Vascular Senescence: A Potential Bridge Between Physiological Aging and Neurogenic Decline

Rojas-Vázquez, Sara; Blasco-Chamarro, Laura; López-Fabuel, Irene; Martínez‐Máñez, Ramón; Fariñas, Isabel

doi:10.3389/fnins.2021.666881

Cited by 12 publications

(6 citation statements)

References 147 publications

(249 reference statements)

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“…Putative senescent states have been suggested in a variety of neural subpopulations with ageing and in various disease contexts, including microglia [26][27][28][29][30], neurons [31][32][33], astrocytes [26,34,35], and oligodendrocyte progenitor cells [36]. Vascular and endothelial cells of the blood-brain barrier have also demonstrated senescence properties [37,38]. It is also likely that multiple cell types become senescent in complex diseases, which further complicates the cause-effect relationship between specific populations of senescent cells and disease processes.…”

Section: Introductionmentioning

confidence: 99%

Untangling senescent and damage‐associated microglia in the aging and diseased brain

McNeely

Baker

2021

The FEBS Journal

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Microglial homeostasis has emerged as a critical mediator of health and disease in the central nervous system. In their neuroprotective role as the predominant immune cells of the brain, microglia surveil the microenvironment for debris and pathogens, while also promoting neurogenesis and performing maintenance on synapses. Chronological ageing, disease onset, or traumatic injury promotes irreparable damage or deregulated signaling to reinforce neurotoxic phenotypes in microglia. These insults may include cellular senescence, a stable growth arrest often accompanied by the production of a distinctive pro-inflammatory secretory phenotype, which may contribute to age-or disease-driven decline in neuronal health and cognition and is a potential novel therapeutic target. Despite this increased scrutiny, unanswered questions remain about what distinguishes senescent microglia and non-senescent microglia reacting to insults occurring in ageing, disease, and injury, and how central the development of senescence is in their pivot from guardian to assailant. To intelligently design future studies to untangle senescent microglia from other primed and reactionary states, specific criteria must be developed that define this population and allow for comparisons between different model systems. Comparing microglial activity seen in homeostasis, ageing, disease, and injury allows for a more coherent understanding of when and how senescent and other harmful microglial subpopulations should be targeted.

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Section: Introductionmentioning

confidence: 99%

Untangling senescent and damage‐associated microglia in the aging and diseased brain

McNeely

Baker

2021

The FEBS Journal

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“…Cellular senescence may contribute to aging-related BBB leakage and has gained a lot of attention in recent years [ 154 , 155 , 156 , 157 ]. Cellular senescence within the NVU or BBB is observed in the brains of patients with Alzheimer’s and Parkinson’s diseases [ 71 , 158 , 159 , 160 ].…”

Section: Considerations For Brain Agingmentioning

confidence: 99%

Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence

Vielee

Wise

2023

Brain Sciences

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Advancements in modern medicine have improved the quality of life across the globe and increased the average lifespan of our population by multiple decades. Current estimates predict by 2030, 12% of the global population will reach a geriatric age and live another 3–4 decades. This swelling geriatric population will place critical stress on healthcare infrastructures due to accompanying increases in age-related diseases and comorbidities. While much research focused on long-lived individuals seeks to answer questions regarding how to age healthier, there is a deficit in research investigating what aspects of our lives accelerate or exacerbate aging. In particular, heavy metals are recognized as a significant threat to human health with links to a plethora of age-related diseases, and have widespread human exposures from occupational, medical, or environmental settings. We believe heavy metals ought to be classified as a class of gerontogens (i.e., chemicals that accelerate biological aging in cells and tissues). Gerontogens may be best studied through their effects on the “Hallmarks of Aging”, nine physiological hallmarks demonstrated to occur in aged cells, tissues, and bodies. Evidence suggests that cellular senescence—a permanent growth arrest in cells—is one of the most pertinent hallmarks of aging and is a useful indicator of aging in tissues. Here, we discuss the roles of heavy metals in brain aging. We briefly discuss brain aging in general, then expand upon observations for heavy metals contributing to age-related neurodegenerative disorders. We particularly emphasize the roles and observations of cellular senescence in neurodegenerative diseases. Finally, we discuss the observations for heavy metals inducing cellular senescence. The glaring lack of knowledge about gerontogens and gerontogenic mechanisms necessitates greater research in the field, especially in the context of the global aging crisis.

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“…Liu-Ambrose and colleagues [ 116 , 117 , 118 , 119 ] have discussed the ability of exercise in perhaps pre-menopausal females and beyond to prevent or inhibit the vascular-related changes that may lead to dementia or loss of cognition, implying that the cognitive changes in the brain cells may be indirect and associated with loss of vascular integrity in a subset of post-menopausal females. Sex differences in loss of cognition may therefore result from sex differences in regulation of the vascular component of specific tissues in the brain [ 120 , 121 ] during the aging process and vascular senescence [ 122 , 123 ]. As endothelial cells are heterogenous and appear to form a specific paracrine relationship with cells in different tissues [ 124 , 125 , 126 ], variation in the vascular contribution to different forms of dementia or cognition loss may occur.…”

Section: The Way Forwardmentioning

confidence: 99%

Use of Brain-Derived Stem/Progenitor Cells and Derived Extracellular Vesicles to Repair Damaged Neural Tissues: Lessons Learned from Connective Tissue Repair Regarding Variables Limiting Progress and Approaches to Overcome Limitations

Hart

2023

IJMS

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Pluripotent neural stem or progenitor cells (NSC/NPC) have been reported in the brains of adult preclinical models for decades, as have mesenchymal stem/stromal cells (MSC) been reported in a variety of tissues from adults. Based on their in vitro capabilities, these cell types have been used extensively in attempts to repair/regenerate brain and connective tissues, respectively. In addition, MSC have also been used in attempts to repair compromised brain centres. However, success in treating chronic neural degenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and others with NSC/NPC has been limited, as have the use of MSC in the treatment of chronic osteoarthritis, a condition affecting millions of individuals. However, connective tissues are likely less complex than neural tissues regarding cell organization and regulatory integration, but some insights have been gleaned from the studies regarding connective tissue healing with MSC that may inform studies attempting to initiate repair and regeneration of neural tissues compromised acutely or chronically by trauma or disease. This review will discuss the similarities and differences in the applications of NSC/NPC and MSC, where some lessons have been learned, and potential approaches that could be used going forward to enhance progress in the application of cellular therapy to facilitate repair and regeneration of complex structures in the brain. In particular, variables that may need to be controlled to enhance success are discussed, as are different approaches such as the use of extracellular vesicles from stem/progenitor cells that could be used to stimulate endogenous cells to repair the tissues rather than consider cell replacement as the primary option. Caveats to all these efforts relate to whether cellular repair initiatives will have long-term success if the initiators for neural diseases are not controlled, and whether such cellular initiatives will have long-term success in a subset of patients if the neural diseases are heterogeneous and have multiple etiologies.

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Vascular Senescence: A Potential Bridge Between Physiological Aging and Neurogenic Decline

Cited by 12 publications

References 147 publications

Untangling senescent and damage‐associated microglia in the aging and diseased brain

Untangling senescent and damage‐associated microglia in the aging and diseased brain

Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence

Use of Brain-Derived Stem/Progenitor Cells and Derived Extracellular Vesicles to Repair Damaged Neural Tissues: Lessons Learned from Connective Tissue Repair Regarding Variables Limiting Progress and Approaches to Overcome Limitations

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