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. 2022 Oct;61(7):3391-3406.
doi: 10.1007/s00394-022-02893-0. Epub 2022 May 5.

The influence of association between aging and reduced protein intake on some immunomodulatory aspects of bone marrow mesenchymal stem cells: an experimental study

Renaira Oliveira da Silva  1 , Araceli Aparecida Hastreiter  1 , Gabriela Kodja Vivian  1 , Carolina Carvalho Dias  1 , Andressa Cristina Antunes Santos  1 , Edson Naoto Makiyama  1 , Primavera Borelli  1 , Ricardo Ambrósio Fock  2
Affiliations

The influence of association between aging and reduced protein intake on some immunomodulatory aspects of bone marrow mesenchymal stem cells: an experimental study

Renaira Oliveira da Silva et al. Eur J Nutr. 2022 Oct.

Abstract

Purpose: Dietary protein deficiency is common in the elderly, compromising hematopoiesis and the immune response, and may cause a greater susceptibility to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are essential to hematopoiesis. Therefore, this study aimed to investigate, in an aging model subjected to malnutrition due a reduced protein intake, aspects related to the immunomodulatory capacity of MSCs.

Methods: Male C57BL/6 mice from young and elderly groups were fed with normoproteic or hypoproteic diets (12% and 2% of protein, respectively) and nutritional, biochemical and hematological parameters were evaluated. MSCs from bone marrow were isolated, characterized and their secretory parameters evaluated, along with gene expression. Additionally, the effects of aging and protein malnutrition on MSC immunomodulatory properties were assessed.

Results: Malnourished mice lost weight and demonstrated anemia, leukopenia, and bone marrow hypoplasia. MSCs from elderly animals from both groups showed reduced CD73 expression and higher senescence rate; also, the malnourished state affected CD73 expression in young animals. The production of IL-1β and IL-6 by MSCs was affected by aging and malnutrition, but the IL-10 production not. Aging also increased the expression of NFκB, reducing the expression of STAT-3. However, MSCs from malnourished groups, regardless of age, showed decreased TGF-β and PGE2 production. Evaluation of the immunomodulatory capacity of MSCs revealed that aging and malnutrition affected, mainly in lymphocytes, the production of IFN-γ and IL-10.

Conclusion: Aging and reduced protein intake are factors that, alone or together, influence the immunomodulatory properties of MSCs and provide basic knowledge that can be further investigated to explore whether MSCs' therapeutic potential may be affected.

Keywords: Aging; Cytokines; Mesenchymal stem cell; Protein malnutrition.

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