Sirtuins-Mediated System-Level Regulation of Mammalian Tissues at the Interface between Metabolism and Cell Cycle: A Systematic Review

Maissan, Parcival; Mooij, Eva J; Barberis, Matteo

doi:10.3390/biology10030194

Cited by 20 publications

(31 citation statements)

References 707 publications

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“…As stated, HU during senescence induction promotes an elevation of cellular ROS in part because of downregulation of SOD2, and recently, it was reported that this drug could also inhibit the expression of Sirt-3 ( Figure 4 ) [ 156 ]. Sirt-3 is a mitochondrial deacetylase that regulates major mitochondrial biological processes, including ATP generation, ROS detoxification, nutrient oxidation, mitochondrial dynamics, and the unfolded protein response [ 181 , 182 ]. Sirt-3 also deacetylates and thereby activates SOD-2 [ 183 ].…”

Section: Hydroxyurea and Cellular Senescencementioning

confidence: 99%

Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?

Kapor

Čokić

Santibáñez

2021

Oxidative Medicine and Cellular Longevity

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Hydroxyurea (HU) is a water-soluble antiproliferative agent used for decades in neoplastic and nonneoplastic conditions. HU is considered an essential medicine because of its cytoreduction functions. HU is an antimetabolite that inhibits ribonucleotide reductase, which causes a depletion of the deoxyribonucleotide pool and dramatically reduces cell proliferation. The proliferation arrest, depending on drug concentration and exposure, may promote a cellular senescence phenotype associated with cancer cell therapy resistance and inflammation, influencing neighboring cell functions, immunosuppression, and potential cancer relapse. HU can induce cellular senescence in both healthy and transformed cells in vitro, in part, because of increased reactive oxygen species (ROS). Here, we analyze the main molecular mechanisms involved in cytotoxic/genotoxic HU function, the potential to increase intracellular ROS levels, and the principal features of cellular senescence induction. Understanding the mechanisms involved in HU’s ability to induce cellular senescence may help to improve current chemotherapy strategies and control undesirable treatment effects in cancer patients and other diseases.

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Section: Hydroxyurea and Cellular Senescencementioning

confidence: 99%

Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?

Kapor

Čokić

Santibáñez

2021

Oxidative Medicine and Cellular Longevity

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“…Thus, sirtuins in breast milk are strong candidates for mediating the positive impact of breast feeding on the health of neonates and children. A recent review suggested a role of sirtuins in pre-and postnatal programming, which may result in (metabolic) diseases during later life [25]. Additionally, sirtuins 1, 2, and 3 have been shown to modulate neurodegeneration in the enteric nervous system [26] and may impact the brain by the microbiota-gut-brain axis, which has been suggested to be involved in priming important organ systems via early-life nutrition [27].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Sirtuin 1 and Sirtuin 3 at Enzyme and Protein Levels in Human Breast Milk during the Neonatal Period

et al. 2021

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Breast feeding is regarded as the preferred nutrition modality for children during the first few months of life. It not only furthers growth and development but also is supposed to impact later life. The first 1000 days are regarded as a critical window for development, even beyond infancy. The physiological basis underlying this beneficial effect is not clear. Sirtuins are important regulatory proteins of metabolism and are supposed to play a critical role in ageing and longevity as well as in diseases. In the present study, we developed novel methods to assay sirtuin 1 and sirtuin 3 at enzyme activity (via fluorometry) and protein levels (by Western blot) in the aqueous phase and in the cell pellet of human breast milk and assessed the impact of ongoing lactation during the neonatal period. Sirtuin activities in the aqueous phase were negatively correlated with the duration of lactation in the neonatal period. There was no correlation of sirtuin activities in the cell pellet with the duration of lactation. The amounts of sirtuin 1 and sirtuin 3 measured by Western blot were negatively correlated with the lactation period.

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“…SIRT6 deacetylates H3K56ac, H3K18ac and H3K9ac, and SIRT7 deacetylation activity is directed towards H3K18ac and H3K36ac. Sirtuins are ubiquitously expressed proteins with important roles in numerous tissues [19]. At the organismal level, nuclear sirtuins play major roles in determining the onset of aging and the health-span.…”

Section: Introductionmentioning

confidence: 99%

“…Sirtuins are ubiquitously expressed proteins with important roles in numerous tissues [ 19 ]. At the organismal level, nuclear sirtuins play major roles in determining the onset of aging and the health-span.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Sirtuins and the Aging of the Immune System

Gamez-Garcia

Vázquez

2021

Genes

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The immune system undergoes major changes with age that result in altered immune populations, persistent inflammation, and a reduced ability to mount effective immune responses against pathogens and cancer cells. Aging-associated changes in the immune system are connected to other age-related diseases, suggesting that immune system rejuvenation may provide a feasible route to improving overall health in the elderly. The Sir2 family of proteins, also called sirtuins, have been broadly implicated in genome homeostasis, cellular metabolism, and aging. Sirtuins are key responders to cellular and environmental stress and, in the case of the nuclear sirtuins, they do so by directing responses to chromatin that include gene expression regulation, retrotransposon repression, enhanced DNA damage repair, and faithful chromosome segregation. In the immune system, sirtuins instruct cellular differentiation from hematopoietic precursors and promote leukocyte polarization and activation. In hematopoietic stem cells, sirtuins safeguard quiescence and stemness to prevent cellular exhaustion. Regulation of cytokine production, which, in many cases, requires NF-κB regulation, is the best-characterized mechanism by which sirtuins control innate immune reactivity. In adaptive immunity, sirtuins promote T cell subset differentiation by controlling master regulators, thereby ensuring an optimal balance of helper (Th) T cell-dependent responses. Sirtuins are very important for immune regulation, but the means by which they regulate immunosenescence are not well understood. This review provides an integrative overview of the changes associated with immune system aging and its potential relationship with the roles of nuclear sirtuins in immune cells and overall organismal aging. Given the anti-aging properties of sirtuins, understanding how they contribute to immune responses is of vital importance and may help us develop novel strategies to improve immune performance in the aging organism.

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Sirtuins-Mediated System-Level Regulation of Mammalian Tissues at the Interface between Metabolism and Cell Cycle: A Systematic Review

Cited by 20 publications

References 707 publications

Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?

Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?

Analysis of Sirtuin 1 and Sirtuin 3 at Enzyme and Protein Levels in Human Breast Milk during the Neonatal Period

Nuclear Sirtuins and the Aging of the Immune System

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