Ageing and hearing loss

Xz, Liu; Yan, Denise

doi:10.1002/path.2102

Cited by 270 publications

(198 citation statements)

References 63 publications

(71 reference statements)

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“…Age-related hearing loss (AHL), characterized by a decline of auditory function with increasing age, is associated with attrition of spiral ganglion neurons and sensory hair cells in the cochlea of the inner ear (90,148). Studies have shown that CR delays the onset of AHL and reduces cochlear pathology (141,150) by reducing oxidative stress (150), which plays a major role in AHL (73,149).…”

Section: Sirt3 Prevents Hearing Loss During Crmentioning

confidence: 99%

Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

Kumar

Lombard²

2015

Antioxidants & Redox Signaling

131

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Significance: Maintenance of metabolic homeostasis is critical for cellular and organismal health. Proper regulation of mitochondrial functions represents a crucial element of overall metabolic homeostasis. Mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5) play pivotal roles in promoting this homeostasis by regulating numerous aspects of mitochondrial metabolism in response to environmental stressors. Recent Advances: New work has illuminated multiple links between mitochondrial sirtuins and cancer. SIRT5 has been shown to regulate the recently described post-translational modifications succinyl-lysine, malonyllysine, and glutaryl-lysine. An understanding of these modifications is still in its infancy. Enumeration of SIRT3 and SIRT5 targets via advanced proteomic techniques promises to dramatically enhance insight into functions of these proteins. Critical Issues: In this review, we highlight the roles of mitochondrial sirtuins and their targets in cellular and organismal metabolic homeostasis. Furthermore, we discuss emerging roles for mitochondrial sirtuins in suppressing and/or promoting tumorigenesis, depending on the cellular and molecular context. Future Directions: Currently, hundreds of potential SIRT3 and SIRT5 molecular targets have been identified in proteomic experiments. Future studies will need to validate the major targets of these enzymes, and elucidate how acetylation and/or acylation modulate their functionality. A great deal of interest exists in targeting sirtuins pharmacologically; this endeavor will require development of sirtuin-specific modulators (activators and inhibitors) as potential treatments for cancer and metabolic disease. Antioxid.

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Section: Sirt3 Prevents Hearing Loss During Crmentioning

confidence: 99%

Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

Kumar

Lombard²

2015

Antioxidants & Redox Signaling

131

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“…Hearing loss is a hallmark of mammalian aging and is characterized by a gradual loss of spiral ganglion neurons and sensory hair cells in the cochlea of the inner ear, which is triggered by oxidative damage in these cells (12). Remarkably, CR prevents hearing loss and oxidative damage in wild-type mice, whereas Sirt3-deficient mice are resistant to the effects of CR.…”

Section: Agingmentioning

confidence: 99%

From Sirtuin Biology to Human Diseases: An Update

Sebastián

Satterstrom

Haigis

et al. 2012

Journal of Biological Chemistry

208

159

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Originally rising to notoriety for their role in the regulation of aging, sirtuins are a family of NAD ؉ -dependent enzymes that have been connected to a steadily growing set of biological processes. In addition to regulating aging, sirtuins play key roles in the maintenance of organismal metabolic homeostasis. These enzymes also have primarily protective functions in the development of many age-related diseases, including cancer, neurodegeneration, and cardiovascular disease. In this minireview, we provide an update on the known roles for each of the seven mammalian sirtuins in these areas.Over three-quarters of a century ago, Clive McCay and colleagues first noted that rats kept on a calorie-restricted diet lived longer than freely fed controls (1). Despite the length of time that has elapsed since this discovery, the molecular mechanism that drives this life span extension has remained elusive. Originally described as a silencing factor in yeast (silencing information regulator), the protein Sir2 came out on top in a screen for modulators of yeast life span (2). Moreover, Sir2 was required for the life span of yeast to be extended by calorie restriction (3). These discoveries launched a new field in biology: the study of Sir2 and its homologs in mammals, called sirtuins.Mammals have seven sirtuins (SIRT1-7) that possess NAD ϩ -dependent deacetylase, deacylase, and ADP-ribosyltransferase activities (4). Sirtuins are found in different subcellular locations, including the nucleus (SIRT1, SIRT6, and SIRT7), cytosol (SIRT2), and mitochondria (SIRT3-5), although in some studies, SIRT1 has been found to possess cytosolic activities, and SIRT2 has been found to associate with nuclear proteins. Sirtuins have important functions in a diverse yet interrelated set of physiological processes. In this minireview, we discuss research done in the past four years featuring their roles in aging, metabolism, cancer biology, cardiovascular disease, inflammation, and brain pathology. AgingFollowing the first publication describing a role for yeast Sir2 in promoting longevity (2), many laboratories focused on elucidating whether sirtuins might play similar roles in other organisms. Sirtuins have been shown to regulate life span in lower organisms, including yeast, nematodes, and fruit flies (5), although their role in worm and fly life span has recently been debated (6, 7). Most of these studies have described a key role for SIRT1 in regulating the metabolic response to calorie restriction (CR) 5 (8), a dietary intervention that robustly extends life span across numerous species. However, wholebody overexpression of SIRT1 in mice does not affect life span (9). Nevertheless, SIRT1 does appear to promote healthy aging by protecting against several age-related pathologies (10).The strongest link between mammalian sirtuins and the antiaging effects of CR comes from SIRT3, which mediates the prevention of age-related hearing loss by CR (11). Hearing loss is a hallmark of mammalian aging and is characterized by a gradual loss of spiral...

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“…The theory is supported by the observations that over-expressing the mitochondrial antioxidant gene MnSOD [39] or the mitochondrial iron regulator protein frataxin [40] significantly increases longevity in Drosophila, while over-expressing a mitochondriallytargeted catalase gene results in reduced age-related pathology and moderately increased lifespan in mice [41]. Oxidative damage caused by ROS is also postulated to play a role in AHL [4,21,22]. Numerous studies have reported that ROS are generated in the cochlea exposed to noise of an intensity that leads to hearing loss [42,43].…”

Section: Delay Of Age-related Hearing Loss By Crmentioning

confidence: 97%

“…The mechanisms postulated to be responsible for the beneficial effects of CR on aging and AHL include reduced oxidative damage and reduced levels of mtDNA mutations [7][8][9][10][11][12][21][22][23][24][25]. Herein, we review the evidence that CR delays the onset of AHL in laboratory animals.…”

Section: Introductionmentioning

confidence: 99%

Effects of Caloric Restriction on Age-Related Hearing Loss in Rodents and Rhesus Monkeys

Someya¹,

Tanokura²,

Weindruch³

et al. 2010

CAS

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Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is the most frequently occurring sensory disorder in the elderly population. AHL is characterized by a decline of auditory function and loss of hair cells and spiral ganglion neurons in the cochlea of the inner ear. It has been postulated that AHL occurs gradually as a result of the cumulative effect with aging of exposure to noise, diet, oxidative damage, and mitochondrial DNA mutations. However, the molecular mechanisms of AHL remain unclear and no preventative or therapeutic interventions have been developed. A growing body of evidence suggests increased oxidative damage with aging to macromolecules such as DNA, proteins, and lipids may play a causal role in aging and age-related diseases. Caloric restriction (CR) extends the lifespan of most mammalian species, delays the onset of multiple age-related diseases, and attenuates both the degree of oxidative damage and the associated decline in physiological function. Here, we review studies on CR's ability to prevent cochlear pathology and AHL in laboratory animals and discuss potential molecular mechanisms of CR's actions.

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Ageing and hearing loss

Cited by 270 publications

References 63 publications

Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

From Sirtuin Biology to Human Diseases: An Update

Effects of Caloric Restriction on Age-Related Hearing Loss in Rodents and Rhesus Monkeys

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