Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan

Abstract

Caloric restriction (CR), the reduction of caloric intake without inducing malnutrition, is the most reproducible method of extending health and lifespan across numerous organisms, including humans. However, with nearly one-third of the world’s population overweight, it is obvious that caloric restriction approaches are difficult for individuals to achieve. Therefore, identifying compounds that mimic CR is desirable to promote longer, healthier lifespans without the rigors of restricting diet. Many compounds, such as rapamycin (and its derivatives), metformin, or other naturally occurring products in our diets (nutraceuticals), induce CR-like states in laboratory models. An alternative to CR is the removal of specific elements (such as individual amino acids) from the diet. Despite our increasing knowledge of the multitude of CR approaches and CR mimetics, the extent to which these strategies overlap mechanistically remains unclear. Here we provide an update of CR and CR mimetic research, summarizing mechanisms by which these strategies influence genome function required to treat age-related pathologies and identify the molecular fountain of youth.

Haskap Berry Phenolic Subclasses Differentially Impact Cellular Stress Sensing in Primary and Immortalized Dermal Fibroblasts

“…Sirtuin1 is a deacetylase enzyme targeting several proteins/pathways, including those involved with mediating cellular stress and promoting cellular and organismal lifespan such as NF-κB, mTOR and NRF2 [31]. Several phenolics [32][33][34][35], including resveratrol [36][37][38], have been reported to influence SIRT1 protein levels.…”

Altered immunometabolism in adipose tissue: A major contributor to the ageing process?

“…Notably, a pro‐inflammatory adipose tissue secretory profile is a characteristic of cellular senescence (cellular ageing), the accumulation of which is associated with many age‐related diseases (Almendáriz‐Palacios et al . 2020). Furthermore, it is known that the secretion of pro‐inflammatory proteins further induces senescence in surrounding cells, which propagates the systematic ageing process (Almendáriz‐Palacios et al .…”

“…Furthermore, it is known that the secretion of pro‐inflammatory proteins further induces senescence in surrounding cells, which propagates the systematic ageing process (Almendáriz‐Palacios et al . 2020). Unexpectedly, adiponectin, a hormone considered as an anti‐inflammatory in nature, was increased in the circulation of older individuals compared to young.…”

“…It has been extensively documented that insulin sensitivity and insulin‐like growth factor‐1 decrease with age, contributing to metabolic and age‐associated diseases (Almendáriz‐Palacios et al . 2020). Trim et al .…”

“…It has been extensively documented that insulin sensitivity and insulin-like growth factor-1 decrease with age, contributing to metabolic and age-associated diseases (Almendáriz-Palacios et al 2020). Trim J Physiol 600.4 et al (2021 examined some key proteins involved in insulin signalling pathways and identified lower levels of glucose transporters and insulin receptors in the aged adipose tissue, but not in the skeletal muscle.…”