bims-minfam 2023-04-02 papers

Issue of 2023–04–02
three papers selected by
Ayesh Seneviratne, Western University

Int J Mol Sci. 2023 Mar 20. pii: 5862. [Epub ahead of print]24(6):

Hematopoietic Stem Cells and the Immune System in Development and Aging.

Daniil Shevyrev, Valeriy Tereshchenko, Tatiana N Berezina, Stanislav Rybtsov.

Hematopoietic stem cells (HSCs) support haematopoiesis throughout life and give rise to the whole variety of cells of the immune system. Developing in the early embryo, passing through the precursor stage, and maturing into the first HSCs, they undergo a fairly large number of divisions while maintaining a high regenerative potential due to high repair activity. This potential is greatly reduced in adult HSCs. They go into a state of dormancy and anaerobic metabolism to maintain their stemness throughout life. However, with age, changes occur in the pool of HSCs that negatively affect haematopoiesis and the effectiveness of immunity. Niche aging and accumulation of mutations with age reduces the ability of HSCs to self-renew and changes their differentiation potential. This is accompanied by a decrease in clonal diversity and a disturbance of lymphopoiesis (decrease in the formation of naive T- and B-cells) and the predominance of myeloid haematopoiesis. Aging also affects mature cells, regardless of HSC, therefore, phagocytic activity and the intensity of the oxidative burst decrease, and the efficiency of processing and presentation of antigens by myeloid cells is impaired. Aging cells of innate and adaptive immunity produce factors that form a chronic inflammatory background. All these processes have a serious negative impact on the protective properties of the immune system, increasing inflammation, the risk of developing autoimmune, oncological, and cardiovascular diseases with age. Understanding the mechanisms of reducing the regenerative potential in a comparative analysis of embryonic and aging HSCs, the features of inflammatory aging will allow us to get closer to deciphering the programs for the development, aging, regeneration and rejuvenation of HSCs and the immune system.

Keywords: HSC; HSC precursors; aging; aging biomarkers; haematopoietic clonality; haematopoietic hierarchy; hematopoietic stem cells; immune aging; immune senescence; inflammation; pre-HSC

DOI: https://doi.org/10.3390/ijms24065862

Int J Mol Sci. 2023 Mar 14. pii: 5508. [Epub ahead of print]24(6):

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks.

Quélita Cristina Pereira, Tanila Wood Dos Santos, Isabela Monique Fortunato, Marcelo Lima Ribeiro.

Ageing is a complex process characterized mainly by a decline in the function of cells, tissues, and organs, resulting in an increased risk of mortality. This process involves several changes, described as hallmarks of ageing, which include genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and altered intracellular communication. The determining role that environmental factors such as diet and lifestyle play on health, life expectancy, and susceptibility to diseases, including cancer and neurodegenerative diseases, is wellestablished. In view of the growing interest in the beneficial effects of phytochemicals in the prevention of chronic diseases, several studies have been conducted, and they strongly suggest that the intake of dietary polyphenols may bring numerous benefits due to their antioxidant and anti-inflammatory properties, and their intake has been associated with impaired ageing in humans. Polyphenol intake has been shown to be effective in ameliorating several age-related phenotypes, including oxidative stress, inflammatory processes, impaired proteostasis, and cellular senescence, among other features, which contribute to an increased risk of ageing-associated diseases. This review aims to address, in a general way, the main findings described in the literature about the benefits of polyphenols in each of the hallmarks of ageing, as well as the main regulatory mechanisms responsible for the observed antiageing effects.

Keywords: ageing hallmarks; molecular mechanisms; polyphenols

DOI: https://doi.org/10.3390/ijms24065508