Researchers: Jordan J Baechle, Nan Chen, Priya Makhijani, Shawn Winer, David Furman, Daniel A Winer
BACKGROUND: Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as “inflammaging,” which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty. How the crosstalk between chronic inflammation and other hallmarks of aging underlies biological mechanisms of aging and age-related disease is thus of particular interest to the current geroscience research. SCOPE OF REVIEW: This review integrates the cellular and molecular mechanisms of age-associated chronic inflammation with the other eleven hallmarks of aging. Extra discussion is dedicated to the hallmark of “altered nutrient sensing,” given the scope of Molecular Metabolism. The deregulation of hallmark processes during aging disrupts the delicate balance between pro-inflammatory and anti-inflammatory signaling, leading to a persistent inflammatory state. The resultant chronic inflammation, in turn, further aggravates the dysfunction of each hallmark, thereby driving the progression of aging and age-related diseases. MAIN CONCLUSIONS: The crosstalk between chronic inflammation and other hallmarks of aging results in a vicious cycle that exacerbates the decline in cellular functions and promotes aging. Understanding this complex interplay will provide new insights into the mechanisms of aging and the development of potential anti-aging interventions. Given their interconnectedness and ability to accentuate the primary elements of aging, drivers of chronic inflammation may be an ideal target with high translational potential to address the pathological conditions associated with aging.
References
- The hallmarks of aging.
- Immunology of Aging: the Birth of Inflammaging.
- Connecting aging biology and inflammation in the omics era.
- DNA damage and repair in age-related inflammation.
- The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.
- New Insights into the Genetics and Epigenetics of Aging Plasticity.
- Epigenetic regulation of aging: implications for interventions of aging and diseases.
- The Role of Immune Cells in Oxi-Inflamm-Aging.
- Autophagy in healthy aging and disease.
- Cellular senescence and senolytics: the path to the clinic.
- mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity.
- Key proteins and pathways that regulate lifespan.
- Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan.
- Why Is Longevity Still a Scientific Mystery? Sirtuins-Past, Present and Future.
- Downregulation of Sirt6 by CD38 promotes cell senescence and aging.
- Targeting cellular senescence in metabolic disease.
- A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues.
- COVID-19 and cellular senescence.
- Aging and aging-related diseases: from molecular mechanisms to interventions and treatments.
- Ageing and rejuvenation of tissue stem cells and their niches.
- Loss of epigenetic information as a cause of mammalian aging.
- The Gut Microbiome, Aging, and Longevity: A Systematic Review.