Chronic inflammation and the hallmarks of aging

Jordan J Baechle; Nan Chen; Priya Makhijani; Shawn Winer; David Furman; Daniel A Winer

doi:10.1016/j.molmet.2023.101755

Chronic inflammation and the hallmarks of aging

Mol Metab. 2023 Aug:74:101755. doi: 10.1016/j.molmet.2023.101755. Epub 2023 Jun 15.

Authors

Jordan J Baechle¹, Nan Chen², Priya Makhijani³, Shawn Winer⁴, David Furman⁵, Daniel A Winer⁶

Affiliations

¹ Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA.
² Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, Canada.
³ Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁵ Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA; Stanford 1000 Immunomes Project, Stanford University School of Medicine, Stanford, CA, USA; Instituto de Investigaciones en Medicina Traslacional (IIMT), Universidad Austral, CONICET, Pilar, Argentina. Electronic address: DFurman@buckinstitute.org.
⁶ Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, Canada; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA. Electronic address: DWiner@buckinstitute.org.

Abstract

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.

Keywords: Ageing; Aging; Inflammaging; Inflammation; Nutrient sensing; Senescence.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Aged
Anti-Inflammatory Agents
Cardiovascular Diseases*
Humans
Inflammation*

Substances

Anti-Inflammatory Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding