Morphological plasticity of synaptic mitochondria during aging

Bertoni–Freddari, Carlo; Fattoretti, Patrizia; Casoli, Tiziana; Spagna, Carla; Meier‐Ruge, W.; Ulrich, J.

doi:10.1016/0006-8993(93)90955-m

Cited by 86 publications

(79 citation statements)

References 39 publications

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“…The "megamitochondria" we observed have disruptions in their cristae architecture, a condition which was previously noted with cross-linking ATP synthase complexes [72,73]. A general trend in cells of older organisms is a decrease in number and increase in size of the mitochondrial population [70,74]. Marked increase in the percentage of oversized mitochondria with structural abnormalities have been reported in several instances including in RPE cells of advance aged individuals with Fig.…”

Section: Discussionsupporting

confidence: 73%

“…Mitochondria often undergo ultrastructural remodeling to tailor energy output to meet the demands on the cell and their number can vary between cells of the same tissue [68][69][70][71]. The "megamitochondria" we observed have disruptions in their cristae architecture, a condition which was previously noted with cross-linking ATP synthase complexes [72,73].…”

Section: Discussionmentioning

confidence: 52%

“…9 increasing severity [42] of AMD at the synaptic terminals of old rats [75] and in other adverse conditions where cells are exposed to large amounts of free radicals over an extended period [76,77]. The speculation is that numeric loss of mitochondria is due, in part, to impaired duplicative capacity of these organelles and that a shift in size compensates for numbers to keep volume density and area involved in cellular respiration constant during the lifespan of the individual [70,[78][79][80]. mtDNA is highly susceptible to oxidative stress and unlike nuclear DNA, mutations in mtDNA are not repaired.…”

Section: Discussionmentioning

confidence: 99%

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Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Burke

et al. 2010

j ocul biol dis inform

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Impairment of mitochondria function and cellular antioxidant systems are linked to aging and neurodegenerative diseases. In the eye, the retinal pigment epithelium (RPE) is exposed to a highly oxidative environment that contributes to age-related visual dysfunction. Here, we examined changes in mitochondrial function in human RPE cells and sensitivity to oxidative stress with increased chronological age. Primary RPE cells from young (9-20)-, mid-age (48-60)-, and >60 (62-76)-year-old donors were grown to confluency and examined by electron microscopy and flow cytometry using several mitochondrial functional assessment tools. Susceptibility of RPE cells to H 2 O 2 toxicity was determined by lactate dehydrogenase and cytochrome c release, as well as propidium iodide staining. Reactive oxygen species, cytoplasmic Ca 2+ [Ca 2+ ] c , and mitochondrial Ca 2+ [Ca 2+ ] m levels were measured using 2′,7′-dichlorodihydrofluorescein diacetate, fluo-3/AM, and Rhod-2/AM, respectively, adenosine triphosphate (ATP) levels were measured by a luciferin/luciferase-based assay and mitochondrial membrane potential (ΔΨm) estimated using 5,5′,6,6′-tetrachloro 1,1′3,3′-tetraethylbenzimid azolocarbocyanine iodide. Expression of mitochondrial and antioxidant genes was determined by real-time polymerase chain reaction. RPE cells show greater sensitivity to oxidative stress, reduction in expression of mitochondrial heat shock protein 70, uncoupling protein 2, and superoxide dismutase 3, and greater expression of superoxide dismutase 2 levels with increased chronological age. Changes in mitochondrial number, size, shape, matrix density, cristae architecture, and membrane integrity were more prominent in samples obtained from >60 years old compared to midage and younger donors. These mitochondria abnormalities correlated with lower ATP levels, reduced ΔΨm, decreased [Ca 2+ ] c , and increased sequestration of [Ca 2+ ] m in cells with advanced aging. Our study provides evidence for mitochondrial decay, bioenergetic deficiency, weakened antioxidant defenses, and increased sensitivity of RPE cells to oxidative stress with advanced aging. Our findings suggest that with increased severity of mitochondrial decay and oxidative stress, RPE function may be altered in some individuals in a way that makes the retina more susceptible to age-related injury.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Burke

et al. 2010

j ocul biol dis inform

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“…Since mitochondria did not appear swollen in any age group, this finding indicates that mitochondria increase in size with age. Age-related increases in mitochondrial size have been reported in the rat cerebellum [2] and in human [24] and mouse [28] liver (for review see [18]); however, Herbener [7] found no such changes in mouse heart and liver.…”

Section: Discussionmentioning

confidence: 99%

Age-related quantitative changes in mitochondria of satellite cell sheaths enveloping spinal ganglion neurons in the rabbit

Martinelli

Sartori

Ledda

et al. 2003

Brain Research Bulletin

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We studied mitochondria in the satellite cell sheaths which envelope the spinal ganglion neurons of rabbits aged 12, 42, and 79 months. While the mean cytoplasmic volume of satellite cell sheaths did not change significantly with age, the mean percentage of cytoplasmic volume occupied by mitochondria decreased with age. This decrease is mainly due to a reduction in the total mitochondrial mass and only in minor part is a consequence of lipofuscin accumulation. Mitochondrial structure did not change, while mitochondrial size increased with age. Comparison between mitochondria in nerve cell bodies and those in satellite cell sheaths showed that: (1) the mean percentage of cytoplasmic volume occupied by mitochondria was greater in nerve cell bodies than satellite cell sheaths and the ratio between these two percentages remained constant with advancing age; (2) the total mitochondrial mass was much greater in nerve cell bodies than satellite cell sheaths and the ratio between these two values increased with age; (3) the extent of increase of mitochondrial size with age was similar in nerve cell bodies and satellite cell sheaths. The results of the present study suggest that: (1) the ability of satellite cell sheaths to produce energy decreases with age; (2) the decreased ability of sensory neurons in old animals to meet high energy demands may be partly due to the diminished contribution of their associated satellite cell sheaths.

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“…As documented by electron microscopic studies in different tissues, the ultrastructural features of a given mitochondrial population are coupled to the organelles' functional performances and can undergo significant adaptations to the changing environmental conditions (8)(9)(10)(11). Thus, quantitation of mitochondrial morphological parameters, e.g.…”

Section: Introductionmentioning

confidence: 99%

A morphometric study on human muscle mitochondria in aging

Bertoni–Freddari

Fattoretti

Caselli

et al. 2002

AGE

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Mitochondria are dynamic organelles capable of significant changes of their ultrastructural features according to the tissue-specific energy demands. In human biopsies of vastus lateralis and anterior tibialis muscles from young (25.0 _+ 4.4 years), middle-aged (50.4 _+ 7.5 years) and old (75.5+_3.9 years) healthy volunteers, we carried out a morphometric study on subsarcolemmal and intermyofibrillar mitochondria to assess whether age-related alterations of the morphology of these organelles contribute to the muscle performance decay in aging. By computer-assisted methods, we measured: the average area (MAA), the longer diameter (Dmax) and the ratio perimeter to area (pleomorphic index: Plei) of mitochondria. No significant age-related ultrastructural differences were found either in subsarcolemmal or intermyofibrillar organelles. However, in middle-aged as well as in the old group of patients vs. the young one, MAA and Dmax showed a clear trend to decrease, while Plei showed a marked, age-related tendency to increase. Higher percentages of less pleomorphic organelles were found in the youngest group of patients and this was particularly evident in the subsarcolemmal mitochondrial population. In addition to reporting on discrete aspects of mitochondrial ultrastructure, MAA, Dmax and Plei are closely related to each other and provide a reliable index of the muscle mitochondria adaptive response to age. Thus, we interpret our results as indicating a substantial preservation of muscle mitochondrial ultrastructure during aging.

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Morphological plasticity of synaptic mitochondria during aging

Cited by 86 publications

References 39 publications

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Age-related quantitative changes in mitochondria of satellite cell sheaths enveloping spinal ganglion neurons in the rabbit

A morphometric study on human muscle mitochondria in aging

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