Abstract
Aging increases the risk of cancer partly through alterations in the tissue microenvironment. Time-restricted feeding (TRF) is being proposed as an effective strategy to delay biological aging. In the present studies, we assessed the effect of long-term exposure to TRF on the emergence of the age-associated, neoplastic-prone tissue landscape. Animals were exposed to either ad libitum feeding (ALF) or TRF for 18 months and then transplanted with hepatocytes isolated from pre-neoplastic nodules. Both groups were continued ALF and the growth of transplanted cells was evaluated 3 months later. A significant decrease in frequency of larger size clusters of pre-neoplastic hepatocytes was seen in TRF-exposed group compared to controls. Furthermore, TRF modified several parameters related to both liver and systemic aging towards the persistence of a younger phenotype, including a decrease in liver cell senescence, diminished fat accumulation and up-regulation of SIRT1 in the liver, down-regulation of plasma IGF-1, decreased levels of plasma lipoproteins and up-regulation of hippocampal brain-derived growth factor (BDNF).These results indicate that TRF was able to delay the onset of the neoplastic-prone tissue landscape typical of aging. To our knowledge, this is the first investigation to describe a direct beneficial effect of TRF on early phases of carcinogenesis.
Highlights
The link between aging and neoplastic disease is widely acknowledged
Animals were assigned to Time-restricted feeding (TRF) or ad libitum feeding (ALF) group at 8 weeks of age and they were maintained on their respective dietary regimens for 18 months (Figure 1A)
The results of the present studies indicate that long-term exposure to TRF retards the onset of the clonogenic and neoplastic-prone hepatic tissue microenvironment associated with aging
Summary
The link between aging and neoplastic disease is widely acknowledged. In addition, it is increasingly apparent that some of the most relevant risk factors for cancer in humans are associated with signs of accelerated aging in their target organ. Examples include smoking for the respiratory mucosa, chronic hepatitis for the liver, UV light for the skin, chronic (atrophic) gastritis for the stomach, among others [1,2,3,4,5,6,7] This underscores the argument that the pathophysiology of aging is strictly intertwined with that of carcinogenesis, to the point that the emergence of the aged phenotype stands as a major biological driving force towards neoplastic development. In a more recent report, exposure to TRF for 8 weeks was found to mitigate high-fat diet-enhanced mammary tumorigenesis in the mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) model [25] Based on these premises, the present investigation analyzes the effect of long term TRF on the emergence of the age-associated, neoplastic-prone tissue microenvironment in rat liver. The possible effect of TRF on liver specific and systemic, age-related phenotypic alterations is addressed
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