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.

Healthy Aging Interventions Reduce Repetitive Element Transcripts

“…Furthermore, we found that both long-term (8 months) rapamycin and acarbose treatments were associated with a comparable, broad reduction in RE transcripts (Fig. 1B), consistent with the notion that these compounds are 'calorie restriction mimetics' and may act via similar pathways (17). This effect was particularly clear when we examined RE/TE reductions by major sub-type (Fig.…”

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

“…Calorie restriction is one of the most promising approaches for reducing the negative effects of metabolic disorders, age-related diseases, and pathologies associated with metaflammation ( Park et al, 2012 ; Ma et al, 2020 ). In animal studies, it has been shown that reducing calorie intake increases life span and helps to lower blood glucose and insulin levels ( Redman and Ravussin, 2011 ; Kim et al, 2020 ). There is currently evidence that CR for 2 years by 15% in healthy, non-obese people leads to a decrease in systemic oxidative damage ( Redman et al, 2018 ).…”

Does Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors?

“…Chronic, sterile, low-level inflammation has been considered as a factor that accelerates the aging process, which is referred to as “inflammaging” [ 9 , 17 ] or “senoinflammation” [ 15 ]. This persistent low-level inflammation conferring toxic insults on tissues not only accelerates aging but also causes aging-related diseases.…”

“…CR is reported to effectively reduce circulating inflammatory signatures that are induced by aging or obesity [ 55 , 56 , 57 ]. The molecular mechanisms by which CR affects aging and related diseases are well reviewed elsewhere under the concept of “senoinflammation” [ 15 ]. Several studies have already indicated the inhibitory effect of CR on the aging-related increase of inflammation.…”

“…This relative activation of innate immunity results in the propagation of inflammatory responses, leading to chronic low-level inflammatory phenotypes in aging tissue [ 9 , 14 ]. This is also referred to as senoinflammation [ 15 ].…”