Project description:Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related path- ways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mito- chondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology. Key words: astrocytes; caloric restriction; mitochondria; oxidative stress; RNA microarrays; SAMP8. Primary cultures enriched in astrocytes were obtained from cerebral cortical tissue from 2-day-old SAMP8 and SAMR1 mice. Astrocyte cultures were established and experiments were routinely carried out after 21 days in culture. Established astrocyte cultures of both SAMR1 and SAMP8 consisted of 85-90% astrocytes, 10-15% microglia and 0.1-1% oligodendroglia. Sera from rats subjected to ad libitum (AL) diet and to CR were obtained as described for the establishment of the CR in vitro model (de Cabo et al., 2003). Serum was heat inactivated at 56°C prior to use in astrocyte culture experiments. Treatment in vitro was performed by adding 10% volume CR or AL serum onto the astrocyte culture medium for 48 h, the cells were harvested and RNA was extracted for the microarray studies. Three biological replicates for each condition were done and RNA was extracted for the microarray studies. Please note that SAM models were developed from AKR/J by Kyoto University. Five litters with severe senescence were selected to further propagate and examine these characteristics. Litters that showed normal aging were selected as a senescence-resistant series (R-series). The genetic background of the SAM mice became suspect after the pathological findings were different from the AKR/J mouse. Each SAM model is genetically different. Each SAM colony was acquired by Harlan by Takeda Chemical Ltd. in 2002. And here is the link to the company site. http://www.harlan.com/products_and_services/research_models_and_services/research_models/sam_inbred_mice/samp8tahsd.hl

Project description:This study investigated the effects of TOR1 gene deletion on Saccharomyces cerevisiae through transcriptome analysis of wild-type and tor1Δ mutant cells during exponential development under non-stress circumstances. A significant number of differentially expressed genes (DEGs) were identified in the absence of TOR1, comprising 1665 upregulated genes and 1425 downregulated genes. These findings demonstrate the extensive impact of TOR signaling on several biological processes, including metabolism, stress response, and lifespan regulation. A significant number of differentially expressed genes (DEGs) were identified in the absence of TOR1, comprising 1665 upregulated genes and 1425 downregulated genes. These findings demonstrate the extensive impact of TOR signaling on several biological processes, including metabolism, stress response, and lifespan regulation. A total of 736 DEGs were associated with either replicative lifespan or chronological lifespan, further emphasizing the significance of TOR1 in aging. Although genes associated with glucose transporters and storage were upregulated, glycolytic genes remained unchanged, indicating a metabolic shift towards alternative pathways such as gluconeogenesis and the pentose phosphate pathway. Among these, HXK1 exhibited the highest upregulation in tor1Δ cells, contrasting with HXK2, whose expression remained stable. This suggests that HXK1, typically active under low glucose or caloric restriction, plays a crucial role in reregulating glucose metabolism in the absence of TOR1. The research also identified specific transcription factors, including ADR1, HAP4, and their paralogs, which were upregulated and bound only to the HXK1 promoter, pointing to their regulatory role in this metabolic shift. The findings indicate that TOR1 inactivation triggers nutrient- and energy-sensing mechanisms that redirect cellular resources towards stress adaptation and longevity, highlighting Tor1's crucial function in aging and proposing that modulation of the TOR pathway could be a potential strategy for anti-aging therapies.

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Saccharomyces cerevisiae

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