Analysis Tools
cardiovascular system
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• under basal conditions, aged hearts from 20-old month-old mice exhibit significantly fewer healthy mitochondria and more mildly damaged mitochondria than wild-type hearts while mitochondrial morphology parameters (area, perimeter, aspect ratio, roundness) are largely normal, indicating that fission-fusion dynamics are preserved
• at 1 h after exhaustive exercise, aged hearts exhibit significantly fewer healthy mitochondria and accumulate more moderately/severely damaged mitochondria than wild-type hearts
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• wheat germ agglutinin (WGA) staining indicates increased cardiomyocyte cross-sectional area in aged, but not in young, hearts
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• mice exhibit an age-dependent myocardial hypertrophy with no difference in overall body weight relative to age-matched wild-type controls
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• aged (18- to 22-old month-old) mice show a significant increase in heart weight-to-body weight (HW/BW) ratio relative to age-matched wild-type controls
• however, HW/BW ratio is normal in young (2- to 3-month-old) mice
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• H&E staining indicates an enlarged left ventricular luminal circumference in aged hearts
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• mice exhibit accelerated age-related cardiac dysfunction, mostly affecting diastolic function and ventricular geometry while preserving systolic output
• aged hearts from 18- to 22-old month-old mice show a significant increase in senescence-associated (SA)-beta-gal activity and immunostaining for p21 (a canonical senescence mediator) along with striking lipofuscin accumulation, a hallmark of oxidative injury and defective autophagic clearance
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• aged (18- to 22-old month-old) mice show a significant increase in left ventricular internal diameter during both diastole (LVIDd) and systole (LVIDs), consistent with ventricular dilation
• however, fractional shortening (FS) and ejection fraction (EF) remain unchanged in aged mice and cardiac dimensions and performance are normal in young (2- to 3-month-old) mice
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cellular
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• under basal conditions, aged hearts from 20-old month-old mice exhibit significantly fewer healthy mitochondria and more mildly damaged mitochondria than wild-type hearts while mitochondrial morphology parameters (area, perimeter, aspect ratio, roundness) are largely normal, indicating that fission-fusion dynamics are preserved
• at 1 h after exhaustive exercise, aged hearts exhibit significantly fewer healthy mitochondria and accumulate more moderately/severely damaged mitochondria than wild-type hearts
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• under basal conditions, 20-old month-old mice show mitochondrial abnormalities in the substantia nigra pars compacta (SNc), including a significant increase in mitochondrial aspect ratio and reduced roundness but no change in average mitochondrial area or perimeter
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• 20-old month-old mice show mitochondrial abnormalities in the substantia nigra pars compacta (SNc), including a significant increase in mitochondrial aspect ratio and reduced roundness but no change in average mitochondrial area or perimeter
• however, no overt neurodegeneration is observed and the number of TH-positive dopaminergic neurons per frame is normal in the SNc
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• mouse embryonic fibroblasts (MEFs) show significantly less carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced phosphorylation of ubiquitin at Ser65 (p-S65-Ub), suggesting a defect in the PINK1/Parkin mitophagy pathway; this defect is fully rescued by reintroduction of wild-type MTFR1L but not the MTFR1L R19A/R23A mutant
• under basal conditions, aged hearts from 20-old month-old mice exhibit significantly less mitophagosomes than wild-type hearts, indicating impaired mitophagy
• however, basal mitophagy levels are largely normal in young hearts from 2-month-old mice
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homeostasis/metabolism
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• mouse embryonic fibroblasts (MEFs) show significantly less carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced phosphorylation of ubiquitin at Ser65 (p-S65-Ub), suggesting a defect in the PINK1/Parkin mitophagy pathway; this defect is fully rescued by reintroduction of wild-type MTFR1L but not the MTFR1L R19A/R23A mutant
• under basal conditions, aged hearts from 20-old month-old mice exhibit significantly less mitophagosomes than wild-type hearts, indicating impaired mitophagy
• however, basal mitophagy levels are largely normal in young hearts from 2-month-old mice
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• 2-month-old mice show a marked increase of PRKN (parkin RBR E3 ubiquitin protein ligase) protein levels in the heart but no significant change in PRKN levels in the brain or retina
• notably, protein levels of mitochondrial marker TIM23 (translocase of inner mitochondrial membrane 23) remain unchanged in the heart, brain and retina
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• aged mice show a significant increase in circulating IL-6, a marker of the senescence-associated secretory phenotype
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• at 1 h after exhaustive exercise, aged hearts from 20-old month-old mice exhibit significantly fewer healthy mitochondria and accumulate more moderately/severely damaged mitochondria than wild-type hearts
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• in culture, primary cardiomyocytes isolated from neonatal mice show premature upregulation of senescence markers (p16, p21, gammaH2AX) as early as day 5 (versus day 7 in wild-type controls) along with increased SA-beta-gal staining, indicating accelerated cardiomyocyte senescence
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immune system
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• aged mice show a significant increase in circulating IL-6, a marker of the senescence-associated secretory phenotype
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growth/size/body
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• mice exhibit an age-dependent myocardial hypertrophy with no difference in overall body weight relative to age-matched wild-type controls
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• aged (18- to 22-old month-old) mice show a significant increase in heart weight-to-body weight (HW/BW) ratio relative to age-matched wild-type controls
• however, HW/BW ratio is normal in young (2- to 3-month-old) mice
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muscle
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• under basal conditions, aged hearts from 20-old month-old mice exhibit significantly fewer healthy mitochondria and more mildly damaged mitochondria than wild-type hearts while mitochondrial morphology parameters (area, perimeter, aspect ratio, roundness) are largely normal, indicating that fission-fusion dynamics are preserved
• at 1 h after exhaustive exercise, aged hearts exhibit significantly fewer healthy mitochondria and accumulate more moderately/severely damaged mitochondria than wild-type hearts
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• wheat germ agglutinin (WGA) staining indicates increased cardiomyocyte cross-sectional area in aged, but not in young, hearts
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• mice exhibit an age-dependent myocardial hypertrophy with no difference in overall body weight relative to age-matched wild-type controls
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nervous system
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• 20-old month-old mice show mitochondrial abnormalities in the substantia nigra pars compacta (SNc), including a significant increase in mitochondrial aspect ratio and reduced roundness but no change in average mitochondrial area or perimeter
• however, no overt neurodegeneration is observed and the number of TH-positive dopaminergic neurons per frame is normal in the SNc
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pigmentation
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• aged hearts from 18- to 22-old month-old mice show a striking lipofuscin accumulation, a hallmark of oxidative injury and defective autophagic clearance
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behavior/neurological
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• aged mice show no obvious motor deficits in terms of latency to fall, fall speed, or distance traveled during Rotarod testing
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