bims-aucach 2022-04-24 papers

bims-aucach

Biomed News

on Autophagy and cachexia

Issue of 2022–04–24
thirteen papers selected by
Kleiton Silva, Rowan University

Mitochondrial fusion- and fission-related protein expression in the regulation of skeletal muscle mass.
Association between Active Mobility Index and sarcopenia among Japanese community-dwelling older adults.
Autophagy in muscle regeneration: potential therapies for myopathies.
Interventions to Improve Body Composition, Upper and Lower Extremity Muscle Strength, and Balance Ability of Older Female Adults: An Intervention Study.
Association between sarcopenia and clinical outcomes in chronic kidney disease patients: A systematic review and meta-analysis.
Effect of semi-recumbent vibration exercise on muscle outcomes in older adults: a pilot randomized controlled clinical trial.
Effects of the FNDC5/Irisin on Elderly Dementia and Cognitive Impairment.
Longitudinal Association between Sarcopenia and Cognitive Impairment among Older Adults in Rural Malaysia.
Frailty and sarcopenia among Turkish people aged 40 and above living with HIV.
Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.
Identification of Coenzyme Q10 and Skeletal Muscle Protein Biomarkers as Potential Factors to Assist in the Diagnosis of Sarcopenia.
P62/SQSTM1 beyond Autophagy: Physiological Role and Therapeutic Applications in Laboratory and Domestic Animals.
Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer's Disease.

Physiol Rep. 2022 Apr;10(8): e15281

Mitochondrial fusion- and fission-related protein expression in the regulation of skeletal muscle mass.

Daiki Nakano, Shuichi Machida.

  Mitochondria in the skeletal muscle are essential for maintaining metabolic plasticity and function. Mitochondrial quality control encompasses the dynamics of the biogenesis and remodeling of mitochondria, characterized by the constant fission and fusion of mitochondria in response to metabolic stressors. However, the roles of mitochondrial fission or fusion in muscle hypertrophy and atrophy remain unclear. The aim of this study was to determine whether mitochondrial fusion and fission events are influenced by muscle hypertrophy or atrophy stimulation. Twenty-six male F344 rats were randomly assigned to a control group or were subjected to up to 14 days of either plantaris overload (via tenotomy of the gastrocnemius and soleus muscles; hypertrophy group) or hindlimb cast immobilization (atrophy group). After 14 days of treatment, plantaris muscle samples were collected to determine the expression levels of mitochondrial fusion- and fission-related proteins. Muscle weight and total muscle protein content increased following plantaris overload in the hypertrophy group, but decreased following immobilization for 14 days in the atrophy group. In the hypertrophied muscle, the level of activated dynamin-related protein 1 (Drp1), phosphorylated at Ser616, significantly increased by 25.8% (p = 0.014). Moreover, the protein expression level of mitochondrial fission factor significantly decreased by 36.5% in the hypertrophy group compared with that of the control group (p = 0.017). In contrast, total Drp1 level significantly decreased in the atrophied plantaris muscle (p = 0.011). Our data suggest that mitochondrial fission events may be influenced by both muscle hypertrophy and atrophy stimulation, and that mitochondrial fission- related protein Drp1 plays an important role in the regulation of skeletal muscle in response to mechanical stimulation.

Keywords:  Drp1; atrophy; hypertrophy; mitochondrial quality control

DOI:  https://doi.org/10.14814/phy2.15281
J Cachexia Sarcopenia Muscle. 2022 Apr 19.

Association between Active Mobility Index and sarcopenia among Japanese community-dwelling older adults.

Satoshi Kurita, Takehiko Doi, Kota Tsutsumimoto, Sho Nakakubo, Yuto Kiuchi, Kazuhei Nishimoto, Hiroyuki Shimada.

   BACKGROUND: A physically active lifestyle, including physical and social activities, is needed to maintain muscle mass, strength, and physical performance. A large life space characterizes an active lifestyle, but the association between life space with physical and social activities and sarcopenia is unclear. This study aimed to examine the association between life space with physical and social activities, assessed using the Active Mobility Index (AMI), and sarcopenia in community-dwelling Japanese older adults.
METHODS: This study used a large, cross-sectional cohort dataset from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes (NCGG-SGS). Between 2013 and 2018, community-dwelling Japanese adults aged ≥60 years participated in the NCGG-SGS. Sarcopenia was identified by measuring muscle mass and strength based on the clinical definition. The secondary outcomes were sarcopenia indices, including lower muscle mass, lower muscle strength, and lower gait speed. AMI assessed life space with physical and social activities in each life space (distance from the respondent's home: <1, 1-10, or >10 km) during the past month by noting the frequency, primary purpose, type of transportation, interaction with others, and physical activity. The associations between quartile groups of AMI total, physical, and social scores and sarcopenia were examined using a logistic regression model.
RESULTS: From all participants, 21 644 participants (age 73.5 ± 5.8 years, 54.7% female) were included in the analysis. The prevalence of sarcopenia was 4.1% (n = 894). For the AMI total score, referred to Q1 group, Q3 and Q4 groups were significantly associated with a reduced odds ratio (OR) of sarcopenia after adjusting for all covariates [adjusted OR (aOR) (95% confidence interval), Q3: 0.71 (0.57-0.89), Q4: 0.69 (0.55-0.87)]. Q3 and Q4 of the AMI physical score groups were also significantly associated with reduced OR of sarcopenia [Q3: 0.71 (0.57-0.89), Q4: 0.67 (0.54-0.84)]. For the AMI social score, only the Q4 group showed reduced OR for sarcopenia [0.79 (0.62-1.01)]. Q3 and Q4 of the AMI total score and physical score were associated with reduced OR of all sarcopenia indices (aOR 0.55-0.82, all P < 0.05), whereas Q4 of AMI social score was associated with all indices (aOR 0.85-0.81, all P < 0.05).
CONCLUSIONS: The extent of life space with physical activity was associated with sarcopenia in community-dwelling older adults. A longitudinal study is needed to examine whether life space with physical and social activities affect the development of sarcopenia.

Keywords:  Life space; Musculoskeletal disease; Physical activity; Social activity

DOI:  https://doi.org/10.1002/jcsm.12994
J Cachexia Sarcopenia Muscle. 2022 Apr 17.

Autophagy in muscle regeneration: potential therapies for myopathies.

Wei Chen, Yushi Chen, Yuxi Liu, Xinxia Wang.

  Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Its biological functions include metabolic stress adaptation, stem cell differentiation, immunomodulation and diseases regulation, and so on. Current researches have proved that autophagy dysfunction may contribute to the pathogenesis of some myopathies through impairment of myofibres regeneration. Studies of autophagy inhibition also indicate the importance of autophagy in muscle regeneration, while activation of autophagy can restore muscle function in some myopathies. In this review, we aim to report the mechanisms of action of autophagy on muscle regeneration to provide relevant references for the treatment of regenerating defective myopathies by regulating autophagy. Results have shown that one key mechanism of autophagy regulating the muscle regeneration is to affect the differentiation fate of muscle stem cells (MuSCs), including quiescence maintenance, activation and differentiation. The roles of autophagy (organelle/protein degradation, energy facilitation, and/or other) vary at different myogenic stages of the repair process. When the muscle is in homeostasis, basal autophagy can maintain the quiescence state and stemness of MuSCs by renewing organelle and protein. After injury, the increased autophagy flux contributes to meet biological energy demand of MuSCs during activation and proliferation. By mitochondrial remodelling, autophagy during differentiation can promote the metabolic transformation and balance mitochondrial-mediated apoptosis signals in myoblasts. Autophagy in mature myofibres is also essential for the degradation of necrotic myofibres, and may affect the dynamics of MuSCs by affecting the secretion spectrum of myofibres or the recruitment of supporting cells. Except for myogenic cells, autophagy also plays an important role in regulating the function of non-myogenic cells in the muscle microenvironment, which is also essential for successful muscle recovery. Autophagy can regulate the immune microenvironment during muscle regeneration through the recruitment and polarization of macrophages, while autophagy in endothelial cells can regulate muscle regeneration in an angiogenic or angiogenesis-independent manner. Drug or nutrition targeted autophagy has been preliminarily proved to restore muscle function in myopathies by promoting muscle regeneration, and further understanding the role and mechanism of autophagy in various cell types during muscle regeneration will enable more effective combinatorial therapeutic strategies.

Keywords:  Autophagy; Microenvironment; MuSCs; Myopathies; Regeneration; Skeletal muscle

DOI:  https://doi.org/10.1002/jcsm.13000
Int J Environ Res Public Health. 2022 Apr 14. pii: 4765. [Epub ahead of print]19(8):

Interventions to Improve Body Composition, Upper and Lower Extremity Muscle Strength, and Balance Ability of Older Female Adults: An Intervention Study.

Wei-Yang Huang, Cheng-En Wu.

  The aim of the present study was to understand the effects of a moderate-intensity physical activity program on the changes observed in the body composition, upper and lower extremity muscle strength, as well as balance in elderly female adults in order to evaluate sarcopenia. In this study, 30 healthy elderly females were recruited and were randomly assigned to either the control group or the experimental group. The experimental group engaged in a moderate-intensity physical activity program twice a week for 8 weeks. Using a body composition analyzer, the senior fitness test, and handgrip strength and gait speed tests, all participants were tested in pre- and post-tests. The results of the study revealed changes in the overall body composition in the experimental group, with significant decreases in body mass index, body fat percentage, and body fat mass and substantial increases in the basal metabolic rate and skeletal muscle mass, while the upper and lower extremity muscle strength and balance ability also showed significant improvements. The moderate-intensity physical activity program also increased upper limb handgrip strength and lower limb gait speed, showing that the plan was able to effectively evaluate sarcopenia. The study concluded that using upper limb handgrip strength and lower limb walking speed to evaluate sarcopenia are useful diagnostic tools. Moderate-intensity physical activity is effective for improving muscle strength and reducing sarcopenia.

Keywords:  body composition; elderly female; interventions; moderate-intensity physical activity; sarcopenia

DOI:  https://doi.org/10.3390/ijerph19084765
Clin Nutr. 2022 Mar 31. pii: S0261-5614(22)00106-6. [Epub ahead of print]41(5): 1131-1140

Association between sarcopenia and clinical outcomes in chronic kidney disease patients: A systematic review and meta-analysis.

Heitor S Ribeiro, Silvia G R Neri, Juliana S Oliveira, Paul N Bennett, João L Viana, Ricardo M Lima.

   BACKGROUND & AIMS: Sarcopenia is a risk factor for adverse outcomes in older adults, but this has yet to be confirmed in chronic kidney disease (CKD). We conducted a systematic review to investigate the association between sarcopenia and its traits with mortality, hospitalization, and end-stage kidney disease (ESKD) progression in CKD patients.
METHODS: Five electronic databases were searched, including MEDLINE and Embase. Observational cohort studies with CKD patients were included. The sarcopenia traits assessed were low muscle strength, low muscle mass, and low physical performance, as well as diagnosed sarcopenia (combined low muscle mass and low strength/performance). Hazard ratios (HR), risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CI) were pooled using random-effect meta-analyses.
RESULTS: From a total of 4922 screened studies, 50 (72,347 patients) were included in the review and 38 (59,070 patients) in the meta-analyses. Most of the included studies were in dialysis patients (n = 36, 72%). Pooled analyses showed that low muscle strength (15 studies; HR:1.99; 95%CI:1.65 to 2.41; I2:45%), low muscle mass (20 studies; HR:1.51; 95%CI:1.36 to 1.68; I2:26%) and low physical performance (five studies; HR:2.09; 95%CI:1.68 to 2.59; I2:0%) were associated with increased mortality risk in CKD patients. Diagnosed sarcopenia was also associated with the mortality risk in dialysis patients (eight studies; HR:1.87; 95%CI:1.35 to 2.59; I2:40%). On the other hand, it was uncertain whether low muscle mass was associated with hospitalization (two studies in dialysis patients; RR:1.81; 95% CI:0.78 to 4.22; I2:59%). Further, limited ESKD progression measures prevented meta-analysis for this outcome.
CONCLUSIONS: Low muscle strength, low muscle mass, and low physical performance were associated with higher mortality in CKD patients. In dialysis patients, diagnosed sarcopenia also represented higher mortality risk. Evidence to conclude associations with hospitalization and ESKD progression is currently lacking.
PROSPERO REGISTRATION: CRD42020192198.

Keywords:  Body composition; Dialysis; Kidney failure; Muscle mass; Muscle strength; Physical performance

DOI:  https://doi.org/10.1016/j.clnu.2022.03.025
BMC Geriatr. 2022 Apr 18. 22(1): 335

Effect of semi-recumbent vibration exercise on muscle outcomes in older adults: a pilot randomized controlled clinical trial.

Murad H Taani, Neil Binkley, Ronald Gangnon, Diane Krueger, Bjoern Buehring.

   BACKGROUND: Many older adults with physical limitations living in residential care apartments are unable to exercise in a standing position and are at risk for declining in muscle function leading to falls and injury. Novel approaches to achieve exercise benefits are needed. The purpose of this study was to test the effect of semi-recumbent vibration exercise on muscle outcomes in older adults living in residential care apartment complexes (RCACs).
METHODS: A randomized, crossover design was used to examine the effect of semi-recumbent vibration exercise on muscle function and mass among 32 RCAC residents (mean age 87.5 years) with physical limitations. Participants received a randomized sequence of two study conditions: sham or vibration for 8 weeks each separated by a 4-week washout. Before and after the 8 weeks of vibration treatment and sham treatment, muscle mechanography was used to assess muscle function including jump power, weight-corrected jump power, and jump height. Short physical performance battery (SPPB) and handgrip strength were also used to measure muscle function. Bioelectrical impedance spectroscopy was used to estimate skeletal muscle mass. The effect of the vibration treatment on muscle outcomes was analyzed through mixed effects linear regression models.
RESULTS: Vibration exercise leads to better jump height (p < .05) compared to sham exercise but also poorer chair rise performance (p = 0.012). Other muscle functions tests and muscle mass parameters showed non-significant changes.
CONCLUSION: This small pilot study showed no conclusive results on the effect of semi-recumbent vibration exercise on muscle function and mass in older adults living in RCAC. However, the promising signals of improved jump performance could be used to power larger studies of longer duration with various vibration doses to determine the benefit of vibration exercise in this physically impaired, high-risk population with few exercise capabilities.
TRIAL REGISTRATION: The study is registered at clinicaltrials.gov ( NCT02533063 ; date of first registration 26/08/2015).

Keywords:  Exercise; Jump power; Muscle function; Residential care apartment complexes

DOI:  https://doi.org/10.1186/s12877-022-03052-0
Front Aging Neurosci. 2022 ;14 863901

Effects of the FNDC5/Irisin on Elderly Dementia and Cognitive Impairment.

Jin Peng, Jinhui Wu.

  Population aging is an inevitable problem nowadays, and the elderly are going through a lot of geriatric symptoms, especially cognitive impairment. Irisin, an exercise-stimulating cleaved product from transmembrane fibronectin type III domain-containing protein 5 (FNDC5), has been linked with favorable effects on many metabolic diseases. Recently, mounting studies also highlighted the neuroprotective effects of irisin on dementia. The current evidence remains uncertain, and few clinical trials have been undertaken to limit its clinical practice. Therefore, we provided an overview of current scientific knowledge focusing on the preventive mechanisms of irisin on senile cognitive decline and dementia, in terms of the possible connections between irisin and neurogenesis, neuroinflammation, oxidative stress, and dementia-related diseases. This study summarized the recent advances and ongoing studies, aiming to provide a better scope into the effectiveness of irisin on dementia progression, as well as a mediator of muscle brain cross talk to provide theoretical support for exercise therapy for patients with dementia. Whether irisin is a diagnostic or prognostic factor for dementia needs more researches.

Keywords:  BDNF; dementia; inflammation; irisin; muscle brain cross talk; oxidative stress

DOI:  https://doi.org/10.3389/fnagi.2022.863901
Int J Environ Res Public Health. 2022 Apr 14. pii: 4723. [Epub ahead of print]19(8):

Longitudinal Association between Sarcopenia and Cognitive Impairment among Older Adults in Rural Malaysia.

K Ramoo, Noran N Hairi, A Yahya, W Y Choo, F Mohd Hairi, D Peramalah, S Kandiben, A Bulgiba, Z Mohd Ali, I Abdul Razak, N Ismail, N S Ahmad.

  Sarcopenia is a condition that is highly prevalent among older adults. This condition is linked to numerous adverse health outcomes, including cognitive impairment that impairs healthy ageing. While sarcopenia and cognitive impairment may share a common pathway, limited longitudinal studies exist to show the relationship between these two conditions. Therefore, this study aimed to examine the longitudinal association between sarcopenia and cognitive impairment. This is a cohort study among older adults residing in Kuala Pilah District, Negeri Sembilan, Malaysia. There were 2404 respondents at the baseline and 1946 respondents at one-year follow-up. Cognitive impairment was determined using Mini-mental State Examination scores. Sarcopenia was identified using the Asian Working Group for Sarcopenia 2019 criteria, gait speed was measured using a 4-meter gait test, handgrip strength was assessed using Jamar handheld dynamometer, and appendicular skeletal muscle mass was measured using bioelectrical impedance analysis. Generalized estimating equation (GEE) was used to determine the longitudinal association between sarcopenia and cognitive impairment, presented as relative risk (RR) and its 95% confidence interval. The prevalence of sarcopenia was 5.0% (95% CI 4.00-5.90), and severe sarcopenia was 3.60% (95% CI 2.84-4.31). Upon adjusting for covariates, older adults with sarcopenia have an 80 per cent increased risk of cognitive impairment compared to those without (RR 1.80; 95% CI 1.18-2.75). Similarly, severe sarcopenia was found to significantly increase the risk of cognitive impairment by 101 per cent in the adjusted model (RR 2.01; 95% CI 1.24-3.27). Our study showed that sarcopenia, severe sarcopenia, low physical activity, depressive symptoms, hearing impairment and chronic pain were associated with a higher risk of cognitive impairment among community-dwelling older adults. Therefore, early intervention to prevent sarcopenia, depressive symptoms, hearing impairment, chronic pain, and higher physical activity among older adults is recommended.

Keywords:  cognitive impairment; older adults; sarcopenia

DOI:  https://doi.org/10.3390/ijerph19084723
HIV Med. 2022 Apr 19.

Frailty and sarcopenia among Turkish people aged 40 and above living with HIV.

Mehdi Houssein, Ahmet Çagkan Inkaya, Cafer Balci, Mert Esme, Meliha Çağla Sönmezer, Serhat Unal, Meltem Gülhan Halil.

   BACKGROUND: People living with HIV face a variety of challenges, including accelerated ageing and geriatric syndromes. In this study, we aimed to examine the prevalence of frailty and sarcopenia among Turkish people living with HIV.
METHODS: In total, 100 people living with HIV were recruited in this study. Frailty was determined using Fried's frailty phenotype, and we calculated the Charlson Comorbidity Index, Veterans Aging Cohort Study (VACS) index, fracture risk assessment tool scores, and Mini-Mental State Exam scores. We determined muscle mass using bioelectric impedance analysis, gastrocnemius muscle thickness using ultrasonography, and muscle strength using handgrip strength.
RESULTS: The mean ± standard deviation age was 50.0 ± 8.3 years. In total, 11% of the patients were frail. The risk of comorbidity and mortality, VACS index, and 5-year mortality risk was significantly higher in the frail group, as was sarcopenia. Fat-free muscle mass and handgrip strength were correlated with gastrocnemius muscle thickness. Gastrocnemius muscle thickness suggestive of sarcopenia was defined as 13.05 mm. The cognitive impairment rate was 5% and was associated with physical frailty.
CONCLUSION: Frailty is common and associated with higher morbidity and mortality rates among Turkish people living with HIV.

Keywords:  HIV; ageing; antiretroviral therapy; co-morbidities; frailty; sarcopenia

DOI:  https://doi.org/10.1111/hiv.13311
J Frailty Aging. 2022 ;11(2): 135-142

Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

M Cesari, R Bernabei, B Vellas, R A Fielding, D Rooks, D Azzolino, J Mariani, A A Oliva, S Bhasin, Y Rolland.

  Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.

Keywords:  Aging; clinical trial; frailty; pharmacological interventions; physical performance; sarcopenia

DOI:  https://doi.org/10.14283/jfa.2022.30
Antioxidants (Basel). 2022 Apr 06. pii: 725. [Epub ahead of print]11(4):

Identification of Coenzyme Q10 and Skeletal Muscle Protein Biomarkers as Potential Factors to Assist in the Diagnosis of Sarcopenia.

Chi-Hua Yen, Po-Sheng Chang, Yu-Hsun Chang, Ping-Ting Lin.

  The aim of this study was to explore the use of coenzyme Q10 and skeletal muscle protein biomarkers in the diagnosis of sarcopenia. Subjects with or without sarcopenia were recruited. The anthropometric, muscle strength and endurance measurements were assessed. Muscle proteins (albumin and creatine kinase), myokines (irisin and myostatin), and the coenzyme Q10 level were measured. Approximately half of the subjects suffered from a low coenzyme Q10 concentration (<0.5 μM). The levels of creatinine kinase and irisin were significantly lower in subjects with sarcopenia (p ≤ 0.05). In receiver operating characteristic analyses, irisin and creatine kinase showed a better prediction capability for sarcopenia (area under the curve, irisin: 0.64 vs. creatinine kinase: 0.61) than other biomarkers. Additionally, a low level of irisin (<118.0 ng/mL, odds ratio, 6.46, p < 0.01), creatine kinase (<69.5 U/L, odds ratio, 3.31, p = 0.04), or coenzyme Q10 (<0.67 μM, odds ratio, 9.79, p < 0.01) may increase the risk for sarcopenia even after adjusting for confounders. Since the levels of coenzyme Q10 and muscle biomarkers, such as irisin and creatine kinase, are associated with sarcopenia, we suggest they could be used as candidate markers to assist in the diagnosis of sarcopenia.

Keywords:  coenzyme Q10; diagnosis; myokines; sarcopenia; skeletal muscle protein biomarkers

DOI:  https://doi.org/10.3390/antiox11040725
Life (Basel). 2022 Apr 06. pii: 539. [Epub ahead of print]12(4):

P62/SQSTM1 beyond Autophagy: Physiological Role and Therapeutic Applications in Laboratory and Domestic Animals.

Maria Giovanna Sabbieti, Andrea Marchegiani, Albert A Sufianov, Vladimir L Gabai, Alexander Shneider, Dimitrios Agas.

  Inflammation is the preceding condition for the development of mild and severe pathological conditions, including various forms of osteopenia, cancer, metabolic syndromes, neurological disorders, atherosclerosis, cardiovascular, lung diseases, etc., in human and animals. The inflammatory status is induced by multifarious intracellular signaling cascades, where cytokines, chemokines, arachidonic acid metabolites, adhesion molecules, immune cells and other components foster a "slow burn" at a local or systemic level. Assuming that countering inflammation limits the development of inflammation-based diseases, a series of new side-effects-free therapies was assessed in experimental and domestic animals. Within the targets of the drug candidates for quenching inflammation, an archetypal autophagic gear, the p62/sqstm1 protein, has currently earned attention from researchers. Intracellular p62 has been recently coined as a multi-task tool associated with autophagy, bone remodeling, bone marrow integrity, cancer progression, and the maintenance of systemic homeostasis. Accordingly, p62 can act as an effective suppressor of inflamm-aging, reducing oxidative stress and proinflammatory signals. Such an operational schedule renders this protein an effective watchdog for degenerative diseases and cancer development in laboratory and pet animals. This review summarizes the current findings concerning p62 activities as a molecular hub for cell and tissues metabolism and in a variety of inflammatory diseases and other pathological conditions. It also specifically addresses the applications of exogenous p62 (DNA plasmid) as an anti-inflammatory and homeostatic regulator in the treatment of osteoporosis, metabolic syndrome, age-related macular degeneration and cancer in animals, and the possible application of p62 plasmid in other inflammation-associated diseases.

Keywords:  aging; degenerative diseases; inflammation; inflammatory diseases; p62/SQSTM1

DOI:  https://doi.org/10.3390/life12040539
Antioxidants (Basel). 2022 Mar 31. pii: 692. [Epub ahead of print]11(4):

Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer's Disease.

John O Onukwufor, Robert T Dirksen, Andrew P Wojtovich.

  Alzheimer's disease (AD) is a devastating progressive neurodegenerative disease characterized by neuronal dysfunction, and decreased memory and cognitive function. Iron is critical for neuronal activity, neurotransmitter biosynthesis, and energy homeostasis. Iron accumulation occurs in AD and results in neuronal dysfunction through activation of multifactorial mechanisms. Mitochondria generate energy and iron is a key co-factor required for: (1) ATP production by the electron transport chain, (2) heme protein biosynthesis and (3) iron-sulfur cluster formation. Disruptions in iron homeostasis result in mitochondrial dysfunction and energetic failure. Ferroptosis, a non-apoptotic iron-dependent form of cell death mediated by uncontrolled accumulation of reactive oxygen species and lipid peroxidation, is associated with AD and other neurodegenerative diseases. AD pathogenesis is complex with multiple diverse interacting players including Aβ-plaque formation, phosphorylated tau, and redox stress. Unfortunately, clinical trials in AD based on targeting these canonical hallmarks have been largely unsuccessful. Here, we review evidence linking iron dysregulation to AD and the potential for targeting ferroptosis as a therapeutic intervention for AD.

Keywords:  Alzheimer’s disease; ferroptosis; iron dysregulation; lipid peroxidation; mitochondrial dysfunction; neurodegeneration; reactive oxygen species

DOI:  https://doi.org/10.3390/antiox11040692