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- Ferrara, Maria Cristina, et al.
(författare)
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Sustained improvement of intrinsic capacity in community-dwelling older adults : The plus AGIL Barcelona multidomain program
- 2023
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Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 294:6, s. 730-742
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDifferent programs promote healthy ageing through the optimization of intrinsic capacity. However, a major challenge is to assess their sustained effects over time. +AGIL Barcelona, a consolidated multidomain program, aims to optimize older adults' intrinsic capacity through a coordinated approach among primary care, geriatrics and community resources, in agreement with the integrated care for older people (ICOPE) guidelines. We aimed to evaluate the +AGIL Barcelona longitudinal effect on older adults' physical performance. MethodsAll +AGIL Barcelona consecutive participants since 2016 were enrolled. After a comprehensive geriatric assessment, a tailored, multidisciplinary intervention aligned with the ICOPE guidelines is offered. It includes a 10-week boost multicomponent exercise program, nutritional and sleep-hygiene counselling, revision and optimization of pharmacological treatments and screening for cognitive impairment, depression and loneliness. Changes in physical performance after 3 and 6 months were assessed using mixed models including baseline frailty degree, time and all potential significant confounders. ResultsWe included 194 participants in the analysis (mean age = 81.6 [standard deviation = 5.8], 68% women). An independent, clinically and statistically significant improvement in physical performance (Short Physical Performance Battery [SPPB] test, combining gait speed, strength and balance) was found at 3 months (SPPB mean change: 1.4; 95% CI: 1.1-1.6) and 6 months (SPPB mean change: 1.1; 95% CI 0.8-1.5). Equivalent results were observed for all the SPPB sub-tests. ConclusionsA coordinated, multidisciplinary and integrated program can benefit older adults' intrinsic capacity. The participants' empowerment and the connection with the available community resources are critical points for a successful intervention.
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| 3. |
- Garcia-Bartolome, Alberto, et al.
(författare)
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Respiratory chain enzyme deficiency induces mitochondrial location of actin-binding gelsolin to modulate the oligomerization of VDAC complexes and cell survival
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:13, s. 2493-2506
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Tidskriftsartikel (refereegranskat)abstract
- Despite considerable knowledge on the genetic basis of mitochondrial disorders, their pathophysiological consequences remain poorly understood. We previously used two-dimensional difference gel electrophoresis analyses to define a protein profile characteristic for respiratory chain complex III-deficiency that included a significant overexpression of cytosolic gelsolin (GSN), a cytoskeletal protein that regulates the severing and capping of the actin filaments. Biochemical and immunofluorescence assays confirmed a specific increase of GSN levels in the mitochondria from patients' fibroblasts and from transmitochondrial cybrids with complex III assembly defects. A similar effect was obtained in control cells upon treatment with antimycin A in a dose-dependent manner, showing that the enzymatic inhibition of complex III is sufficient to promote the mitochondrial localization of GSN. Mitochondrial subfractionation showed the localization of GSN to the mitochondrial outer membrane, where it interacts with the voltage-dependent anion channel protein 1 (VDAC1). In control cells, VDAC1 was present in five stable oligomeric complexes, which showed increased levels and a modified distribution pattern in the complex III-deficient cybrids. Downregulation of GSN expression induced cell death in both cell types, in parallel with the specific accumulation of VDAC1 dimers and the release of mitochondrial cytochrome c into the cytosol, indicating a role for GSN in the oligomerization of VDAC complexes and in the prevention of apoptosis. Our results demonstrate that respiratory chain complex III dysfunction induces the physiological upregulation and mitochondrial location of GSN, probably to promote cell survival responses through the modulation of the oligomeric state of the VDAC complexes.
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