Senoinflammation: A major mediator underlying age-related metabolic dysregulation.

Chronic inflammation is a complex and unresolved inflammatory response with low-grade multivariable patterns that aggravate systemic pathophysiological conditions and the aging process. To redefine and delineate these age-related complex inflammatory phenomena at the molecular, cellular, and systemic levels, the concept of "Senoinflammation" was recently formulated. In this review, we describe the accumulated data on both the multiphase systemic inflammatory process and the cellular proinflammatory signaling pathway. We also describe the proinflammatory mechanisms underlying the metabolic molecular pathways in aging. Additionally, we review age-related lipid accumulation, the role of the inflammatory senescence-associated secretory phenotype (SASP), the involvement of cytokine/chemokine secretion, endoplasmic reticulum (ER) stress, insulin resistance, and autophagy. The last section of the review highlights the modulation of the senoinflammatory process by the anti-aging and anti-inflammatory action of calorie restriction (CR). Evidence from aging and CR research strongly suggests that SASP from senescent cells may be the major source of secreted cytokines and chemokines during aging. A better understanding of the mechanisms underpinning the senoinflammatory response and the mitigating role of CR will provide insights into the molecular mechanisms of chronic inflammation and aging for potential interventions.