Reference SummaryMitchell SJ, Cell Metab 2016 Jun 14;23(6):1093-1112
Title |
Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. | ||||||
Authors |
Mitchell SJ; Madrigal-Matute J; Scheibye-Knudsen M; Fang E; Aon M; Gonzalez-Reyes JA; Cortassa S; Kaushik S; Gonzalez-Freire M; Patel B; Wahl D; Ali A; Calvo-Rubio M; Buron MI; Guiterrez V; Ward TM; Palacios HH; Cai H; Frederick DW; Hine C; Broeskamp F; Habering L; Dawson J; Beasley TM; Wan J; Ikeno Y; Hubbard G; Becker KG; Zhang Y; Bohr VA; Longo DL; Navas P; Ferrucci L; Sinclair DA; Cohen P; Egan JM; Mitchell JR; Baur JA; Allison DB; Anson RM; Villalba JM; Madeo F; Cuervo AM; Pearson KJ; Ingram DK; Bernier M; de Cabo R | ||||||
Journal |
Cell Metab | ||||||
Volume |
23 | ||||||
Issue |
6 | ||||||
Year |
2016 | ||||||
Pages |
1093-1112 | ||||||
Abstract |
Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. | ||||||
Links |
J:256619 – MGI References 27304509 – National Library of Medicine/PubMed |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6J | Adrenal gland - Subcapsular cell hyperplasia | Adrenal gland - Subcapsular cell |
0 |
||
C57BL/6J | Adrenal gland - Subcapsular cell hyperplasia |
|
Adrenal gland - Subcapsular cell |
0 - 2.0 |
|
DBA/2J | Adrenal gland - Subcapsular cell hyperplasia | Adrenal gland - Subcapsular cell |
1.7 - 6.3 |
||
DBA/2J | Adrenal gland - Subcapsular cell hyperplasia |
|
Adrenal gland - Subcapsular cell |
0 - 3.4 |
|
C57BL/6J | Blood vessel hemangiosarcoma | Liver |
0 - 2.0 |
||
C57BL/6J | Blood vessel hemangiosarcoma | Spleen |
0 - 4.0 |
||
C57BL/6J | Blood vessel hemangiosarcoma |
|
Liver |
0 |
|
C57BL/6J | Blood vessel hemangiosarcoma |
|
Spleen |
0 |
|
DBA/2J | Blood vessel hemangiosarcoma | Liver |
0 |
||
DBA/2J | Blood vessel hemangiosarcoma | Spleen |
0 |
||
DBA/2J | Blood vessel hemangiosarcoma |
|
Liver |
0 |
|
DBA/2J | Blood vessel hemangiosarcoma |
|
Spleen |
0 |
|
C57BL/6J | Kidney lesion | Kidney |
2.0 - 10 |
||
C57BL/6J | Kidney lesion |
|
Kidney |
0 - 4.0 |
|
DBA/2J | Kidney lesion | Kidney |
5.0 - 13 |
||
DBA/2J | Kidney lesion |
|
Kidney |
3.3 - 5.2 |
|
C57BL/6J | Leukocyte lymphoma | Heart |
0 |
||
C57BL/6J | Leukocyte lymphoma | Kidney |
6.0 - 14 |
||
C57BL/6J | Leukocyte lymphoma | Liver |
6.0 - 8.0 |
||
C57BL/6J | Leukocyte lymphoma | Spleen |
2.0 - 12 |
||
C57BL/6J | Leukocyte lymphoma | Lung |
8.0 - 20 |
||
C57BL/6J | Leukocyte lymphoma |
|
Heart |
0 |
|
C57BL/6J | Leukocyte lymphoma |
|
Kidney |
0 - 4.0 |
|
C57BL/6J | Leukocyte lymphoma |
|
Liver |
0 - 8.0 |
|
C57BL/6J | Leukocyte lymphoma |
|
Spleen |
0 - 4.0 |
|
C57BL/6J | Leukocyte lymphoma |
|
Lung |
0 - 2.0 |
|
DBA/2J | Leukocyte lymphoma | Heart |
0 - 1.6 |
||
DBA/2J | Leukocyte lymphoma | Kidney |
0 - 4.8 |
||
DBA/2J | Leukocyte lymphoma | Liver |
0 - 4.8 |
||
DBA/2J | Leukocyte lymphoma | Spleen |
0 - 4.8 |
||
DBA/2J | Leukocyte lymphoma | Lung |
1.7 - 3.2 |
||
DBA/2J | Leukocyte lymphoma |
|
Heart |
0 |
|
DBA/2J | Leukocyte lymphoma |
|
Kidney |
1.6 - 5.2 |
|
DBA/2J | Leukocyte lymphoma |
|
Liver |
0 - 5.2 |
|
DBA/2J | Leukocyte lymphoma |
|
Spleen |
0 - 5.2 |
|
DBA/2J | Leukocyte lymphoma |
|
Lung |
0 - 6.8 |
|
C57BL/6J | Liver carcinoma | Liver |
0 - 2.0 |
||
C57BL/6J | Liver carcinoma |
|
Liver |
0 |
|
DBA/2J | Liver carcinoma | Liver |
0 |
||
DBA/2J | Liver carcinoma |
|
Liver |
0 |
|
C57BL/6J | Liver cyst | Liver |
0 |
||
C57BL/6J | Liver cyst |
|
Liver |
0 |
|
DBA/2J | Liver cyst | Liver |
0 |
||
DBA/2J | Liver cyst |
|
Liver |
0 - 1.7 |
|
C57BL/6J | Liver lesion | Liver |
0 - 12 |
||
C57BL/6J | Liver lesion |
|
Liver |
0 - 26 |
|
DBA/2J | Liver lesion | Liver |
1.6 - 5.0 |
||
DBA/2J | Liver lesion |
|
Liver |
0 - 3.4 |
|
C57BL/6J | Lung adenoma | Lung |
0 - 2.0 |
||
C57BL/6J | Lung adenoma |
|
Lung |
0 |
|
DBA/2J | Lung adenoma | Lung |
1.6 - 3.3 |
||
DBA/2J | Lung adenoma |
|
Lung |
0 |
|
C57BL/6J | Lung tumor - malignant | Lung |
2.0 - 4.0 |
||
C57BL/6J | Lung tumor - malignant |
|
Lung |
0 - 2.0 |
|
DBA/2J | Lung tumor - malignant | Lung |
1.6 - 1.7 |
||
DBA/2J | Lung tumor - malignant |
|
Lung |
0 |
|
C57BL/6J | Spleen tumor | Spleen |
0 - 6.0 |
||
C57BL/6J | Spleen tumor |
|
Spleen |
0 - 10 |
|
DBA/2J | Spleen tumor | Spleen |
0 - 1.6 |
||
DBA/2J | Spleen tumor |
|
Spleen |
0 - 5.2 |