bims-minfam 2022-05-22 papers

Issue of 2022–05–22
nine papers selected by
Ayesh Seneviratne, Western University

Front Genet. 2022 ;13 880421

Dietary Supplements and Natural Products: An Update on Their Clinical Effectiveness and Molecular Mechanisms of Action During Accelerated Biological Aging.

Ye Chen, Sherif Hamidu, Xintong Yang, Yiqi Yan, Qilong Wang, Lin Li, Patrick Kwabena Oduro, Yuhong Li.

Accelerated biological aging, which involves the gradual decline of organ or tissue functions and the distortion of physiological processes, underlies several human diseases. Away from the earlier free radical concept, telomere attrition, cellular senescence, proteostasis loss, mitochondrial dysfunction, stem cell exhaustion, and epigenetic and genomic alterations have emerged as biological hallmarks of aging. Moreover, nutrient-sensing metabolic pathways are critical to an organism's ability to sense and respond to nutrient levels. Pharmaceutical, genetic, and nutritional interventions reverting physiological declines by targeting nutrient-sensing metabolic pathways can promote healthy aging and increase lifespan. On this basis, biological aging hallmarks and nutrient-sensing dependent and independent pathways represent evolving drug targets for many age-linked diseases. Here, we discuss and update the scientific community on contemporary advances in how dietary supplements and natural products beneficially revert accelerated biological aging processes to retrograde human aging and age-dependent human diseases, both from the clinical and preclinical studies point-of-view. Overall, our review suggests that dietary/natural products increase healthspan-rather than lifespan-effectively minimizing the period of frailty at the end of life. However, real-world setting clinical trials and basic studies on dietary supplements and natural products are further required to decisively demonstrate whether dietary/natural products could promote human lifespan.

Keywords: age-related diseases; aging; dietary supplements; mitochondrial dysfunction; natural products; nutrient-sensing pathway

DOI: https://doi.org/10.3389/fgene.2022.880421

Aging Cell. 2022 May 15. e13629

Intermittent methionine restriction reduces IGF-1 levels and produces similar healthspan benefits to continuous methionine restriction.

Jason D Plummer, Jay E Johnson.

A sustained state of methionine restriction (MR) dramatically extends the healthspan of several model organisms. For example, continuously methionine-restricted rodents have less age-related pathology and are up to 45% longer-lived than controls. Promisingly, MR is feasible for humans, and studies have suggested that methionine-restricted individuals may receive similar benefits to rodents. However, long-term adherence to a methionine-restricted diet is likely to be challenging for many individuals. Prompted by this, and the fact that intermittent variants of other healthspan-extending interventions (i.e., intermittent fasting and the cyclic ketogenic diet) are just as effective, if not more, than their continuous counterparts, we hypothesized that an intermittent form of MR might produce similar healthspan benefits to continuous MR. Accordingly, we developed two increasingly stringent forms of intermittent MR (IMR) and assessed whether mice maintained on these diets demonstrate the beneficial metabolic changes typically observed for continuous MR. To the best of our knowledge, we show for the first time that IMR produces similar beneficial metabolic effects to continuous MR, including improved glucose homeostasis and protection against diet-induced obesity and hepatosteatosis. In addition, like continuous MR, IMR confers beneficial changes in the plasma levels of the hormones IGF-1, FGF-21, leptin, and adiponectin. Together, our findings demonstrate that the more practicable intermittent form of MR produces similar healthspan benefits to continuous MR, and thus may represent a more appealing alternative to the classical intervention.

Keywords: IGF-1; aging; intermittent; lifespan; longevity; metabolism; mice; obesity

DOI: https://doi.org/10.1111/acel.13629

Immun Ageing. 2022 May 17. 19(1): 20

NF-κB, a culprit of both inflamm-ageing and declining immunity?

Preeyaporn Songkiatisak, Shah Md Toufiqur Rahman, Mohammad Aqdas, Myong-Hee Sung.

NF-κB is generally recognized as an important regulator of ageing, through its roles in cellular senescence and inflammatory pathways. Activated in virtually all cell-cell communication networks of the immune system, NF-κB is thought to affect age-related defects of both innate and adaptive immune cells, relevant to inflamm-ageing and declining adaptive immunity, respectively. Moreover, the family of NF-κB proteins that exist as heterodimers and homodimers exert their function beyond the immune system. Given their involvement in diverse areas such as DNA damage to metabolism, NF-κB has the potential to serve as linkages between known hallmarks of ageing. However, the complexity of NF-κB dimer composition, dynamic signaling, and tissue-specific actions has received relatively little attention in ageing research. Here, we discuss some areas where further research may bear fruit in our understanding the impact of NF-κB in healthy ageing and longevity.

Keywords: Ageing; Immunosenescence; Inflammation; Mammalian stress pathways; NF-κB

DOI: https://doi.org/10.1186/s12979-022-00277-w

Lancet Infect Dis. 2022 May 13. pii: S1473-3099(22)00314-0. [Epub ahead of print]

Risk of arterial and venous thromboses after COVID-19.

William Whiteley, Angela Wood.

DOI: https://doi.org/10.1016/S1473-3099(22)00314-0

Front Physiol. 2022 ;13 907501

Editorial: Sirtuins From Bench to Bedside: How Far Are We?

Jose Thaiparambil.

Keywords: cvd; genomic instability; inflammation; metabolism; neurodegeneration

DOI: https://doi.org/10.3389/fphys.2022.907501

Front Oncol. 2022 ;12 899502

Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells.

Meixi Peng, Yongxiu Huang, Ling Zhang, Xueya Zhao, Yu Hou.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by multiple cytogenetic and molecular abnormalities, with a very poor prognosis. Current treatments for AML often fail to eliminate leukemic stem cells (LSCs), which perpetuate the disease. LSCs exhibit a unique metabolic profile, especially dependent on oxidative phosphorylation (OXPHOS) for energy production. Whereas, normal hematopoietic stem cells (HSCs) and leukemic blasts rely on glycolysis for adenosine triphosphate (ATP) production. Thus, understanding the regulation of OXPHOS in LSCs may offer effective targets for developing clinical therapies in AML. This review summarizes these studies with a focus on the regulation of the electron transport chain (ETC) and tricarboxylic acid (TCA) cycle in OXPHOS and discusses potential therapies for eliminating LSCs.

Keywords: electron transport chain; leukemic stem cells (LSCs); mitochondria; oxidative phosphorylation (OXPHOS); tricarboxylic acid cycle (TCA cycle)

DOI: https://doi.org/10.3389/fonc.2022.899502

Am J Respir Crit Care Med. 2022 May 17.

Premature Aging of the Airway Epithelium in COPD in People Living with HIV.

Robert J Kaner.

Keywords: COPD; HIV; bronchoscopy; epigenomics; methylation

DOI: https://doi.org/10.1164/rccm.202204-0743ED

Cell Mol Life Sci. 2022 May 18. 79(6): 297

SIRT7 in the aging process.

Francisco Alejandro Lagunas-Rangel.

Aging is the result of the accumulation of a wide variety of molecular and cellular damage over time. This has been associated with a number of features termed hallmarks of aging, including genomic instability, loss of proteostasis, telomere attrition, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and impaired intercellular communication. On the other hand, sirtuins are enzymes with an important role in aging and life extension, of which humans have seven paralogs (SIRT1 to SIRT7). SIRT7 is the least studied sirtuin to date, but it has been reported to serve important functions, such as promoting ribosomal RNA expression, aiding in DNA damage repair, and regulating chromatin compaction. Several studies have established a close relationship between SIRT7 and age-related processes, but knowledge in this area is still scarce. Therefore, the purpose of this review was to analyze how SIRT7 is associated with each of the hallmarks of aging, as well as with some of age-associated diseases, such as cardiovascular diseases, obesity, osteoporosis, and cancer.

Keywords: Aging-associated diseases; Hallmarks of aging; Nucleolus; Ribosomal RNA; Sirtuins

DOI: https://doi.org/10.1007/s00018-022-04342-x