Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept

Abstract

Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.

Keywords: aging; calorie restriction; mimetics; senescence-associated secretory phenotype; senoinflammation.

Figure 1

Possible mechanism of senoinflammation in aging. During aging, the continuous age-related inflammatory responses that cause metabolic dysregulation to form a vicious cycle. Age-related inflammation and metabolic dysregulation result in the induction and activation of many pro-inflammatory genes, metabolic and signaling pathways, and SASP. This vicious cycle of age-related chronic inflammation and metabolic dysregulation underlies the senoinflammation phenomenon, which occurs because of the interaction between senescent cells, immune cells, adipocytes, hepatocytes, and myocytes. SASP, senescence associated secretory phenotype; CR, calorie restriction.