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

Nutrients. 2020;12(2)

Plain language summary

Low grade, systemic, chronic inflammation is a feature of ageing and underlies many age-related chronic diseases states. As cells age their capacity to proliferate declines, which is referred to as cell senescence. Such senescent cells release multiple inflammatory markers contributing to a pro-inflammatory state. This is further aggravated by elevated oxidative stress and a reduced capacity to manage it, eventually leading to improper gene regulation and DNA damage. To define this age-related, complex inflammatory phenomena the authors introduced the term senoinflammation. A well-established intervention to reverse or slow down the ageing process and many ageing-associated diseases is calorie restriction (CR), by means of reducing overall caloric intake without malnutrition. CR exhibits potent anti-inflammatory effects, reduces age-associated oxidative stress, improves age-related metabolic dysregulation and enhances favourable gene expression. This review summarises how CR and CR-mimicking substances exert their anti-inflammatory effect and some of the cellular mechanism involved and may be of interest to those who are looking to get a more detailed understanding on ageing, inflammation and the benefits of CR.


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.

Lifestyle medicine

Fundamental Clinical Imbalances : Immune and inflammation
Patient Centred Factors : Mediators/Chronic inflammation
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition ; Environment
Functional Laboratory Testing : Not applicable

Methodological quality

Jadad score : Not applicable
Allocation concealment : Not applicable
Publication Type : Journal Article ; Review