Stem cells, fitness, and aging

Kitaeva, Kristina; Kiyasov, Andrey; Rizvanov, Albert; Rutland, Catrin; Solovyeva, Valeriya

Abstract

Normal development of organisms is impossible without constant renewal of cells and tissues. Continuous division can lead to the accumulation of unwanted changes in cells, the number of which, increases with age and reduces the functionality of organs. The elimination of defective or abnormal cells, and regeneration of healthy cells, are necessary for proper tissue homeostasis in an adult. It is known that multipotent stem cells (MSCs) are a regenerative pool in the body. They can differentiate into adipocyte, bone, cartilage, muscle, nerve and the other cell types as necessary, therefore, they are point of great interest in the context of regenerative material in medical research. Mesenchymal stem cells are found in adipose tissue, skin, placental tissue, the endometrium, menstrual blood, liver tissue, synovial fluid, dental pulp, muscles, and many other parts of the body. The presence of these cells in a large number of body tissues ensures they function normally. As MSCs age, they lose regenerative potential, which may be associated with age-related diseases in the elderly, therefore these cells are potential therapeutic targets. Senescence of MSCs is characterized by irreversible cycle arrest in the G0/G1 phase, increased expression of proteins associated with aging (in particular, p16, p21, p53) and higher β-galactosidase (SA-β-gal) activity. Senescence of MSCs leads to functionality decrease, phenotypic changes, formation of senescence-associated secretory phenotype (SASP), impaired immunomodulatory function and the ability to undergo aberrant differentiation. One of the main characteristics of cellular aging is considered to be an irreversible halt in proliferation, a turning point in the transition from early to complete aging. In the 1960s, it was discovered that in aging human fibroblast cultures, once they had reached their maximum number of divisions, their cell cycles stopped; this phenomenon was called the “Hayflick Limit.” This aging-related permanent arrest of proliferation, telomere shortening, nontelomeric DNA damage, extreme mitogenic signals, and altered chromatin organization are some of the defining characteristics of aging. However, when a cell reaches the Hayflick Limit or replicative aging, this does not necessarily lead to cell death, loss of functionality, or decreased viability. The senescent cells can still be viable and live in a culture, in contrast to the apoptotic cells that undergo programmed cell death. A number of factors, such as oxidative damage, telomere contraction, hyperproliferation, expression of oncogenes, ultraviolet and γ-ray irradiation, and chemical agents, can trigger DNA damage response in cells. Weak DNA injury usually causes cell cycle arrest, while severe damage can activate a program or program the aging of death, such as apoptosis, necrosis, or autophagy. At the same time, a chronically senescent cell acquires various phenotypic changes, including morphological changes, chromatin remodeling, metabolic reprogramming, and the secretion of factors that form the so-called SASP. In this chapter, we will review the latest data on stem cell aging, focusing in on the aging of MSCs, the reasons why cells lose their functionality during aging, and investigate possible strategies to prevent aging and improve cell fitness.

Citation

Kitaeva, K., Kiyasov, A., Rizvanov, A., Rutland, C., & Solovyeva, V. (2022). Stem cells, fitness, and aging. In P. J. Oliveira, & J. O. Malva (Eds.), Aging: from fundamental biology to societal impact (385-405). Elsevier. https://doi.org/10.1016/B978-0-12-823761-8.00007-0

• Publication Date: 2022
• Deposit Date: Nov 6, 2024
• Publisher: Elsevier
• Pages: 385-405
• Book Title: Aging: from fundamental biology to societal impact
• Chapter Number: 15
• ISBN: 9780128237618
• DOI: https://doi.org/10.1016/B978-0-12-823761-8.00007-0
• Public URL: https://nottingham-repository.worktribe.com/output/25076364
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/B9780128237618000070?via%3Dihub