Molecular Damage in Aging
Vadim N Gladyshev1, Stephen B Kritchevsky2, Steven G Clarke3,4
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Cellular metabolism generates molecular damage affecting all levels of biological organization. Accumulation of this damage over time is thought to play a central role in the aging process, but damage manifests in diverse molecular forms complicating its assessment. Insufficient attention has been paid to date to the role of molecular damage in aging-related phenotypes, particularly in humans, in part because of the difficulty in measuring its various forms. Recently, omics approaches have been developed that begin to address this challenge, because they are able to assess a sizeable proportion of age-related damage at the level of small molecules, proteins, RNA, DNA, organelles and cells. This review describes the concept of molecular damage in aging and discusses its diverse aspects from theoretical models to experimental approaches. Measurement of multiple types of damage enables studies of the role of damage in human aging outcomes and lays a foundation for testing interventions to reduce the burden of molecular damage, opening new approaches to slowing aging and reducing its consequences.
Insights
Cellular metabolism causes molecular damage, a key factor in aging. New omics methods can measure this damage, aiding research into human aging and interventions to slow it.
Area of Science:
- Gerontology and molecular biology.
- Focuses on the molecular underpinnings of the aging process.
Background:
- Cellular metabolism inherently produces molecular damage.
- Accumulated damage is a primary driver of aging phenotypes.
- Assessing diverse molecular damage forms in humans has been challenging.
Approach:
- Omics technologies offer a comprehensive approach to measure age-related molecular damage.
- These methods assess damage across various biological levels: small molecules, proteins, RNA, DNA, organelles, and cells.
- The review synthesizes theoretical models and experimental strategies for damage assessment.
Key Points:
- Molecular damage manifests in diverse forms, complicating aging research.
- Omics approaches enable large-scale assessment of age-related molecular damage.
- Understanding damage is crucial for studying human aging outcomes.
Conclusions:
- Measuring diverse molecular damage is essential for understanding human aging.
- This forms a basis for developing interventions to mitigate aging.
- New strategies can potentially slow aging and reduce its associated health consequences.
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