PMID- 32572088
OWN - NLM
STAT- MEDLINE
DCOM- 20201210
LR  - 20210622
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jun 22
TI  - Age, Sex and Overall Health, Measured As Frailty, Modify Myofilament Proteins in 
      Hearts From Naturally Aging Mice.
PG  - 10052
LID - 10.1038/s41598-020-66903-z [doi]
LID - 10052
AB  - We investigated effects of age, sex and frailty on contractions, calcium 
      transients and myofilament proteins to determine if maladaptive changes 
      associated with aging were sex-specific and modified by frailty. Ventricular 
      myocytes and myofilaments were isolated from middle-aged (~12 mos) and older (~24 
      mos) mice. Frailty was assessed with a non-invasive frailty index. Calcium 
      transients declined and slowed with age in both sexes, but contractions were 
      largely unaffected. Actomyosin Mg-ATPase activity increased with age in females 
      but not males; this could maintain contractions with smaller calcium transients 
      in females. Phosphorylation of myosin-binding protein C (MyBP-C), desmin, 
      tropomyosin and myosin light chain-1 (MLC-1) increased with age in males, but 
      only MyBP-C and troponin-T increased in females. Enhanced phosphorylation of 
      MyBP-C and MLC-1 could preserve contractions in aging. Interestingly, the 
      age-related decline in Hill coefficients (r = -0.816; p = 0.002) and increase in 
      phosphorylation of desmin (r = 0.735; p = 0.010), tropomyosin (r = 0.779; 
      p = 0.005) and MLC-1 (r = 0.817; p = 0.022) were graded by the level of frailty 
      in males but not females. In these ways, cardiac remodeling at cellular and 
      subcellular levels is graded by overall health in aging males. Such changes may 
      contribute to heart diseases in frail older males, whereas females may be 
      resistant to these effects of frailty.
FAU - Kane, Alice E
AU  - Kane AE
AD  - Blavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of 
      Aging Research at Harvard Medical School, Boston, MA, US.
AD  - Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
FAU - Bisset, Elise S
AU  - Bisset ES
AD  - Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
FAU - Keller, Kaitlyn M
AU  - Keller KM
AD  - Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
FAU - Ghimire, Anjali
AU  - Ghimire A
AD  - Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
FAU - Pyle, W Glen
AU  - Pyle WG
AD  - Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
AD  - IMPART team Canada Investigator Network, Saint John, New Brunswick, Canada.
FAU - Howlett, Susan E
AU  - Howlett SE
AD  - Department of Pharmacology, Dalhousie University, Halifax, NS, Canada. 
      susan.howlett@dal.ca.
AD  - Department of Medicine (Geriatric Medicine), Dalhousie University, Halifax, NS, 
      Canada. susan.howlett@dal.ca.
LA  - eng
GR  - MOP 97973/CIHR/Canada
GR  - PGT 162462/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200622
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Carrier Proteins)
RN  - 0 (Desmin)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Mlc1 protein, mouse)
RN  - 0 (Tropomyosin)
RN  - 0 (myosin-binding protein C)
RN  - 9013-26-7 (Actomyosin)
SB  - IM
MH  - Actomyosin/metabolism
MH  - Aging/*metabolism
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Desmin/metabolism
MH  - Female
MH  - Frailty/*metabolism
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Microfilament Proteins/*metabolism
MH  - Models, Animal
MH  - Myocardial Contraction
MH  - Myocytes, Cardiac/*physiology
MH  - Phosphorylation
MH  - Sex Characteristics
MH  - Tropomyosin/metabolism
PMC - PMC7308399
COIS- The authors declare no competing interests.
EDAT- 2020/06/24 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/06/22
CRDT- 2020/06/24 06:00
PHST- 2019/11/27 00:00 [received]
PHST- 2020/05/04 00:00 [accepted]
PHST- 2020/06/24 06:00 [entrez]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/06/22 00:00 [pmc-release]
AID - 10.1038/s41598-020-66903-z [pii]
AID - 66903 [pii]
AID - 10.1038/s41598-020-66903-z [doi]
PST - epublish
SO  - Sci Rep. 2020 Jun 22;10(1):10052. doi: 10.1038/s41598-020-66903-z.