Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease

Abstract

The mechanisms that underlie the pathophysiology of aging, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and stroke are not fully understood and have been the focus of intense and constant investigation worldwide. Studies that provide insights on aging and age-related disease mechanisms are critical for advancing novel therapies that promote successful aging and prevent or cure multiple age-related diseases. The April 2019 issue of the journal, "Aging & Disease" published a series of articles that confer fresh insights on numerous age-related conditions and diseases. The age-related topics include the detrimental effect of overweight on energy metabolism and muscle integrity, senoinflammation as the cause of neuroinflammation, the link between systemic C-reactive protein and brain white matter loss, the role of miR-34a in promoting healthy heart and brain, the potential of sirtuin 3 for reducing cardiac and pulmonary fibrosis, and the promise of statin therapy for ameliorating asymptomatic intracranial atherosclerotic stenosis. Additional aging-related articles highlighted the involvement of miR-181b-5p and high mobility group box-1 in hypertension, Yesassociated protein in cataract formation, multiple miRs and long noncoding RNAs in coronary artery disease development, the role of higher meat consumption on sleep problems, and the link between glycated hemoglobin and depression. The topics related to ALS suggested that individuals with higher education and living in a rural environment have a higher risk for developing ALS, and collagen XIX alpha 1 is a prognostic biomarker of ALS. The topics discussed on AD implied that extracellular amyloid β42 is likely the cause of intraneuronal neurofibrillary tangle accumulation in familial AD and traditional oriental concoctions may be useful for slowing down the progression of AD. The article on stroke suggested that inhibition of the complement system is likely helpful in promoting brain repair after ischemic stroke. The significance of the above findings for understanding the pathogenesis in aging, ALS, AD, and stroke, slowing down the progression of aging, ALS and AD, and promoting brain repair after stroke are discussed.

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“…With the population of older adults is increasing greatly worldwide, "Aging & Disease" has become a hot topic in our society (Shetty et al, 2019), and aging is the predominant risk factor for various age-related diseases (Franceschi et al, 2018), including cancer, cardiovascular disorder, diabetes mellitus, Parkinson's disease, Huntington's disease, and Alzheimer's disease (AD). AD is a severe neurodegenerative disease and the m o s t p r e v a l e n t f o r m o f d e m e n t i a , w i t h s p e c i fi c neuropathological features, including amyloid protein deposits, neurofibrillary tangles, synaptic dysfunction (Marsh and Alifragis, 2018), and neuronal loss (Ossenkoppele et al, 2015).…”

Adipose-derived stromal stem cells (ASCs) as a new regenerative immediate therapy combating coronavirus (COVID-19)-induced pneumonia

“…Intravenous infusion of MSCs leads in fact to their accumulation in the narrow capillaries of the lungs [41], where their activities playing a significant role in protecting or rejuvenating alveolar epithelial cells, counteracting fibrosis, and improving lung function. MSC infusion would likely be particularly beneficial to elderly individuals infected with SARS-CoV-2, both with and without co-morbidities, as this population is more susceptible to SARS-CoV-2-induced pneumonia, resulting in severe respiratory distress and death because of immune-senescence [42][43][44][45].…”

The Interstitial System of the Brain in Health and Disease

“…Significant transformations ensue in ISS during the development of the brain due to events such as neurogenesis, neuronal migration and differentiation, expansion of dendritic tree, synaptogenesis, gliogenesis, synaptic stripping by microglia, and myelination [1,[5][6][7][8][9][10]. The geometry of the brain ISS also undergoes modification in aging due to the loss of synapses, neurons, dendritic regression, changes in morphology and numbers of glia, senoinflammation, and deposition of amyloid plaques [11][12][13][14][15]. In conditions such as epilepsy, the synchronized firing of a population of neurons may considerably change the geometry of ISS as well as the ISF drainage [16].…”