Cellular and Mitochondrial Quality Control Mechanisms in Maintaining Homeostasis in Aging

Langeh, Urvashi; Kumar, Vishal; Kumar, Anoop; Kumar, Pradeep; Singh, Charan; Singh, Arti

doi:10.1089/rej.2022.0027

Cited by 6 publications

(3 citation statements)

References 77 publications

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“…In addition, since EVs derived from stem cells may be envisioned as attractive medicinal therapeutic products for future cell-free paracrine treatment, also in consideration of their presumed low immunogenicity [ 46 ], the glyoxalase system could also play a role in this fascinating applicative ambit. Interestingly, since also autophagosomes can be a source of EVs, through the “secretory autophagy” pathway [ 47 ], and autophagy, as well as glyoxalases, participate to maintain cellular homeostasis and longevity [ 48 , 49 ], it is also fascinating to hypothesize that glyoxalase-containing EVs might be somehow involved in aging control.…”

Section: Discussionmentioning

confidence: 99%

The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles

2022

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The glyoxalase system is a ubiquitous cellular metabolic pathway whose main physiological role is the removal of methylglyoxal (MG). MG, a glycolysis byproduct formed by the spontaneous degradation of triosephosphates glyceraldehyde-3-phosphate (GA3P) and dihydroxyacetonephosphate (DHAP), is an arginine-directed glycating agent and precursor of the major advanced glycation end product arginine-derived, hydroimidazolone (MG-H1). Extracellular vesicles (EVs) are a heterogeneous family of lipid-bilayer-vesicular structures released by virtually all living cells, involved in cell-to-cell communication, specifically by transporting biomolecules to recipient cells, driving distinct biological responses. Emerging evidence suggests that included in the EVs cargo there are different metabolic enzymes. Specifically, recent research has pointed out that EVs derived from human amniotic fluid stem cell (HASC-EVs) contain glycolytic pay-off phase enzymes, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Since GAPDH catalyzes the sixth step of glycolysis using as a substrate GA3P, from which MG spontaneously origins, we wanted to investigate whether MG-derived MG-H1, as well as glyoxalases, could be novel molecule cargo in these EVs. By using immunoassays and spectrophotometric methods, we found, for the first time ever, that HASC-EVs contain functional glyoxalases and MG-H1, pioneering research to novel and exciting roles of these eclectic proteins, bringing them to the limelight once more.

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Section: Discussionmentioning

confidence: 99%

The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles

2022

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“…The functional state of the mitochondria also determines the overall aging rate and quality of the oocyte which impacts fertility, mitochondrial fusion, which is regulated by two major mitofusins (MFN1/2) and dynamin-like 120 kDa protein (OPA1), and prevails aiding in the maintenance of healthy mitochondria. On the contrary, when mitochondria undergo fission, they exhibit membrane depolarization, depressed ATP production and are usually destroyed by mitophagy [ 132 ]. Like other molecular processes, mitophagy also diminishes with age, thereby preserving more dysfunctional mitochondria and contributing to fewer healthy oocytes [ 133 ]; less than optimally functioning oocytes are incompatible with successful reproduction.…”

Section: Physiological/biological Ovarian Aging: Protection Using Mel...mentioning

confidence: 99%

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

et al. 2023

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Aging has a major detrimental effect on the optimal function of the ovary with changes in this organ preceding the age-related deterioration in other tissues, with the middle-aged shutdown leading to infertility. Reduced fertility and consequent inability to conceive by women in present-day societies who choose to have children later in life leads to increased frustration. Melatonin is known to have anti-aging properties related to its antioxidant and anti-inflammatory actions. Its higher follicular fluid levels relative to blood concentrations and its likely synthesis in the oocyte, granulosa, and luteal cells suggest that it is optimally positioned to interfere with age-associated deterioration of the ovary. Additionally, the end of the female reproductive span coincides with a significant reduction in endogenous melatonin levels. Thus, the aims are to review the literature indicating melatonin production in mitochondria of oocytes, granulosa cells, and luteal cells, identify the multiple processes underlying changes in the ovary, especially late in the cessation of the reproductive life span, summarize the physiological and molecular actions of melatonin in the maintenance of normal ovaries and in the aging ovaries, and integrate the acquired information into an explanation for considering melatonin in the treatment of age-related infertility. Use of supplemental melatonin may help preserve fertility later in life and alleviate frustration in women delaying childbearing age, reduce the necessity of in vitro fertilization–embryo transfer (IVF-ET) procedures, and help solve the progressively increasing problem of non-aging-related infertility in women throughout their reproductive life span. While additional research is needed to fully understand the effects of melatonin supplementation on potentially enhancing fertility, studies published to date suggest it may be a promising option for those struggling with infertility.

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“…Moreover, the quality control of mitochondria and other damaged macromolecules is one of the essential mechanisms for maintaining the cellular homeostasis [ 46 ]; therefore, this applies to muscle cells. In fact, the selective autophagy occurs to specifically remove damaged and dysfunctional organelles whose excessive rates are hallmark of sarcopenia and correlated musculoskeletal diseases, including bone metabolic disorders [ 47 , 48 ].…”

Section: Introductionmentioning

confidence: 99%

Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge

Galasso

Cappella

Mulè

et al. 2023

IJMS

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Autophagy dysregulation is commonplace in the pathogenesis of several invalidating diseases, such as musculoskeletal diseases. Polyamines, as spermidine and spermine, are small aliphatic cations essential for cell growth and differentiation, with multiple antioxidant, anti-inflammatory, and anti-apoptotic effects. Remarkably, they are emerging as natural autophagy regulators with strong anti-aging effects. Polyamine levels were significantly altered in the skeletal muscles of aged animals. Therefore, supplementation of spermine and spermidine may be important to prevent or treat muscle atrophy. Recent in vitro and in vivo experimental studies indicate that spermidine reverses dysfunctional autophagy and stimulates mitophagy in muscles and heart, preventing senescence. Physical exercise, as polyamines, regulates skeletal muscle mass inducing proper autophagy and mitophagy. This narrative review focuses on the latest evidence regarding the efficacy of polyamines and exercise as autophagy inducers, alone or coupled, in alleviating sarcopenia and aging-dependent musculoskeletal diseases. A comprehensive description of overall autophagic steps in muscle, polyamine metabolic pathways, and effects of the role of autophagy inducers played by both polyamines and exercise has been presented. Although literature shows few data in regard to this controversial topic, interesting effects on muscle atrophy in murine models have emerged when the two “autophagy-inducers” were combined. We hope these findings, with caution, can encourage researchers to continue investigating in this direction. In particular, if these novel insights could be confirmed in further in vivo and clinical studies, and the two synergic treatments could be optimized in terms of dose and duration, then polyamine supplementation and physical exercise might have a clinical potential in sarcopenia, and more importantly, implications for a healthy lifestyle in the elderly population.

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Cellular and Mitochondrial Quality Control Mechanisms in Maintaining Homeostasis in Aging

Cited by 6 publications

References 77 publications

The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles

The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge

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