A broad range of degenerative disorders present with an underlying mitochondrial dysfunction. Various environmental triggers such as air pollutants, smoking, and poor lifestyle induce oxidative stress, which may compromise mitochondrial integrity. An adoption of yoga-based lifestyle may hold the key to increase mitochondrial copy number, optimize oxidative stress markers, and increase the expression levels of transcripts that maintain mitochondrial integrity, and reduce associated consequences on physical and mental health,and hence can be beneficial as an adjunct therapy. Keywords Free radicals, inflammation, mitochondrial integrity, oxidative stress, yoga Received 04 December 2020; accepted 11 December 2020 weakness with ataxia and retinitis pigmentosa, or Leigh syn- Manuscript drome, and Leber hereditary optic neuropathy (LHON). Yoga Mitochondria are cytoplasmic organelles responsible for life is an ancient mind and body practice that enhances wellness, and are the power house of the cell. They play an important promotes health, prevents the onset of diseases, and can be regulatory role in energy metabolism, apoptosis, reduction– used as an adjunct therapy in complex diseases. Yoga improves oxidation potential, free radicals scavenging, and intracellular the mitochondrial and nuclear deoxyribonucleic acid (DNA) 3,4 calcium regulation. Mitochondrial dysfunction can result in a integrity and positively impacts the sperm epigenome. Yoga broad range of degenerative disorders such as encephalopa- is a profound science that works through a well-defined psy- thies, cardiomyopathy, aging, cancer, diabetes, Alzheimer’s cho-neuro-immune axis, which affects a variety of processes disease, Parkinson’s disease, and Huntington’s disease. from basic metabolism, epigenetics, DNA repair, oxidative Unhealthy social habits, genetic mutations, epigenetic factors, bioprocesses to aging, blood pressure, organ system mainte- 3,5–8 stress, exposure to infections, allergens, and toxins may con- nance, subjective well-being, and reproductive health. A tribute to selective disease susceptibility associated with pilot study from our lab showed that there was a reduction in increased mitochondrial fragmentation and dysfunctional blurring and clouding of vision after eight weeks of mitochondria. Such mitochondria produce supraphysiological levels of free radicals and low levels of adenosine triphos- phate. Mitochondrial diseases are highly recessive in nature and exhibit a threshold effect. When the number of mutant mitochondria crosses a certain threshold, it adversely impacts Laboratory for Molecular Reproduction and Genetics, Department of the tissue function. Thus, tissues with high energy demand Anatomy, All India Institute of Medical Sciences, New Delhi, India first manifest the disease as they have a lower threshold and Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute thus low levels of mutant mitochondria can disrupt the func- of Medical Sciences, New Delhi, India tion of such tissues. A group of diseases are caused by the Corresponding author: damage to mitochondria such as the Kearns–Sayre syndrome, Rima Dada,Laboratory for Molecular Reproduction and Genetics,Room chronic progressive external ophthalmoplegia, mitochondrial No: 1036, Department of Anatomy,All India Institute of Medical Sciences, encephalomyopathy with lactic acidosis and stroke-like epi- New Delhi 110029, India. sodes, myoclonic epilepsy with ragged-red fibers, neurogenic E-mail: email@example.com Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-Commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https:// us.sagepub.com/en-us/nam/open-access-at-sage). 2 Annals of Neurosciences yoga-based lifestyle intervention (YBLI) in LHON patients. associated with many positive and objectively measurable There was no further deterioration in vision, and they were changes in an individual, which include reducing stress and able to complete visual tasks such as recognizing faces and anxiety, warding off depression, improving sleep, reducing objects after the regular daily practice of yoga. This could be sympathetic distress, reducing hypertension symptoms, explained by the improvement in mitochondrial integrity post- decreasing inflammation, and improving the quality of 8,13,14,16–18 yoga practice as there was an increase in the mitochondrial life. The relaxation response elicited due to yoga membrane potential, levels of nicotinamide adenine dinucleo- leads to an elevation of β-endorphins, improvement in cardio- tide (NAD+), cytochrome c oxidase (COX-II), mitochondrial vagal tone, reducing sympathetic overactivity, lowering of 12,19,20 copy number, and expression of genes that maintain mito- IOP, and reduces further damage to RGCs. Yoga is also chondrial integrity and promote mitochondrial biogenesis known to enhance cognitive abilities, boosting memory, (AMPK, IGF1R, PRC-1, TFAM, SIRT-1, TIMP-1, and increasing thickness of cerebral cortex, neural connectivity, KLOTHO). It also increases the levels of melatonin, a master positive changes in electroencephalogram (EEG), and regulatory molecule that regulates the sleep–wake cycle and is improving neuroplasticity. Yoga aids in the maintenance of a potent antioxidant whose highest subcellular concentration genomic stability and chromosomal integrity, reducing the is in mitochondria and since mitochondria are both the source rate of cellular aging by maintaining telomere length and and target of free radical-induced damage, an increase in mel- upregulation of telomerase activity and the increase in 13,14 atonin levels plays a key role in minimizing the oxidative expression levels of sirtuins. Yoga normalizes the levels of damage to mitochondrial (mt) DNA and thereby reducing mt transcripts involved in DNA repair, cell cycle checkpoint mutations. LHON is a rare mitochondrial retinopathy caused control, and causes the downregulation of pro-inflammatory by the respiratory chain dysfunction that leads to oxidative genes. A study from our laboratory documented positive stress (OS) and insufficient energy supply, which results in effects of YBLI in RA, which is a severe autoimmune enhanced apoptosis of retinal ganglion cells (RGCs). This is inflammatory disorder characterized by chronic pain and 21,22,23 an underlying pathology of LHON, and in primary open-angle swelling, primarily affecting the peripheral joints. Our glaucoma (POAG) too, there is enhanced apoptosis of RGCs. recent randomized controlled trial (RCT) on the impact of Although it was believed that intraocular pressure (IOP) is the yoga on RA patients published in Frontiers in Psychology, only modifiable risk factor in glaucoma, recent studies have 2020 supports yoga as an adjunctive therapy to treat this shown that an increase in IOP, ischemia, hypoxia, OS, gluta- chronic progressive debilitating disease as it aids in decreasing mate excitotoxicity, low levels of brain-derived neurotrophic systemic inflammation by its beneficial effects on the psycho- factor (BDNF), inflammation of glial cells, and increased lev- neuro-immune axis and normalization of dysregulated els of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transcripts (IL-6, TNF-α, NFKB1, TGF-β, and CTLA4). Yoga and nuclear factor kappa B (NFKB) are the factors which improves the mitochondrial integrity by altering the expression 9–11 cause enhanced apoptosis of RGCs in POAG. In LHON, levels of transcripts that maintain mitochondrial integrity, treatment strategies included giving anti-inflammatory, anti- which aids in the maintenance of optimal free radical levels, oxidants, neuroprotectants, and antiapoptotic agents. Recent holds the key to increase the mitochondrial copy number, studies from our lab showed that yoga and meditation cause a improves COX-II activity, increases NAD+ levels, optimizes decline in expression levels of pro-inflammatory genes such OS markers, and increases the expression levels of transcripts as TNF-α, NFKB, and IL-6, and upregulation of anti-inflam- that maintain mitochondrial integrity, reduces disease activity matory, antiapoptotic, antioxidant genes and genes maintain- and its associated consequences on physical and mental 4,22,23 ing neuroplasticity [BDNF, dehydroepiandrosterone (DHEA), health,and hence can be beneficial as an adjunct therapy. nerve growth factor receptor (NGFR), and neuregulin] and The regulation of cellular OS within physiological limits 8,9,12–14 regulating the blood flow in POAG. This has also been after YBLI suggests the potential of this intervention in documented in other complex diseases such as unexplained protecting cells from OS-induced nuclear and mt DNA male factor infertility and rheumatoid arthritis (RA). Thus, damage and telomere attrition and in reversing epigenetic yoga by improvement in mt integrity and mt copy number changes, which accumulate due to unhealthy lifestyle and may be beneficial in diseases where there is a reduced energy adverse environmental conditions. The multifaceted production secondary to mitochondrial dysfunction, and hence dimensions of yoga enhance psychological and physical yoga warrants larger studies in different mitochondrial dis- health by its underlying cumulative effects on maintaining eases and some of such studies are ongoing in our laboratory. the mitochondrial and nuclear genome.Yoga is a cost-effective Yoga optimizes self-regulatory mechanisms by stress emerging health discipline which unlike drugs has no side- modulation on physical, emotional, and psychological levels effects and aids in reducing disease severity, optimizes OS via high-level and low-level brain networks. Yoga enhances levels, increases transcript levels associated with immune focused attention during different asanas (physical postures), homeostasis, immune system metabolism, mitochondrial pranayama (breathing techniques), dhyana (meditation), and architecture, and mitochondrial biogenesis, and hence has the savasana (relaxation techniques), and is termed as “meditation immense potential to be used as an adjunct therapy in the in motion.” It works through many mechanisms and has been management of mitochondrial diseases. Gautam et al. 3 Declaration of Conflicting Interests 11. Dada T, Bhai N, Midha N, et al. Effect of mindfulness medi- tation on intraocular pressure and trabecular meshwork gene The authors declared no potential conflicts of interest with respect to expression: A randomized controlled trial. Am J Ophthalmol the research, authorship, and/or publication of this article. 2021; 223: 308–321. 12. Gagrani M, Faiq MA, Sidhu T, et al. 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Annals of Neurosciences – SAGE
Published: Jan 1, 2021