The hallmarks of aging in Ataxia-Telangiectasia

Julio Aguado; Cecilia Gómez-Inclán; Hannah C. Leeson; Martin F. Lavin; Yosef Shiloh; Ernst J. Wolvetang

doi:10.1016/j.arr.2022.101653

The hallmarks of aging in Ataxia-Telangiectasia

Julio Aguado^*, Cecilia Gómez-Inclán, Hannah C. Leeson, Martin F. Lavin, Yosef Shiloh, Ernst J. Wolvetang

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Research output: Contribution to journal › Review article › peer-review

Abstract

Ataxia-telangiectasia (A-T) is caused by absence of the catalytic activity of ATM, a protein kinase that plays a central role in the DNA damage response, many branches of cellular metabolism, redox and mitochondrial homeostasis, and cell cycle regulation. A-T is a complex disorder characterized mainly by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. It is increasingly recognized that the premature aging component of A-T is an important driver of this disease, and A-T is therefore an attractive model to study the aging process. This review outlines the current state of knowledge pertaining to the molecular and cellular signatures of aging in A-T and proposes how these new insights can guide novel therapeutic approaches for A-T.

Original language	English
Article number	101653
Journal	Ageing Research Reviews
Volume	79
DOIs	https://doi.org/10.1016/j.arr.2022.101653
State	Published - Aug 2022

Keywords

ATM
Aging
Ataxia-telangiectasia
Cellular senescence
DNA damage response
Mitochondrial dysfunction
Oxidative stress

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.arr.2022.101653

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title = "The hallmarks of aging in Ataxia-Telangiectasia",

abstract = "Ataxia-telangiectasia (A-T) is caused by absence of the catalytic activity of ATM, a protein kinase that plays a central role in the DNA damage response, many branches of cellular metabolism, redox and mitochondrial homeostasis, and cell cycle regulation. A-T is a complex disorder characterized mainly by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. It is increasingly recognized that the premature aging component of A-T is an important driver of this disease, and A-T is therefore an attractive model to study the aging process. This review outlines the current state of knowledge pertaining to the molecular and cellular signatures of aging in A-T and proposes how these new insights can guide novel therapeutic approaches for A-T.",

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author = "Julio Aguado and Cecilia G{\'o}mez-Incl{\'a}n and Leeson, {Hannah C.} and Lavin, {Martin F.} and Yosef Shiloh and Wolvetang, {Ernst J.}",

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doi = "10.1016/j.arr.2022.101653",

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AU - Aguado, Julio

AU - Gómez-Inclán, Cecilia

AU - Leeson, Hannah C.

AU - Lavin, Martin F.

AU - Shiloh, Yosef

AU - Wolvetang, Ernst J.

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AB - Ataxia-telangiectasia (A-T) is caused by absence of the catalytic activity of ATM, a protein kinase that plays a central role in the DNA damage response, many branches of cellular metabolism, redox and mitochondrial homeostasis, and cell cycle regulation. A-T is a complex disorder characterized mainly by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. It is increasingly recognized that the premature aging component of A-T is an important driver of this disease, and A-T is therefore an attractive model to study the aging process. This review outlines the current state of knowledge pertaining to the molecular and cellular signatures of aging in A-T and proposes how these new insights can guide novel therapeutic approaches for A-T.

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KW - DNA damage response

KW - Mitochondrial dysfunction

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The hallmarks of aging in Ataxia-Telangiectasia

Abstract

Keywords

UN SDGs

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