Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose

Zhou, Yueyue; Ji, Xiong-Fei; Fu, Jianping; Zhu, Xiaojuan; Li, Ronghua; Mu, Changkao; Song, Weiwei

doi:10.1371/journal.pone.0132088

Cited by 43 publications

(55 citation statements)

References 63 publications

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“…Recently, studies focused on the roles of galactose in cellular senescence have shown that the mechanisms underlying d -gal -induced aging likely involve glucose and 1ipid metabolic disorders, increased oxidative damage, the accumulation of advanced glycation end products, impaired elimination of abnormal substances, accelerated cell apoptosis, and enhanced insulin resistance 22,24. The effects produced by d -gal differ with dosage (varying between 50 and 1,250 mg/kg/d), age group (varying between 6 weeks and 6 months), and time interval (varying between 6 and 10 weeks) 12.…”

Section: Discussionmentioning

confidence: 99%

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

Liu¹,

Hu²,

Mao³

et al. 2017

CIA

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BackgroundRecently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis.ObjectiveTo investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats.MethodsTwelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model.ResultsThe mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group.ConclusionHigh-dose- d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

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Section: Discussionmentioning

confidence: 99%

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

Liu¹,

Hu²,

Mao³

et al. 2017

CIA

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“…Galactose treatment was reported to cause increases in lipid peroxides and PC levels and decreases in antioxidant enzyme activities in serum and tissues like liver and brain, together with histopathological changes and progressive deterioration in learning and memory capacity in rodents (Aydın et al., ; Han, Lin, Lee, Liang, & Hou, ; Kalaz et al., ; Xiong et al., ). In addition, some investigators have detected that AGE levels were increased in serum, liver and brain tissues of GAL‐treated rats (Han et al., ; Song et al., ; Xiong et al., ; Zhou et al., ). However, studies investigating the effect of GAL‐induced accelerated ageing on male reproductive organs are quite limited.…”

Section: Discussionmentioning

confidence: 99%

Carnosine prevents testicular oxidative stress and advanced glycation end product formation in D-galactose-induced aged rats

et al. 2017

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D-Galactose is shown to mimic natural ageing in rodents by exacerbating oxidative stress and glycation. Steroid production and having a poor antioxidant system make testis vulnerable to galactose-induced ageing. Antioxidation and antiglycating actions of carnosine may be intriguing for prevention of testicular ageing. In this study, male Wistar rats were applied D-galactose (300 mg/kg; subcutaneously 5 days a week) and carnosine (250 mg/kg; intraperitoneally 5 days a week) along with D-galactose for 2 months. D-Galactose treatment increased testicular reactive oxygen species, thiobarbituric acid reactive substances, diene conjugates, protein carbonyls, advanced oxidation products of proteins and advanced glycation end products. Carnosine was capable of repelling oxidative stress and glycation produced by D-galactose. Johnsen's score, which describes histopathological evaluation, was also significantly improved with preserved spermatogenesis by carnosine. It appears that carnosine deters the testicular oxidative stress due to galactose-induced ageing directly by its antioxidative and antiglycating properties.

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“…Previous evidences indicate that increased reactive oxygen species (ROS) generation is associated with abnormal metabolism such as glucose autoxidation and result in the upregulation of transforming growth factor (TGF)‐β1, extracellular matrix (ECM) which implicated in the progression of cardiac fibrosis . D‐galactose (D‐gal) is a reducing sugar which is most commonly used to study aging‐ related pathological complications . Evidences from various studies suggest that D‐gal produces ROS during its metabolism in vivo and produced advanced glycation end‐products (AGEs) which eventually accelerate the aging process .…”

Section: Introductionmentioning

confidence: 99%

Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D‐galactose induced aging in rats

Chang

Tamilselvi

Lin

et al. 2018

Environmental Toxicology

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Cardiac fibrosis is a common pathophysiological process observed during chronic and stressinduced acceleration of cardiac aging. Fibrosis is a necessary process during wound healing and tissue repair. However, its deposition in organs would proceed to scarring and organ damage.Here Alpinate Oxyphyllae Fructus (AOF), a Chinese medicine extract was used to protect aging heart from collagen accumulation. About 8 weeks old, male SD rats were randomly divided into (i) Control, (ii) D-galactose induced aging (IA), (iii) IA + AOF 50 (AOF low, AL), (iv) IA + AOF 100 (AOF medium, AM), (v) IA + AOF 150 (AOF high, AH) mg/kg/day, AOF was administered orally. After 8 weeks rats were sacrificed and hearts were collected. Results showed collagen deposition and up-regulation of matrix metalloproteinases-MMP-2 and -9 in D-galactoseinduced aging rats. Furthermore, western blotting and immunostaining were also confirmed the upregulation of TGF-β1 mediated fibrosis in aging induced rats. However, collagen deposition and fibrosis were significantly decreased by AOF treatments (AM and AH). AOF treatments salvaged the cardiac fibrosis. Hence, AOF might be a potential therapeutic agent in the prevention of cardiac fibrosis associated with aging. The protective effects of AOF might have promising results in anti-aging treatments.

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Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose

Cited by 43 publications

References 63 publications

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

Carnosine prevents testicular oxidative stress and advanced glycation end product formation in D-galactose-induced aged rats

Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D‐galactose induced aging in rats

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