Epigenetic Changes in Aging and Age-related Disease

Rowbotham, David A.

doi:10.4172/2329-8847.1000130

Cited by 7 publications

(4 citation statements)

References 172 publications

(187 reference statements)

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“…Since almost all living organisms contain a multitude of viruses which modify the host and evolve at a greater pace than the host genome [ 38 – 41 ], there can be no genetic program for handling all the possible scenarios of maladaptive conditions. A similar limitation applies to coping with individual-specific epigenetic drifts associated with aging [ 42 – 44 ] and recovering from other types of individual-specific lesions (e.g. microinfarcts in various tissues [ 45 , 46 ]).…”

Section: Hypothesismentioning

confidence: 99%

A principle of organization which facilitates broad Lamarckian-like adaptations by improvisation

2015

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BackgroundDuring the lifetime of an organism, every individual encounters many combinations of diverse changes in the somatic genome, epigenome and microbiome. This gives rise to many novel combinations of internal failures which are unique to each individual. How any individual can tolerate this high load of new, individual-specific scenarios of failure is not clear. While stress-induced plasticity and hidden variation have been proposed as potential mechanisms of tolerance, the main conceptual problem remains unaddressed, namely: how largely non-beneficial random variation can be rapidly and safely organized into net benefits to every individual.Presentation of the hypothesisWe propose an organizational principle which explains how every individual can alleviate a high load of novel stressful scenarios using many random variations in flexible and inherently less harmful traits. Random changes which happen to reduce stress, benefit the organism and decrease the drive for additional changes. This adaptation (termed ‘Adaptive Improvisation’) can be further enhanced, propagated, stabilized and memorized when beneficial changes reinforce themselves by auto-regulatory mechanisms. This principle implicates stress not only in driving diverse variations in cells tissues and organs, but also in organizing these variations into adaptive outcomes. Specific (but not exclusive) examples include stress reduction by rapid exchange of mobile genetic elements (or exosomes) in unicellular, and rapid changes in the symbiotic microorganisms of animals. In all cases, adaptive changes can be transmitted across generations, allowing rapid improvement and assimilation in a few generations.Testing the hypothesisWe provide testable predictions derived from the hypothesis.Implications of the hypothesisThe hypothesis raises a critical, but thus far overlooked adaptation problem and explains how random variation can self-organize to confer a wide range of individual-specific adaptations beyond the existing outcomes of natural selection. It portrays gene regulation as an inseparable synergy between natural selection and adaptation by improvisation. The latter provides a basis for Lamarckian adaptation that is not limited to a specific mechanism and readily accounts for the remarkable resistance of tumors to treatment.ReviewersThis article was reviewed by Eugene V. Koonin, Yuri Wolf and Itai Yanai.

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Section: Hypothesismentioning

confidence: 99%

A principle of organization which facilitates broad Lamarckian-like adaptations by improvisation

2015

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“…Genomic instability, aberrant gene expression, and the loss in chromatin structure are features of both aging and multifactorial diseases such as AD [76,77]. These alterations are intimately associated to epigenomic changes [78], and can be responsive to environmental influence [79]. Aging represents the main risk factor for AD and most tauopathies, hence, age-associated epigenetic alterations likely contribute to the structural and functional changes of the brain that lead to progressive cognitive deficits and possibly derived augmented susceptibility to neurodegenerative disorders such as AD and tauopathies [80,81].…”

Section: Age-dependent Changes Of Dna Methylation Marks and The Relevance For Ad And Tauopathiesmentioning

confidence: 99%

DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons from Alzheimer’s, Related Tauopathies and Genetic Tauopathies

Zimmer-Bensch

Zempel

2021

Cells

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Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in the case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here, we review current knowledge of tauopathies listing known genetic and important sporadic forms of these disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tools and usages of epigenetic therapy strategies for these diseases.

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“…Aberrant gene expression, genomic instability, and the loss in chromatin structure are features of both aging and multifactorial or complex diseases such as AD [64,65]. These alterations are intimately associated to changes in the epigenome [66], and can be responsive to environmental influence [67]. As aging represents the main risk factor for AD and most tauopathies, it is conceivable that the epigenetic changes coming along with the aging process that affect brain function predispose for or are associated with AD and tauopathies.…”

Section: Age-dependent Changes Of Dna Methylation Signatures and The Relevance For Ad And Tauopathiesmentioning

confidence: 99%

DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons From Alzheimers, Related Tauopathies and Genetic Tauopathies

Zimmer-Bensch¹,

Zempel²

2021

Preprint

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Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

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Epigenetic Changes in Aging and Age-related Disease

Cited by 7 publications

References 172 publications

A principle of organization which facilitates broad Lamarckian-like adaptations by improvisation

A principle of organization which facilitates broad Lamarckian-like adaptations by improvisation

DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons from Alzheimer’s, Related Tauopathies and Genetic Tauopathies

DNA Methylation in Genetic and Sporadic Forms of Neurodegeneration: Lessons From Alzheimers, Related Tauopathies and Genetic Tauopathies

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