Metabolic Alterations at the Crossroad of Aging and Oncogenesis

L Raffaghello, V Longo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aging represents the major risk factor for cancer. Cancer and aging are characterized by a similar dysregulated metabolism consisting in upregulation of glycolysis and downmodulation of oxidative phosphorylation. In this respect, metabolic interventions can be viewed as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer. In this review, we discuss the most promising metabolic approaches including chronic calorie restriction, periodic fasting/fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction. Metabolic interventions can also be viewed as adjuvant anticancer strategies to be combined to standard cancer therapy (chemotherapeutic agents, ionizing radiation, and drugs with specific molecular target), whose major limiting factors are represented by toxicity against healthy cells but also limited efficacy easily circumvented by tumor cells. In fact, conventional cancer therapy is unable to distinguish normal and cancerous cells and thus causes toxic side effects including secondary malignancies, cardiovascular and respiratory complications, endocrinopathies, and other chronic conditions, that resemble and, in some cases, accelerate the age-related disorders and profoundly affect the quality of life. In this scenario, geroscience contributes to the understanding of the mechanisms of protection of normal cells against a cytotoxic agent and finding strategies focused on the preserving healthy cells while enhancing the efficacy of the treatment against malignant cells.

Original languageEnglish
Pages (from-to)1-42
Number of pages42
JournalInternational Review of Cell and Molecular Biology
Volume332
DOIs
Publication statusPublished - 2017

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Carcinogenesis
Aging of materials
Cells
Neoplasms
Poisons
Ionizing radiation
Cytotoxins
Nutrition
Metabolism
Toxicity
Tumors
Fasting
Cytoprotection
Oxidative Phosphorylation
Pharmaceutical Preparations
Glycolysis
Ionizing Radiation
Up-Regulation
Quality of Life
Pharmacology

Keywords

  • Journal Article

Cite this

Metabolic Alterations at the Crossroad of Aging and Oncogenesis. / Raffaghello, L; Longo, V.

In: International Review of Cell and Molecular Biology, Vol. 332, 2017, p. 1-42.

Research output: Contribution to journalArticle

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N2 - Aging represents the major risk factor for cancer. Cancer and aging are characterized by a similar dysregulated metabolism consisting in upregulation of glycolysis and downmodulation of oxidative phosphorylation. In this respect, metabolic interventions can be viewed as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer. In this review, we discuss the most promising metabolic approaches including chronic calorie restriction, periodic fasting/fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction. Metabolic interventions can also be viewed as adjuvant anticancer strategies to be combined to standard cancer therapy (chemotherapeutic agents, ionizing radiation, and drugs with specific molecular target), whose major limiting factors are represented by toxicity against healthy cells but also limited efficacy easily circumvented by tumor cells. In fact, conventional cancer therapy is unable to distinguish normal and cancerous cells and thus causes toxic side effects including secondary malignancies, cardiovascular and respiratory complications, endocrinopathies, and other chronic conditions, that resemble and, in some cases, accelerate the age-related disorders and profoundly affect the quality of life. In this scenario, geroscience contributes to the understanding of the mechanisms of protection of normal cells against a cytotoxic agent and finding strategies focused on the preserving healthy cells while enhancing the efficacy of the treatment against malignant cells.

AB - Aging represents the major risk factor for cancer. Cancer and aging are characterized by a similar dysregulated metabolism consisting in upregulation of glycolysis and downmodulation of oxidative phosphorylation. In this respect, metabolic interventions can be viewed as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer. In this review, we discuss the most promising metabolic approaches including chronic calorie restriction, periodic fasting/fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction. Metabolic interventions can also be viewed as adjuvant anticancer strategies to be combined to standard cancer therapy (chemotherapeutic agents, ionizing radiation, and drugs with specific molecular target), whose major limiting factors are represented by toxicity against healthy cells but also limited efficacy easily circumvented by tumor cells. In fact, conventional cancer therapy is unable to distinguish normal and cancerous cells and thus causes toxic side effects including secondary malignancies, cardiovascular and respiratory complications, endocrinopathies, and other chronic conditions, that resemble and, in some cases, accelerate the age-related disorders and profoundly affect the quality of life. In this scenario, geroscience contributes to the understanding of the mechanisms of protection of normal cells against a cytotoxic agent and finding strategies focused on the preserving healthy cells while enhancing the efficacy of the treatment against malignant cells.

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