PMID- 32990683
OWN - NLM
STAT- MEDLINE
DCOM- 20210607
LR  - 20210607
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 5
IP  - 21
DP  - 2020 Nov 5
TI  - Acarbose has sex-dependent and -independent effects on age-related physical 
      function, cardiac health, and lipid biology.
LID - 137474 [pii]
LID - 10.1172/jci.insight.137474 [doi]
LID - e137474
AB  - 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.
FAU - Herrera, Jonathan J
AU  - Herrera JJ
AD  - Department of Molecular & Integrative Physiology, University of Michigan (UM), 
      Ann Arbor, Michigan, USA.
FAU - Louzon, Sean
AU  - Louzon S
AD  - Department of Molecular & Integrative Physiology, University of Michigan (UM), 
      Ann Arbor, Michigan, USA.
FAU - Pifer, Kaitlyn
AU  - Pifer K
AD  - Department of Pathology, UM Medical School, Ann Arbor, Michigan, USA.
FAU - Leander, Danielle
AU  - Leander D
AD  - Department of Pathology, UM Medical School, Ann Arbor, Michigan, USA.
FAU - Merrihew, Gennifer E
AU  - Merrihew GE
AD  - Department of Genome Sciences and.
FAU - Park, Jea H
AU  - Park JH
AD  - Department of Genome Sciences and.
FAU - Szczesniak, Kate
AU  - Szczesniak K
AD  - Department of Molecular & Integrative Physiology, University of Michigan (UM), 
      Ann Arbor, Michigan, USA.
FAU - Whitson, Jeremy
AU  - Whitson J
AD  - Department of Pathology, University of Washington, Seattle, Washington, USA.
FAU - Wilkinson, John E
AU  - Wilkinson JE
AD  - Unit for Laboratory Animal Medicine and Department of Pathology, UM, Ann Arbor, 
      Michigan, USA.
FAU - Fiehn, Oliver
AU  - Fiehn O
AD  - UCD, Genome Center, Davis, California, USA.
FAU - MacCoss, Michael J
AU  - MacCoss MJ
AD  - Department of Genome Sciences and.
FAU - Day, Sharlene M
AU  - Day SM
AD  - Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 
      USA.
FAU - Miller, Richard A
AU  - Miller RA
AD  - Department of Pathology, UM Medical School, Ann Arbor, Michigan, USA.
AD  - UM Geriatrics Center, Ann Arbor, Michigan, USA.
FAU - Garratt, Michael
AU  - Garratt M
AD  - Department of Pathology, UM Medical School, Ann Arbor, Michigan, USA.
AD  - Department of Anatomy, School of Biomedical Sciences, University of Otago, 
      Dunedin, New Zealand.
LA  - eng
GR  - P30 AG024824/AG/NIA NIH HHS/United States
GR  - P01 AG001751/AG/NIA NIH HHS/United States
GR  - P30 AR069620/AR/NIAMS NIH HHS/United States
GR  - T32 AG000057/AG/NIA NIH HHS/United States
GR  - P30 AG013280/AG/NIA NIH HHS/United States
GR  - T32 GM007863/GM/NIGMS NIH HHS/United States
GR  - T32 GM008322/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20201105
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Glycoside Hydrolase Inhibitors)
RN  - T58MSI464G (Acarbose)
SB  - IM
MH  - Acarbose/*pharmacology
MH  - Age Factors
MH  - Aging/*drug effects
MH  - Animals
MH  - Cardiomegaly/*drug therapy
MH  - Female
MH  - Glycoside Hydrolase Inhibitors/pharmacology
MH  - Heart/*drug effects
MH  - Lipidoses/*drug therapy/metabolism
MH  - Liver Diseases/*drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - *Physical Conditioning, Animal
MH  - Sex Factors
PMC - PMC7710286
OTO - NOTNLM
OT  - Aging
OT  - Cellular senescence
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2020/09/30 06:00
MHDA- 2021/06/08 06:00
PMCR- 2020/11/05
CRDT- 2020/09/29 12:36
PHST- 2020/03/26 00:00 [received]
PHST- 2020/09/23 00:00 [accepted]
PHST- 2020/09/30 06:00 [pubmed]
PHST- 2021/06/08 06:00 [medline]
PHST- 2020/09/29 12:36 [entrez]
PHST- 2020/11/05 00:00 [pmc-release]
AID - 137474 [pii]
AID - 10.1172/jci.insight.137474 [doi]
PST - epublish
SO  - JCI Insight. 2020 Nov 5;5(21):e137474. doi: 10.1172/jci.insight.137474.