Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Elevating Circulating L‐Kynurenine Promotes Frailty in Aging Mice

doi: 10.1002/jcsm.70214

Figure Lengend Snippet: Consumption of a L‐Kyn supplemented diet raises circulating kynurenine levels, and MCK‐PGC1α expression increases expression of kynurenine aminotransferases. (A) Graphical depiction of the experimental timeline. (B) qPCR analysis showing gene expression in the gastrocnemius muscle. (C) Body weight. (D) Percent body fat measured by time‐domain nuclear magnetic resonance. (E) Plasma metabolomics quantification of L‐Kyn, tryptophan (Trp), and the L‐Kyn/Trp ratio. Panels B and E were analysed using two‐way ANOVA. Panels C and D were analysed using a mixed‐model. Mean values obtained from 14‐month‐old C57BL6 ( n = 10/sex) obtained from the National Institute of Aging colony are shown for comparison. Data are presented as mean ± standard deviation.

Article Snippet: Following baseline physical function assessments, mice were randomised to receive the standard chow diet or a L‐Kyn supplemented diet (Envigo Teklad Global 18% Protein Rodent Diet 2918 irradiated pellet supplemented with 150 mg L‐Kyn per kilogram diet), with both diets provided ad libitum.

Techniques: Expressing, Gene Expression, Nuclear Magnetic Resonance, Clinical Proteomics, Comparison, Standard Deviation

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Elevating Circulating L‐Kynurenine Promotes Frailty in Aging Mice

doi: 10.1002/jcsm.70214

Figure Lengend Snippet: Increasing circulating L‐Kyn and MCK‐PCG1α expression alter physical function in an age‐ and sex‐dependent manner. (A) Physical function assessments including treadmill running capacity, cage wheel activity (average daily activity), walking speed (rotorod), and grip strength (forelimb) from male mice. (B) Physical function assessments including treadmill running capacity, cage wheel activity (average daily activity), walking speed (rotorod), and grip strength (forelimb) from female mice. Panels A and B were analysed using three‐way ANOVA. Mean values obtained from 14‐month‐old C57BL6 ( n = 10/sex) obtained from the National Institute of Aging colony are shown for comparison. Data are presented as mean ± standard deviation.

Article Snippet: Following baseline physical function assessments, mice were randomised to receive the standard chow diet or a L‐Kyn supplemented diet (Envigo Teklad Global 18% Protein Rodent Diet 2918 irradiated pellet supplemented with 150 mg L‐Kyn per kilogram diet), with both diets provided ad libitum.

Techniques: Expressing, Activity Assay, Comparison, Standard Deviation

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Elevating Circulating L‐Kynurenine Promotes Frailty in Aging Mice

doi: 10.1002/jcsm.70214

Figure Lengend Snippet: Elevating circulating L‐Kyn levels increased the prevalence of physical frailty, which can be reduced by MCK‐PCG1α expression. (A) Frailty status at 16 months old (prior to intervention) and 24 months old (after diet intervention) in male and female mice. (B) Sarcopenia status of mice at 24 months old using cutoff values obtained from 14‐month‐old adult controls of each sex. Data were analysed using chi‐squared test. Samples sizes are as follows: male WT‐CON ( n = 20), male WT‐KYN ( n = 21), male MCK‐PCG1α‐CON ( n = 17), male MCK‐PCG1α‐KYN ( n = 17), female WT‐CON (n = 20), female WT‐KYN ( n = 23), female MCK‐PCG1α‐CON ( n = 18), and female MCK‐PCG1α‐KYN ( n = 13).

Article Snippet: Following baseline physical function assessments, mice were randomised to receive the standard chow diet or a L‐Kyn supplemented diet (Envigo Teklad Global 18% Protein Rodent Diet 2918 irradiated pellet supplemented with 150 mg L‐Kyn per kilogram diet), with both diets provided ad libitum.

Techniques: Expressing

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Elevating Circulating L‐Kynurenine Promotes Frailty in Aging Mice

doi: 10.1002/jcsm.70214

Figure Lengend Snippet: Contractile properties of the soleus in situ are unaffected in mice consuming a L‐Kyn supplemented diet. Soleus mass in absolute values and relative to body mass in (A) male and (B) female mice. (C) Maximum absolute and specific force, peak power at 35% of maximal force, muscle fatigue, and motor unit number estimation in male mice. (D) Maximum absolute and specific force, peak power at 35% of maximal force, muscle fatigue, and motor unit number estimation in female mice. Data were analysed using two‐way ANOVA. Mean values obtained from 14‐month‐old C57BL6 ( n = 10/sex) obtained from the National Institute of Aging colony are shown for comparison. Data are presented as mean ± standard deviation.

Article Snippet: Following baseline physical function assessments, mice were randomised to receive the standard chow diet or a L‐Kyn supplemented diet (Envigo Teklad Global 18% Protein Rodent Diet 2918 irradiated pellet supplemented with 150 mg L‐Kyn per kilogram diet), with both diets provided ad libitum.

Techniques: In Situ, Comparison, Standard Deviation

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Elevating Circulating L‐Kynurenine Promotes Frailty in Aging Mice

doi: 10.1002/jcsm.70214

Figure Lengend Snippet: Elevated circulating L‐Kyn and MCK‐PGC1α induce histological changes in the aged soleus muscle. (A) Representative images of labelled cross sections of the soleus muscle and the percentage of type I myofibres in male mice. (B) Mean myofibre cross‐sectional area (CSA) of type I and IIa myofibres in male mice. (C) Representative images of labelled cross sections of the soleus muscle and the percentage of type I myofibres in female mice. (D) Mean myofibre CSA of type I and IIa myofibres in female mice. (E) Gross images of hindlimb muscles. Data were analysed using two‐way ANOVA. Mean values obtained from 14‐month‐old C57BL6 ( n = 10/sex) obtained from the National Institute of Aging colony are shown for comparison. Data are presented as mean ± standard deviation.

Article Snippet: Following baseline physical function assessments, mice were randomised to receive the standard chow diet or a L‐Kyn supplemented diet (Envigo Teklad Global 18% Protein Rodent Diet 2918 irradiated pellet supplemented with 150 mg L‐Kyn per kilogram diet), with both diets provided ad libitum.

Techniques: Muscles, Comparison, Standard Deviation

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Elevating Circulating L‐Kynurenine Promotes Frailty in Aging Mice

doi: 10.1002/jcsm.70214

Figure Lengend Snippet: Elevated circulating L‐Kyn and MCK‐PGC1α alter muscle mitochondrial energetics in aging mice. (A) Mitochondrial OXPHOS function in male mice. (B) Mitochondrial membrane potential and respiratory efficiency in male mice. (C) Mitochondrial H 2 O 2 emitting potential in male mice. (D) Mitochondrial OXPHOS function in female mice. (E) Mitochondrial membrane potential and respiratory efficiency in female mice. (F) Mitochondrial H 2 O 2 emitting potential in female mice. Data were analysed using two‐way ANOVA. Mean values obtained from 14‐month‐old C57BL6 ( n = 10/sex) obtained from the National Institute of Aging colony are shown for comparison. Data are presented as mean ± standard deviation.

Article Snippet: Following baseline physical function assessments, mice were randomised to receive the standard chow diet or a L‐Kyn supplemented diet (Envigo Teklad Global 18% Protein Rodent Diet 2918 irradiated pellet supplemented with 150 mg L‐Kyn per kilogram diet), with both diets provided ad libitum.

Techniques: Membrane, Comparison, Standard Deviation