Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging

Abstract

SummaryPeripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age-associated alterations in glial and axonal proteins in vivo . Although calorie restriction is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8, 18, 29 and 38 months) kept on an ad libitum (AL) or a 40% calorie restricted diet. Age-associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention, which is paralleled with the maintenance of a differentiated Schwann cell phenotype. The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagylysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age-limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health.

Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

“…Brain specific knockout of ATG7 or ATG5 leads to neurodegeneration with loss of purkinje cells in the cerebellum (Hara et al, 2006;Komatsu et al, 2006). In humans, decreased autophagy has been implicated in several neurodegenera tive diseases (Martinez Vicente and Cuervo, 2007), and in creased autophagy attenuates aspects of neurodegeneration (Chen et al, 2008;Rangaraju et al, 2009). Based on the evi dence that increased autophagy may lead to life extension and autophagy (Carreira et al, 2010).…”

Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling

“…For example, numerous studies indicate that nerve regeneration and myelination after injury are impaired in diabetic neuropathy (5)(6)(7)(8). Moreover, SC myelination can be altered by changes in nutrition (9,10). These findings give rise to the idea that abnormal metabolic conditions could lead to aberrant myelination via abnormalities in SC function.…”

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

“…Such treatment (Carter et al 2007;Fontana 2009) induces both changes shared by all tissues as well as marked tissue-specific effects (Anderson and Weindruch 2010;Kim et al 2008;Opalach et al 2010;Rangaraju et al 2009;Seo et al 2006). The common changes include: (a) coordinated increase in the expression of genes involved in the mitochondrial energy metabolism; (b) improved sensitivity of insulin signaling; (c) increased levels of the circulating adipokine, adiponectin, which counteract some wellrecognized features of the aging process.…”