Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

Madeo, Frank; Carmona-Gutiérrez, Didac; Hofer, Sebastian J.; Kroemer, Guido

doi:10.1016/j.cmet.2019.01.018

Cited by 464 publications

(422 citation statements)

References 224 publications

(256 reference statements)

Supporting

Mentioning

382

Contrasting

Unclassified

Order By: Relevance

“…Due to the difficulties to maintain long-term caloric restriction, the concept of caloric restriction mimicry has been developed (Madeo et al, 2019). The intracellular concentration of spermidine, a natural polyamine and prototype caloric restriction mimetic (CRM), declines during aging, and the administration of spermidine can extend the lifespan of yeast, flies and worms, and human immune cells (Eisenberg et al, 2009).…”

Section: The Role Of Mitophagy In Agingmentioning

confidence: 99%

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Guo

Kroemer

2020

Front. Cell Dev. Biol.

Self Cite

260

159

View full text Add to dashboard Cite

Mitochondrial dysfunction constitutes one of the hallmarks of aging and is characterized by irregular mitochondrial morphology, insufficient ATP production, accumulation of mitochondrial DNA (mtDNA) mutations, increased production of mitochondrial reactive oxygen species (ROS) and the consequent oxidative damage to nucleic acids, proteins and lipids. Mitophagy, a mitochondrial quality control mechanism enabling the degradation of damaged and superfluous mitochondria, prevents such detrimental effects and reinstates cellular homeostasis in response to stress. To date, there is increasing evidence that mitophagy is significantly impaired in several human pathologies including aging and age-related diseases such as neurodegenerative disorders, cardiovascular pathologies and cancer. Therapeutic interventions aiming at the induction of mitophagy may have the potency to ameliorate these dysfunctions. In this review, we summarize recent findings on mechanisms controlling mitophagy and its role in aging and the development of human pathologies.

show abstract

Section: The Role Of Mitophagy In Agingmentioning

confidence: 99%

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Guo

Kroemer

2020

Front. Cell Dev. Biol.

Self Cite

260

159

View full text Add to dashboard Cite

show abstract

“…Complex I is reportedly inhibited by the biguanide antidiabetics metformin and phenformin although doubts can be shed on the capacity of the former to reach concentrations high enough to inhibit OXPHOS in vivo, given the fact that this effect requires millimolar concentrations that cannot be achieved in the clinics. 39 Other complex I inhibitors include carboxyamidotriazole orotate, which is usually considered as an inhibitor of non-voltage-dependent calcium channels, as well as by fenofibrate, a compound used for the treatment of hyperlipidemia. 40 Two low-affinity inhibitors of complex II are known, namely, the vitamin E analogue α-tocopheryl succinate and ionidamine.…”

Section: Strategies For Oxphos Inhibitionmentioning

confidence: 99%

Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Sica

Pedro

Stoll

et al. 2019

Intl Journal of Cancer

Self Cite

152

114

View full text Add to dashboard Cite

In contrast to prior belief, cancer cells require oxidative phosphorylation (OXPHOS) to strive, and exacerbated OXPHOS dependency frequently characterizes cancer stem cells, as well as primary or acquired resistance against chemotherapy or tyrosine kinase inhibitors. A growing arsenal of therapeutic agents is being designed to suppress the transfer of mitochondria from stromal to malignant cells, to interfere with mitochondrial biogenesis, to directly inhibit respiratory chain complexes, or to disrupt mitochondrial function in other ways. For the experimental treatment of cancers, OXPHOS inhibitors can be advantageously combined with tyrosine kinase inhibitors, as well as with other strategies to inhibit glycolysis, thereby causing a lethal energy crisis. Unfortunately, most of the preclinical data arguing in favor of OXPHOS inhibition have been obtained in xenograft models, in which human cancer cells are implanted in immunodeficient mice. Future studies on OXPHOS inhibitors should elaborate optimal treatment schedules and combination regimens that stimulate—or at least are compatible with—anticancer immune responses for long‐term tumor control.

show abstract

“…CR mimetics are compounds that mimic the benefits of CR at the molecular, cellular, and physiological levels, leading to health-promoting effects [100]. Recently, there has been an increased interest in CR mimetics due to the benefits of using these anti-aging interventions in terms of extended health and lifespan [101][102][103]. Although the valuable effects of CR mimetics on lifespan and health have been extensively highlighted, limitations persist because it is difficult to implement such diet regimens in humans.…”

Section: Cr Mimetics In Agingmentioning

confidence: 99%

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

Cited by 464 publications

References 224 publications

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

Contact Info

Product

Resources

About