Are Changes of the Cell Membrane Structure Causally Involved in the Aging Process?

Spiteller, Gerhard

doi:10.1111/j.1749-6632.2002.tb02080.x

Cited by 39 publications

(17 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major outcomes of lipid peroxidation in photoreceptors are twofold. First, it promotes the generation of toxic FFA metabolites, which by themselves or in concert with other ligands, promote apoptosis 60, 63–65. Second, changes in the orientation of the acyl chain of peroxidized fatty acids toward the hydrophilic exterior of the lipid bilayer (e.g.…”

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons

Cho

Yeh

et al. 2008

Cell Death Differ

View full text Add to dashboard Cite

Prolonged light exposure is a determinant factor in inducing neurodegeneration of photoreceptors by apoptosis. Yet, the molecular bases of the pathways and components triggering this cell death event are elusive. Here, we reveal a prominent agedependent increase in the susceptibility of photoreceptor neurons to undergo apoptosis under light in a mouse model. This is accompanied by light-induced subcellular changes of photoreceptors, such as dilation of the disks at the tip of the outer segments, prominent vesiculation of nascent disks, and autophagy of mitochondria into large multilamellar bodies. Notably, haploinsufficiency of Ran-binding protein-2 (RanBP2) suppresses apoptosis and most facets of membrane dysgenesis observed with age upon light-elicited stress. RanBP2 haploinsufficiency promotes decreased levels of free fatty acids in the retina independent of light exposure and turns the mice refractory to weight gain on a high-fat diet, whereas light promotes an increase in hydrogen peroxide regardless of the genotype. These studies demonstrate the presence of age-dependent and RanBP2-mediated pathways modulating membrane biogenesis of the outer segments and light-elicited neurodegeneration of photoreceptors. Furthermore, the findings support a mechanism whereby the RanBP2-dependent production of free fatty acids, metabolites thereof or the modulation of a cofactor dependent on any of these, promote apoptosis of photoreceptors in concert with the light-stimulated production of reactive oxygen species. Cell Death and Differentiation ( The retina comprises a well-defined neurocircuitry mediating the capture, processing, and transmission of photon stimuli to high-order processing centers in the brain. The primary neurons of the retina, rod and cone photoreceptors, mediate the physicochemical transduction of light. Although several components of the light transduction cascade promote the degeneration of photoreceptors upon inherited mutations in the cognate genes, 1 light also acts as a powerful inducer of degeneration of these neurons in wild-type mouse strains.2 Neurodegeneration elicited by light and age appears to vary in multiple genetic backgrounds, thus supporting the presence of various genetic modifiers of cell death upon selective stressors. [3][4][5] To date, few loci conferring resistance to light damage have been identified in genetically altered mice. These include mice lacking the expression of Rpe65, Rho, and mice harboring the Rpe65 Leu450Met mutation. [5][6][7][8][9] Although some of these loci appear to have no impact on age-related retinal degeneration, quantitative trait loci have been implicated in age-related retinal degeneration, but the identities of the genes implicated in this process remain elusive.3,4 Regardless, cumulative damage from oxidative stress appears to play a determinant role in the development of age-related phenotypes of photoreceptors in part as the result of marked and uneven oxygen tension and metabolic demands, across the retina, that make photoreceptors particularly ...

show abstract

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons

Cho

Yeh

et al. 2008

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…Therefore, they shield the membrane PUFA against radicals [44]. They react with ROS to either remove or inhibit them.…”

Section: A N T I O X I D a N T D E F E N S E S Y S T E Mmentioning

confidence: 99%

Clinical pharmacology and therapeutic use of antioxidant vitamins

Rodrigo¹,

Guichard

Charles

2007

Fundamemntal Clinical Pharma

105

View full text Add to dashboard Cite

The clinical use of antioxidants has gained considerable interest during the last decade. It was suggested from epidemiological studies that diets high in fruits and vegetables might help decrease the risk of cardiovascular disease. Therefore, supplements of vitamins C and E were applied through protocols aimed to prevent diseases such as atherosclerosis, preeclampsia or hypertension, thought to be mediated by oxidative stress. Despite the biological properties of these vitamins could account for an effective protection, as shown by several clinical and experimental studies, their efficacy remains controversial in the light of some recent clinical trials and meta-analyses. However, the methodology of these studies, criteria for selection of patients, the uncertain extent of progression of the disease when initiating supplementation, the lack of mechanistic studies containing basic scientific aspects, such as the bioavailability, pharmacokinetic properties, and the nature of the antioxidant sources of vitamins, could account for the inconsistency of the various clinical trials and meta-analyses assessing the efficacy of these vitamins to prevent human diseases. This review presents a survey of the clinical use of antioxidant vitamins E and C, proposing study models based on the biological effects of these compounds likely to counteract the pathophysiological mechanisms able to explain the structural and functional organ damage.

show abstract

“…Unless quenched by antioxidants, lipid peroxidation is a self-propagating autocatalytic process producing several potent ROS. It can also generate lipid hydroperoxides (124,335,336), which are more hydrophilic than unperoxidized fatty acyl chains, and these can thus disrupt the membrane structure, altering fluidity and other functional properties of membranes.…”

Section: Membrane Composition and Lipid Peroxidationmentioning

confidence: 99%

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Hulbert¹,

Pamplona²,

Buffenstein

et al. 2007

Physiological Reviews

767

725

View full text Add to dashboard Cite

Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species. When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span. The more limited information for ectothermic animals and treatments that extend life span (e.g., caloric restriction) are also reviewed.

show abstract

Are Changes of the Cell Membrane Structure Causally Involved in the Aging Process?

Cited by 39 publications

References 36 publications

Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons

Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons

Clinical pharmacology and therapeutic use of antioxidant vitamins

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Contact Info

Product

Resources

About