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Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology
- Source :
- JCI insight, vol 5, iss 21, JCI Insight, JCI Insight, Vol 5, Iss 21 (2020)
- Publication Year :
- 2020
- Publisher :
- American Society for Clinical Investigation, 2020.
-
Abstract
- With an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health in later life. Acarbose (ACA), a drug used clinically to treat type 2 diabetes mellitus (T2DM), can extend mouse life span with greater effect in males than in females. Using a genetically heterogeneous mouse model, we tested the ability of ACA to ameliorate functional, pathological, and biochemical changes that occur during aging, and we determined which of the effects of age and drug were sex dependent. In both sexes, ACA prevented age-dependent loss of body mass, in addition to improving balance/coordination on an accelerating rotarod, rotarod endurance, and grip strength test. Age-related cardiac hypertrophy was seen only in male mice, and this male-specific aging effect was attenuated by ACA. ACA-sensitive cardiac changes were associated with reduced activation of cardiac growth–promoting pathways and increased abundance of peroxisomal proteins involved in lipid metabolism. ACA further ameliorated age-associated changes in cardiac lipid species, particularly lysophospholipids — changes that have previously been associated with aging, cardiac dysfunction, and cardiovascular disease in humans. In the liver, ACA had pronounced effects on lipid handling in both sexes, reducing hepatic lipidosis during aging and shifting the liver lipidome in adulthood, particularly favoring reduced triglyceride (TAG) accumulation. Our results demonstrate that ACA, already in clinical use for T2DM, has broad-ranging antiaging effects in multiple tissues, and it may have the potential to increase physical function and alter lipid biology to preserve or improve health at older ages.<br />Acarbose treatment ameliorates age-associated declines in physical function and cardiac structural ageing, changes that are linked to slowed changes in the cardiac lipidome.
- Subjects :
- Male
0301 basic medicine
Aging
Disease
Inbred C57BL
Cardiovascular
Lipidoses
Mice
chemistry.chemical_compound
0302 clinical medicine
skin and connective tissue diseases
Inbred BALB C
Acarbose
media_common
Mice, Inbred BALB C
Mice, Inbred C3H
Liver Disease
Liver Diseases
Age Factors
Heart
General Medicine
Lipidome
Inbred C3H
Physical Conditioning
Heart Disease
030220 oncology & carcinogenesis
Medicine
Female
Research Article
medicine.drug
Drug
medicine.medical_specialty
media_common.quotation_subject
Cardiomegaly
Biology
Cellular senescence
03 medical and health sciences
Sex Factors
Physical Conditioning, Animal
Internal medicine
medicine
Animals
Glycoside Hydrolase Inhibitors
Pathological
Triglyceride
Animal
Prevention
Type 2 Diabetes Mellitus
Lipid metabolism
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
Digestive Diseases
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....617a852dee0348614c33e49520bd0815