Effects of Physical Exercise on Autophagy and Apoptosis in Aged Brain: Human and Animal Studies

Andreotti, Diana Zukas; Silva, Josiane do Nascimento; Matumoto, Amanda Midori; Orellana, Ana Maria; Mello, Paloma Segura de; Kawamoto, Elisa Mitiko

doi:10.3389/fnut.2020.00094

Cited by 34 publications

(24 citation statements)

References 235 publications

(276 reference statements)

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“…Not only pharmacological treatment may cause upregulation of autophagy. Also physical exercises and diet were found to have a positive effect on both autophagy and the brain function (Andreotti et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cellular Senescence in Brain Aging

Sikora

Bielak-Żmijewska

Dudkowska

et al. 2021

Front. Aging Neurosci.

159

115

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Aging of the brain can manifest itself as a memory and cognitive decline, which has been shown to frequently coincide with changes in the structural plasticity of dendritic spines. Decreased number and maturity of spines in aged animals and humans, together with changes in synaptic transmission, may reflect aberrant neuronal plasticity directly associated with impaired brain functions. In extreme, a neurodegenerative disease, which completely devastates the basic functions of the brain, may develop. While cellular senescence in peripheral tissues has recently been linked to aging and a number of aging-related disorders, its involvement in brain aging is just beginning to be explored. However, accumulated evidence suggests that cell senescence may play a role in the aging of the brain, as it has been documented in other organs. Senescent cells stop dividing and shift their activity to strengthen the secretory function, which leads to the acquisition of the so called senescence-associated secretory phenotype (SASP). Senescent cells have also other characteristics, such as altered morphology and proteostasis, decreased propensity to undergo apoptosis, autophagy impairment, accumulation of lipid droplets, increased activity of senescence-associated-β-galactosidase (SA-β-gal), and epigenetic alterations, including DNA methylation, chromatin remodeling, and histone post-translational modifications that, in consequence, result in altered gene expression. Proliferation-competent glial cells can undergo senescence both in vitro and in vivo, and they likely participate in neuroinflammation, which is characteristic for the aging brain. However, apart from proliferation-competent glial cells, the brain consists of post-mitotic neurons. Interestingly, it has emerged recently, that non-proliferating neuronal cells present in the brain or cultivated in vitro can also have some hallmarks, including SASP, typical for senescent cells that ceased to divide. It has been documented that so called senolytics, which by definition, eliminate senescent cells, can improve cognitive ability in mice models. In this review, we ask questions about the role of senescent brain cells in brain plasticity and cognitive functions impairments and how senolytics can improve them. We will discuss whether neuronal plasticity, defined as morphological and functional changes at the level of neurons and dendritic spines, can be the hallmark of neuronal senescence susceptible to the effects of senolytics.

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Section: Discussionmentioning

confidence: 99%

Cellular Senescence in Brain Aging

Sikora

Bielak-Żmijewska

Dudkowska

et al. 2021

Front. Aging Neurosci.

159

115

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show abstract

“…Exercise is a well-established lifestyle modification that retards aging and increases human healthspan [ 283 ]. Exercise enhances mitophagy and autophagy [ 284 , 285 ], which are associated with the inhibition of mPTP. It was shown that exercise training decreases susceptibility to Ca 2+ -induced mPTP opening in heart mitochondria [ 286 ].…”

Section: Lifespan and Healthspan Extension Paradigms And Mptpmentioning

confidence: 99%

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

Rottenberg¹,

Hoek

2021

Cells

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The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging reactive oxygen species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either inhibit or accelerate aging or retard or enhance the progression of aging-driven degenerative diseases and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles, protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. The increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

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“…ECT rapidly and transiently induces autophagy in the hippocampus [ 119 ], consistent with the rapid and transient antidepressant effect in patients. The antidepressant effects of physical activity [ 120 , 121 ] are compatible with increased autophagy [ 122 , 123 , 124 ]. Mediterranean and other healthy diets have preventive and therapeutic effects on future [ 125 , 126 ] and current [ 127 ] depressive episodes.…”

Section: Sphingolipids In Mddmentioning

confidence: 99%

New Molecular Targets for Antidepressant Drugs

Kornhuber

Gulbins

2021

Pharmaceuticals

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Major depressive disorder (MDD) is a common and severe mental disorder that is usually recurrent and has a high risk of suicide. This disorder manifests not only with psychological symptoms but also multiple changes throughout the body, including increased risks of obesity, diabetes, and cardiovascular disease. Peripheral markers of oxidative stress and inflammation are elevated. MDD is therefore best described as a multisystem whole-body disease. Pharmacological treatment with antidepressants usually requires several weeks before the desired effects manifest. Previous theories of depression, such as the monoamine or neurogenesis hypotheses, do not explain these characteristics well. In recent years, new mechanisms of action have been discovered for long-standing antidepressants that also shed new light on depression, including the sphingolipid system and the receptor for brain-derived neurotrophic factor (BDNF).

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Effects of Physical Exercise on Autophagy and Apoptosis in Aged Brain: Human and Animal Studies

Cited by 34 publications

References 235 publications

Cellular Senescence in Brain Aging

Cellular Senescence in Brain Aging

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

New Molecular Targets for Antidepressant Drugs

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