Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice

Yuan, Rong; Musters, K.; Zhu, Yun; Evans, Tracy R.; Sun, Yujie; Chesler, Elissa J.; Peters, Luanne L.; Harrison, David E.; Bartke, Andrzej

doi:10.1111/acel.13263

Cited by 31 publications

(34 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To compare neuropathology and neuroinflammatory signatures in BALB/c and C57BL/6 mice during chronic infection, NanoString analysis was conducted on BALB/c mouse brain RNA using the same time points of infection as before. Results of merged BALB/c vs. C57BL/6 analysis demonstrate initial differences in gene expression between naïve mice ( Figure 6A ) consistent with previous analysis ( Sellers et al., 2011 ; Yuan et al., 2020 ). In contrast to B6 mice which generally show a continued increase in gene change over the course of infection, BALB/c mice exhibit the largest change at 14dpi which then returns to patterns similar to naïve at chronic infection.…”

Section: Resultssupporting

confidence: 89%

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Bergersen

Barnes

Worth

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Toxoplasma gondii is a resilient parasite that infects a multitude of warm-blooded hosts and results in a lifelong chronic infection requiring continuous responses by the host. Chronic infection is characterized by a balanced immune response and neuropathology that are driven by changes in gene expression. Previous research pertaining to these processes has been conducted in various mouse models, and much knowledge of infection-induced gene expression changes has been acquired through the use of high throughput sequencing techniques in different mouse strains and post-mortem human studies. However, lack of infection time course data poses a prominent missing link in the understanding of chronic infection, and there is still much that is unknown regarding changes in genes specifically relating to neuropathology and resulting repair mechanisms as infection progresses throughout the different stages of chronicity. In this paper, we present a targeted approach to gene expression analysis during T. gondii infection through the use of NanoString nCounter gene expression assays. Wild type C57BL/6 and BALB/c background mice were infected, and transcriptional changes in the brain were evaluated at 14, 28, and 56 days post infection. Results demonstrate a dramatic shift in both previously demonstrated and novel gene expression relating to neuropathology and resolution in C57BL/6 mice. In addition, comparison between BALB/c and C57BL/6 mice demonstrate initial differences in gene expression that evolve over the course of infection and indicate decreased neuropathology and enhanced repair in BALB/c mice. In conclusion, these studies provide a targeted approach to gene expression analysis in the brain during infection and provide elaboration on previously identified transcriptional changes and also offer insights into further understanding the complexities of chronic T. gondii infection.

show abstract

Section: Resultssupporting

confidence: 89%

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Bergersen

Barnes

Worth

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Lifespan studies of the ITP demonstrate that, when following precise standards, mouse lifespan can be reproducibly extended by drugs in the diet (Harrison et al, 2009(Harrison et al, , 2014(Harrison et al, , 2019Miller et al, 2011Miller et al, , 2014Miller, Harrison, et al, 2020;Strong et al, 2008Strong et al, , 2016.…”

Section: F I G U R E 3 Lifespan Curves Of Controls and The 4 Interventions Without Effects/mentioning

confidence: 99%

“…The 2015 cohort of UM-HET3 mice was also used to test the effects of canagliflozin, an inhibitor of SGLT2 (Miller, Harrison, et al, 2020).…”

Section: Control and Experimental Dietsmentioning

confidence: 99%

“…ITP studies are conducted simultaneously at The University of Texas (UT), University of Michigan (UM), and The Jackson Laboratory (TJL) in Bar Harbor, ME. Details of the ITP design have been published (Harrison et al, 2009;Harrison et al, 2014;Harrison et al, 2019;Macchiarini et al, 2020;Miller et al, 2011Miller et al, , 2014Miller, Harrison, et al, 2020;Strong et al, 2008Strong et al, , 2016Strong et al, , 2020. Interventions that are found, in an initial experiment, to increase lifespan are then subsequently tested for physiological and pathological changes with age.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Second, we found some sex‐specific loci related to longevity. Numerous studies have reported remarkable sex differences in longevity and life span (Austad & Fischer, 2016; Candore et al, 2006; Ostan et al, 2016; Yuan et al, 2020); however, very few studies have reported the sex‐differential effect of genetics for longevity. TOMM40/APOE is well‐characterized longevity locus that could be split into 4 LD blocks.…”

Section: Discussionmentioning

confidence: 99%

Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals

Liu

Song

et al. 2021

Aging Cell

View full text Add to dashboard Cite

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10−15) and TMEM43/XPC (rs1043943; p = 3.59 × 10−8), were identified in a case–control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10−15) and BMPER (rs17169634; p = 1.45 × 10−10) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex‐stratified analyses identified sex‐specific longevity genes. Notably, sex‐differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not‐longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.

show abstract

Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 31 publications

References 47 publications

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals

Contact Info

Product

Resources

About