ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2020
Brain Protein Synthesis Rates in the UM-HET3 Mouse Following Treatment With Rapamycin or Rapamycin With Metformin.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
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- Latest assessment methods for mitochondrial homeostasis in cognitive diseases.Neural regeneration research · 2024Review
- Underfeeding Alters Brain Tissue Synthesis Rate in a Rat Brain Injury Model.International journal of molecular sciences · 2023Article
- Exercise and mitochondrial remodeling to prevent age-related neurodegeneration.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Review
- Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction.Frontiers in aging · 2022Article
- Inhibition of mTOR by rapamycin does not improve hypoxic pulmonary hypertension-induced right heart failure in old mice.Experimental gerontology · 2021Article
- Tumor burden negatively impacts protein turnover as a proteostatic process in noncancerous liver, heart, and muscle, but not brain.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex.The Journal of nutrition · 2021Article
- Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.Mechanisms of ageing and development · 2021Review
- A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis.Function (Oxford, England) · 2021Article
- Turning strains into strengths for understanding psychiatric disorders.Molecular psychiatry · 2020Review
- Molecular changes associated with spinal cord aging.GeroScience · 2020Article
- TORwards a Victory Over Aging.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Treatment with the mechanistic target of rapamycin (mTOR) inhibitor, rapamycin (RAP), alone and in combination with the antidiabetic drug, metformin (RAP+MET), extends lifespan in mice. The mechanisms underlying lifespan extension are unclear. One possibility is improved capacity for proteostatic maintenance. We have previously characterized peripheral protein synthesis rates following treatment with RAP. However, it is unknown if RAP+MET elicits similar changes, or if either treatment affects protein synthesis in the brain. We hypothesized that 8 weeks of treatment with RAP and RAP+MET would alter brain protein synthesis rates to reflect proteostatic processes. Using the stable isotopic tracer, deuterium oxide (D2O), we demonstrate in UM-HET3 mice that protein synthesis rates measured in whole brain were unaffected by treatment in young male mice, whereas RAP+MET decreased mitochondrial protein synthesis in young females. Conversely, RAP increased mitochondrial protein synthesis rates in older females. Activity through the AMPK/mTOR pathway was affected in a sex-specific manner in young mice, and minimal changes were observed in the older cohort. Thus, we establish D2O for measurements of biogenesis in the brain. These results provide initial insights into the effects of RAP and RAP+MET on brain protein synthesis. Additionally, these data emphasize that responses to slowed aging treatments vary with sex and age.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.