Nutrition in Cancer Therapy in the Elderly-An Epigenetic Connection?

Abstract

The continuous increase in life expectancy results in a steady increase of cancer risk, which consequently increases the population of older adults with cancer. Older adults have their age-related nutritional needs and often suffer from comorbidities that may affect cancer therapy. They frequently are malnourished and present advanced-stage cancer. Therefore, this group of patients requires a special multidisciplinary approach to optimize their therapy and increase quality of life impaired by aging, cancer, and the side effects of therapy. Evaluation strategies, taking advantage of comprehensive geriatric assessment tools, including the comprehensive geriatric assessment (CGA), can help individualize treatment. As epigenetics, an emerging element of the regulation of gene expression, is involved in both aging and cancer and the epigenetic profile can be modulated by the diet, it seems to be a candidate to assist with planning a nutritional intervention in elderly populations with cancer. In this review, we present problems associated with the diet and nutrition in the elderly undergoing active cancer therapy and provide some information on epigenetic aspects of aging and cancer transformation. Nutritional interventions modulating the epigenetic profile, including caloric restriction and basal diet with modifications (elimination diet, supplementary diet) are discussed as the ways to improve the efficacy of cancer therapy and maintain the quality of life of older adults with cancer.

Keywords: DNA methylation; caloric restriction; cancer; epigenetic diet; epigenetic regulation of gene expression; malnutrition; nutrition; older adults.

Figure 1

Main factors affecting therapy in older adults with cancer. Some of these factors are mutually dependent and some partly overlap. Environment is understood here in a broad sense and also includes family and social relationships. Some factors, such as the diet, are of general significance, but have several features specific for this group of patients.

Figure 2

Comprehensive geriatric assessment (CGA) is an organized evaluation method to provide a multidisciplinary assessment of and care for the elderly. It assesses physical medical conditions, including comorbidity, the disease severity, immunization status, and others. Assessment of functional status refers to an elderly person’s ability to perform daily tasks and determines several core functions, including balance and mobility. Other areas of CGA include issues contained in broad categories of assessment of social health and environment.

Figure 3

The interplay between genetic and epigenetic factors in cancer transformation. Genomic instability, typical for most cancers, results in an increased number of mutations in genes encoding modifiers of the epigenetic profile. On the other hand, epigenetic changes, including DNA methylation, histone modification, and changes in non-coding RNAs, affect the expression of genes responsible for the maintenance of DNA, resulting in an increased number of chromosomal aberrations, DNA point mutations, amplifications, and other changes increasing genome instability.

Figure 4

The crosstalk between epigenetic changes, transcription, and genomic instability. In a young organism, transcription is fully controlled and produced the same amount of mRNA in the cells that activate the same genes. In these cells, normal chromatin state and genomic stability are maintained. With increased age, genomic instability increases, resulting in gene mutations and chromosomal aberrations and unstable transcription. Increased DNA damage may result in DNA damage response inducing the recruitment of epigenetic modifiers of chromatin structure and locally resuming its conformation, which may partly stabilize the transcription of neighboring genes. Epimutations, which accumulate in later life, may hamper this process.