Aging promotes neoplastic disease through effects on the tissue microenvironment

Marongiu, Fabio; Serra, Maria Paola; Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Mauro; Laconi, Ezio

doi:10.18632/aging.101128

Cited by 22 publications

(33 citation statements)

References 41 publications

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“…109 As demonstrated by various studies performed in murine models, the expression of senescence markers in the liver create a microenvironment that promotes cancer development. 110,111 Indeed, age-related alterations support the selective growth of both preneoplastic cell populations and normal, homotypical transplanted cells. 112 This suggests that there are similar mechanisms behind the growth of both cell types, which could represent a therapeutic target in the treatment of neoplasms.…”

Section: Aging-related Molecular Alterations In Liver Diseasesmentioning

confidence: 99%

Aging and the Biological Response to Liver Injury

et al. 2019

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Interest in understanding the aging process has recently risen in the scientific community. Aging, commonly defined as the functional decline in the function of organs and tissues, is indeed the major risk factor for the development of many chronic diseases, such as cardiovascular diseases, pathologies of nervous system, or cancer. To date, the influence of aging in the pathophysiology of liver and biliary diseases is not fully understood. Although liver cells have a high regenerative capacity, hepatocytes and cholangiocytes undergo extensive molecular changes in response to aging. Following time-dependent damage induced by aging, liver cells initially activate compensatory mechanisms that, if hyperstimulated, may lead to the decline of regenerative capacity and the development of pathologies. A deeper understanding of molecular aging has undoubtedly the potential to improve the clinical management of patients, possibly unveiling new pathways for selective drug treatment.

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Section: Aging-related Molecular Alterations In Liver Diseasesmentioning

confidence: 99%

Aging and the Biological Response to Liver Injury

et al. 2019

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“…In this work, we investigated whether fecal microbiota variation is induced by short-term CR and whether such change persists in long-lasting CR, in a rat model of aging. 8 As for the majority of murine experimental models, animals were fed AL, a condition that might be assimilated to overfeeding, given the poor energy expenditure in the animal house settings, compared to wild rats in their natural environments. 9 To shed light on timing and nature of microbial composition changes, fecal microbiota was evaluated in young growing and adult Fisher 344 rats, comparing animals fed AL and animals fed with 70% of the AL ratio (CR).…”

Section: Introductionmentioning

confidence: 99%

Caloric restriction promotes rapid expansion and long-lasting increase of Lactobacillus in the rat fecal microbiota

et al. 2017

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Previous studies indicated that caloric restricted diet enables to lower significantly the risk of cardiovascular and metabolic diseases. In experimental animal models, life-long lasting caloric restriction (CR) was demonstrated to induce changes of the intestinal microbiota composition, regardless of fat content and/or exercise. To explore the potential impact of short and long-term CR treatment on the gut microbiota, we conducted an analysis of fecal microbiota composition in young and adult Fisher 344 rats treated with a low fat feed under ad libitum (AL) or CR conditions (70%). We report here significant changes of the rat fecal microbiota that arise rapidly in young growing animals after short-term administration of a CR diet. In particular, Lactobacillus increased significantly after 8 weeks of CR treatment and its relative abundance was significantly higher in CR vs AL fed animals after 36 weeks of dietary intervention. Taken together, our data suggest that Lactobacillus intestinal colonization is hampered in AL fed young rats compared to CR fed ones, while health-promoting CR diet intervention enables the expansion of this genus rapidly and persistently up to adulthood.

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“…This hypothesis was also grounded on our recent report describing the promoting capability of an aged tissue-microenvironment on the growth of pre-neoplastic hepatocytes [3]. Two groups of rats were fed either AL or a CR diet for 17 months, starting at 8 weeks of age and they were then transplanted with pre-neoplastic hepatocytes.…”

Section: Discussionmentioning

confidence: 91%

“…Hepatocyte nodules were induced according to a well characterized experimental model in the rat [3]. Briefly, two-month old male Fischer 344 DPPIV+ rats were injected with a single dose of diethylnitrosamine (DENA, 200 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

Caloric restriction delays early phases of carcinogenesis via effects on the tissue microenvironment

et al. 2017

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Caloric restriction (CR) is an effective and consistent means to delay aging and the incidence of chronic diseases related to old age, including cancer. However, the precise mechanisms responsible for the beneficial effect of CR on carcinogenic process are yet to be identified.In the present studies the hypothesis was tested that the CR might delay carcinogenesis via modulatory effects exerted on the age-associated, neoplastic-prone tissue microenvironment. Using a well characterized, orthotopic cell transplantation (Tx) system in the rat, preneoplastic hepatocytes isolated from liver nodules were injected into either old syngeneic rats fed ad libitum (AL) or animals of the same age given a CR diet (70% of AL feeding). Analysis of donor-derived cell clusters performed at 10 weeks post-Tx revealed a significant shift towards smaller class sizes in the group receiving CR diet. Clusters comprising more than 50 cells, including large hepatic nodules, were thrice more frequent in AL vs. CR animals. Incidence of spontaneous endogenous nodules was also decreased by CR. Markers of cell senescence were equally expressed in the liver of AL and CR groups. However, higher levels of SIRT1 and FOXO1 proteins were detected in CR-exposed livers, while expression of HDAC1 and C/EBPβ were decreased. These results are interpreted to indicate that CR delays the emergence of age-associated neoplastic disease through effects exerted, at least in part, on the tissue microenvironment. Nutrient-sensing pathways might mediate such modulatory effect.

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Aging promotes neoplastic disease through effects on the tissue microenvironment

Cited by 22 publications

References 41 publications

Aging and the Biological Response to Liver Injury

Aging and the Biological Response to Liver Injury

Caloric restriction promotes rapid expansion and long-lasting increase of Lactobacillus in the rat fecal microbiota

Caloric restriction delays early phases of carcinogenesis via effects on the tissue microenvironment

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