induced damage.

[Development of osteoporosis in prematurely aging OXYS rats].

The early osteoporosis in OXYS rats is the presentation of accelerated senescence and earlier positioned as senile. The present study shows the changes in metabolism detected in OXYS rats in the postnatal period. They lead to the development of osteoporosis in future and may underlie the formation of reduced peak bone mass. 90 males OXYS rats used in this study aged from 10 days to 24 months and the control group consisted of 90 male Wistar rats of the matched ages. No differences in BMD in OXYS and Wistar rats at the age of 10 days and 3 months was revealed. At the age of 10 days the OXYS rats showed the higher by 40% activity of ALH--the marker of osteoblast activity--than Wistar rats; but at the age of 3 months ALH activity in OXYS was lower than in Wistar rats. The peak bone mass and BMD in Wistar rats is formed by the age of 12 months, in OXYS rats already by 6, but it did not reach the level of Wistar. The content of Ca in the blood and bone tissue changes similarly: no difference in young age, but reduces in OXYS rats after 6 months to the background of enhanced Ca excretion in urine. However, changing the mineral composition of bone in OXYS rats did not affect the mechanical strength: the absolute strength of the long bones in OXYS at 12 months was lower than that of Wistar, but at the expense of decrease by 1,7 times the cross-sectional area. We suppose that genetically determined hypoplasia of the bone tissue in OXYS rats is the starts of pathogenetic mechanisms of idiopathic osteoporosis.

[Radiation-protective action of bioantioxidant complex of ginseng extract in the model of the radiation-induced aging during development of radiation-induced neoplasms].

The study of the geriatric properties of the bioantioxidant complex "Neovitin" received from a biomass of ginseng, against formation of radio gene tumors was continued. The preparation was applied to the laboratory animals exposed to chronic gamma irradiation by low doses, by all period of irradiation and thirty days in the post beam period. The expressed anticancerogenic effect of "Neovitin", reducing formation of radio gene tumors, including malignant, as well as reduction of a spectrum of new growths were proved.

Omega-3 polyunsaturated fatty acids ameliorate the severity of ileitis in the senescence accelerated mice (SAM)P1/Yit mice model.

Clinical studies using omega-3 polyunsaturated fatty acids (omega3-PUFA) to Crohn's disease (CD) are conflicting. Beneficial effects of dietary omega3-PUFA intake in various experimental inflammatory bowel disease (IBD) models have been reported. However, animal models of large intestinal inflammation have been used in all previous studies, and the effect of omega3 fat in an animal model of small intestinal inflammation has not been reported. We hypothesized that the effects of omega3 fat are different between large and small intestine. The aim of this study was to determine whether the direct effect of omega3 fat is beneficial for small intestinal inflammation. Senescence accelerated mice (SAM)P1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. The numbers of F4/80-positive monocyte-macrophage cells as well as beta7-integrin-positive lymphocytes in the intestinal mucosa were increased significantly compared with those in the control mice (AKR-J mice). The area of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-positive vessels was also increased. The degree of expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and interferon (IFN)-gamma mRNA were increased significantly compared with those in the control mice. The feeding of two different kinds of omega3 fat (fish-oil-rich and perilla-oil-rich diets) for 16 weeks to SAMP1/Yit mice ameliorated inflammation of the terminal ileum significantly. In both the omega3-fat-rich diet groups, enhanced infiltration of F4/80-positive monocytes/macrophages in intestinal mucosa of SAMP1/Yit mice cells and the increased levels of MCP-1, IL-6 and IFN-gamma mRNA expression were ameliorated significantly compared with those in the control diet group. The results suggest that omega3 fat is beneficial for small intestinal inflammation by inhibition of monocyte recruitment to inflamed intestinal mucosa.

The yin and yang of the Cdkn2a locus in senescence and aging.

Senescence of cultured cells involves activation of the p19(Arf)-p53 and the p16(Ink4a)-Rb tumor suppressor pathways. This, together with the observation that p19(Arf) and p16(Ink4a) expression increases with age in many tissues of humans and rodents, led to the speculation that these pathways drive in vivo senescence and natural aging. However, it has been difficult to test this hypothesis using a mammalian model system because inactivation of either of these pathways results in early death from tumors. One approach to bypass this problem would be to inactivate these pathways in a murine segmental progeria model such as mice that express low amounts of the mitotic checkpoint protein BubR1 (BubR1 hypomorphic mice). These mice have a five-fold reduced lifespan and develop a variety of early-aging associated phenotypes including cachetic dwarfism, skeletal muscle degeneration, cataracts, arterial stiffening, (subcutaneous) fat loss, reduced stress tolerance and impaired wound healing. Importantly, BubR1 hypomorphism elevates both p16(Ink4a) and p19(Arf) expression in skeletal muscle and fat. Inactivation of p16(Ink4a) in BubR1 mutant mice delays both cellular senescence and aging specifically in these tissues. Surprisingly, however, inactivation of p19(Arf) has the opposite effect; it exacerbates in vivo senescence and aging in skeletal muscle and fat. These mouse studies suggest that p16(Ink4a) is indeed an effector of aging and in vivo senescence, but p19(Arf) an attenuator. Thus, the role of the p19(Arf)-p53 pathway in aging and in vivo senescence seems far more complex than previously anticipated.

Beneficial effect of Toona sinensis Roemor on improving cognitive performance and brain degeneration in senescence-accelerated mice.

The purpose of the present study was to examine the effects of Toona sinensis Roemor extracts on antioxidative activities, brain morphological changes and cognitive ability. In an in vitro study, the antioxidant capacities of water extracts from Toona sinensis Roemor leaf (TSL), root (TSR) and bark (TSB) were evaluated by an alpha,alpha-diphenyl-beta-pricryl-hydrazyl radical-scavenging test. The results showed that the scavenging activities of all Toona sinensis Roemor extracts were over 80% at a concentration of 0.625 mg/ml. In an in vivo study, 3-month-old male senescence-accelerated-prone 8 mice were used as the tested subjects and fed four different diets: casein diet or casein diet supplemented with 1% TSL, TSR or TSB extract for 12 weeks. The results showed that the mice supplemented with Toona sinensis Roemor extracts demonstrated significantly less amyloid beta-protein deposition and lower levels of thiobarbituric acid-reactive substances than the control group. All Toona sinensis Roemor diet groups also showed better active shuttle avoidance responses, and higher superoxide dismutase, catalase and glutathione peroxidase activities, than the control group. It can thus be concluded that supplementation with either TSL, TSR or TSB extract could not only reduce the incidence of ss-amyloid plaques, but also improve learning and memory ability in senescence-accelerated-prone 8 mice. This might be due to the beneficial effects of Toona sinensis Roemor extracts on promoting the antioxidative defence system.

Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10).

Green tea catechins (GT-catechins) have been reported to have an antioxidative effect. We investigated the effect of long-term GT-catechin intake on aging and oxidative damage using aged mice with accelerated senescence (SAMP10), a model of brain senescence with cerebral atrophy and cognitive dysfunction. Major atrophy was observed in the rhinencephalon, hippocampus and striatum of 12-month-old untreated SAMP10 mice. Similarly, levels of 8-oxodeoxyguanosine (8-oxodG), a marker of oxidative DNA damage, were higher in these parts of the cerebrum than in the cerebral cortex and liver. GT-catechin intake effectively suppressed such atrophy in 12-month-old SAMP10 mice. A preventive effect of GT-catechin intake on oxidative DNA damage was also observed in the rhinencephalon (an area particularly susceptible to atrophy) at 6 months of age, i.e. during the early stages of atrophy. A suppressive effect of GT-catechin intake on cognitive dysfunction, as determined by the learning time needed to acquire an avoidance response and assessments of working memory in a Y-maze, was also found in 12-month-old mice. These results suggest that GT-catechin intake partially improves the morphologic and functional alterations that occur naturally in the brains of aged SAMP10 mice.

Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis.

SAMP6, a substrain of senescence-accelerated mice, was developed as an animal model for senile osteoporosis. In the present study, we investigated the bone morphology, together with serum calcium and bone mineral density (BMD) in SAMP6 and age-matched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum compositions and bone morphology. As compared with SAMR1, BMD, the femoral weight, femoral calcium and phosphorus levels were significantly reduced in SAMP6 at 2 and 5 months of age. The number of osteoblasts in trabecular bones was also significantly reduced. Swollen mitochondria and myelin-like structures were found in osteoblasts and osteocytes of SAMP6 mice at 2 and 5 months of age. There was a greater proportion of resting surface and less forming surface in the femoral endosteal surfaces of SAMP6 mice. The amount of trabecular bone in the lumbar vertebra and the distal metaphysis of the femur was reduced. The number of the mast cells in bone marrow of the tibia significantly increased in SAMP6 mice. These findings indicate that the lower bone mass in SAMP6 was due to the reduction in osteoblast formation and suggested that mast cells in bone marrows play a role in the pathogenesis of senile osteoporosis.