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- Chimienti, Guglielmina, et al.
(author)
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The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver
- 2021
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:4
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Journal article (peer-reviewed)abstract
- Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.
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| 2. |
- Jephthah, Stephanie, et al.
(author)
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Force Field Effects in Simulations of Flexible Peptides with Varying Polyproline II Propensity
- 2021
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In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 17:10, s. 6634-6646
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Journal article (peer-reviewed)abstract
- Five peptides previously suggested to possess polyproline II (PPII) structure have here been investigated by using atomistic molecular dynamics simulations to compare how well four different force fields known for simulating intrinsically disordered proteins relatively well (Amber ff99SB-disp, Amber ff99SB-ILDN, CHARM36IDPSFF, and CHARMM36m) can capture this secondary structure element. The results revealed that all force fields sample PPII structures but to different extents and with different propensities toward other secondary structure elements, in particular, the β-sheet and “random coils”. A cluster analysis of the simulations of histatin 5 also revealed that the conformational ensembles of the force fields are quite different. We compared the simulations to circular dichroism and nuclear magnetic resonance spectroscopy experiments and conclude that further experiments and methods for interpreting them are needed to assess the accuracy of force fields in determining PPII structure.
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