DNA damage—how and why we age?
Aging is a complex process that results in loss of the ability to reattain homeostasis following stress, leading, thereby, to increased risk of morbidity and mortality. Many factors contribute to aging, such as the time-dependent accumulation of macromolecular damage, including DNA damage. The integ...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/62852 |
| _version_ | 1811200411109949440 |
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| author | Matt Yousefzadeh Chathurika Henpita Rajesh Vyas Carolina Soto-Palma Paul Robbins Laura Niedernhofer |
| author_facet | Matt Yousefzadeh Chathurika Henpita Rajesh Vyas Carolina Soto-Palma Paul Robbins Laura Niedernhofer |
| author_sort | Matt Yousefzadeh |
| collection | DOAJ |
| description | Aging is a complex process that results in loss of the ability to reattain homeostasis following stress, leading, thereby, to increased risk of morbidity and mortality. Many factors contribute to aging, such as the time-dependent accumulation of macromolecular damage, including DNA damage. The integrity of the nuclear genome is essential for cellular, tissue, and organismal health. DNA damage is a constant threat because nucleic acids are chemically unstable under physiological conditions and vulnerable to attack by endogenous and environmental factors. To combat this, all organisms possess highly conserved mechanisms to detect and repair DNA damage. Persistent DNA damage (genotoxic stress) triggers signaling cascades that drive cells into apoptosis or senescence to avoid replicating a damaged genome. The drawback is that these cancer avoidance mechanisms promote aging. Here, we review evidence that DNA damage plays a causal role in aging. We also provide evidence that genotoxic stress is linked to other cellular processes implicated as drivers of aging, including mitochondrial and metabolic dysfunction, altered proteostasis and inflammation. These links between damage to the genetic code and other pillars of aging support the notion that DNA damage could be the root of aging. |
| first_indexed | 2024-04-12T02:04:11Z |
| format | Article |
| id | doaj.art-08d0d6ef18b145da81cb7a7b599d3f46 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:04:11Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-08d0d6ef18b145da81cb7a7b599d3f462022-12-22T03:52:36ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.62852DNA damage—how and why we age?Matt Yousefzadeh0https://orcid.org/0000-0003-2869-1029Chathurika Henpita1https://orcid.org/0000-0002-7610-1380Rajesh Vyas2Carolina Soto-Palma3Paul Robbins4Laura Niedernhofer5https://orcid.org/0000-0002-1074-1385Institute on the Biology of Aging and Metabolism Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United StatesInstitute on the Biology of Aging and Metabolism Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United StatesInstitute on the Biology of Aging and Metabolism Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United StatesInstitute on the Biology of Aging and Metabolism Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United StatesInstitute on the Biology of Aging and Metabolism Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United StatesInstitute on the Biology of Aging and Metabolism Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United StatesAging is a complex process that results in loss of the ability to reattain homeostasis following stress, leading, thereby, to increased risk of morbidity and mortality. Many factors contribute to aging, such as the time-dependent accumulation of macromolecular damage, including DNA damage. The integrity of the nuclear genome is essential for cellular, tissue, and organismal health. DNA damage is a constant threat because nucleic acids are chemically unstable under physiological conditions and vulnerable to attack by endogenous and environmental factors. To combat this, all organisms possess highly conserved mechanisms to detect and repair DNA damage. Persistent DNA damage (genotoxic stress) triggers signaling cascades that drive cells into apoptosis or senescence to avoid replicating a damaged genome. The drawback is that these cancer avoidance mechanisms promote aging. Here, we review evidence that DNA damage plays a causal role in aging. We also provide evidence that genotoxic stress is linked to other cellular processes implicated as drivers of aging, including mitochondrial and metabolic dysfunction, altered proteostasis and inflammation. These links between damage to the genetic code and other pillars of aging support the notion that DNA damage could be the root of aging.https://elifesciences.org/articles/62852DNA damageDNA repairAgingprogeriagenome instability |
| spellingShingle | Matt Yousefzadeh Chathurika Henpita Rajesh Vyas Carolina Soto-Palma Paul Robbins Laura Niedernhofer DNA damage—how and why we age? eLife DNA damage DNA repair Aging progeria genome instability |
| title | DNA damage—how and why we age? |
| title_full | DNA damage—how and why we age? |
| title_fullStr | DNA damage—how and why we age? |
| title_full_unstemmed | DNA damage—how and why we age? |
| title_short | DNA damage—how and why we age? |
| title_sort | dna damage how and why we age |
| topic | DNA damage DNA repair Aging progeria genome instability |
| url | https://elifesciences.org/articles/62852 |
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