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Published on: June 28, 2019
Cellular senescence in age-related disorders
1Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester Minnesota; Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic, Rochester Minnesota.
Abstract:
Much of the population is now faced with an enormous burden of age-associated chronic diseases. Recent discoveries in geroscience indicate that healthspan in model organisms such as mice can be manipulated by targeting cellular senescence, a hallmark mechanism of aging, defined as an irreversible proliferative arrest that occurs when cells experience oncogenic or other diverse forms of damage. Senescent cells and their proinflammatory secretome have emerged as contributors to age-related tissue dysfunction and morbidity. Cellular senescence has causal roles in mediating osteoporosis, frailty, cardiovascular diseases, osteoarthritis, pulmonary fibrosis, renal diseases, neurodegenerative diseases, hepatic steatosis, and metabolic dysfunction. Therapeutically targeting senescent cells in mice can prevent, delay, or alleviate each of these conditions. Therefore, senotherapeutic approaches, including senolytics and senomorphics, that either selectively eliminate senescent cells or interfere with their ability to promote tissue dysfunction, are gaining momentum as potential realistic strategies to abrogate human senescence to thereby compress morbidity and extend healthspan.
Insights
Cellular senescence, a key aging mechanism, drives chronic diseases. Targeting senescent cells with senotherapeutics shows promise for extending healthspan and reducing age-related illness.
Area of Science:
- Geroscience
- Cellular and Molecular Biology
- Aging Research
Background:
- Aging is associated with a significant burden of chronic diseases.
- Cellular senescence, a state of irreversible cell cycle arrest, is a hallmark of aging.
- Senescent cells and their secreted factors contribute to age-related tissue dysfunction and disease.
Purpose of the Study:
- To explore the role of cellular senescence in age-associated chronic diseases.
- To evaluate the therapeutic potential of targeting senescent cells for healthspan extension.
Main Methods:
- Review of geroscience discoveries and studies in model organisms.
- Analysis of the impact of senescent cells on various age-related conditions.
- Examination of senotherapeutic strategies, including senolytics and senomorphics.
Main Results:
- Cellular senescence is implicated in numerous age-related diseases, including osteoporosis, cardiovascular disease, and neurodegeneration.
- Therapeutic elimination or modulation of senescent cells in mice can prevent or alleviate these conditions.
- Senotherapeutic approaches demonstrate potential for compressing morbidity.
Conclusions:
- Targeting cellular senescence is a viable strategy to combat age-associated chronic diseases.
- Senolytics and senomorphics offer promising avenues for extending human healthspan and reducing disease burden.
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