scholarly journals Necroptosis promotes the Aging of the Male Reproductive System in Mice

2017 ◽  
Author(s):  
Dianrong Li ◽  
Lingjun Meng ◽  
Tao Xu ◽  
Yaning Su ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Reproductive System ◽  
Accelerated Aging ◽  
Reproductive Organs ◽  
Male Reproductive System ◽  
Necrotic Cell Death ◽  
Wild Type ◽  
Necrotic Cell ◽  
Age Related ◽  
And Function ◽  
Age Related Changes

AbstractNecroptosis is a form of programmed necrotic cell death in mammals that is mediated by a pair of kinases, RIP1 and RIP3, as well as the RIP3 substrate MLKL. We report here that male reproductive organs of both RIP3-and MLKL-knockout mice retain “youthful” morphology and function into advanced age, while those of age-matched wild type mice deteriorate. The RIP3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild type mice. When the testes of young wild type mice are given a local necroptotic stimulus, their reproductive organs showed accelerated aging. Feeding of wild type mice with an RIP1 inhibitor prior to the normal onset of age-related changes in their reproductive organs blocked the appearance of signs of aging. Thus, necroptosis in testes promotes the aging-associated deterioration of the male reproductive system in mice.

scholarly journals RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Dianrong Li ◽  
Lingjun Meng ◽  
Tao Xu ◽  
Yaning Su ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Reproductive System ◽  
Accelerated Aging ◽  
Reproductive Organs ◽  
Male Reproductive System ◽  
Necrotic Cell Death ◽  
Wild Type ◽  
Necrotic Cell ◽  
Age Related ◽  
And Function ◽  
Age Related Changes

A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis. We report here that male reproductive organs of both Ripk3- and Mlkl-knockout mice retain ‘youthful’ morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. The RIPK3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild-type mice. When the testes of young wild-type mice are given a local necroptotic stimulus, their reproductive organs showed accelerated aging. Feeding of wild-type mice with an RIPK1 inhibitor prior to the normal onset of age-related changes in their reproductive organs blocked the appearance of signs of aging. Thus, necroptosis in testes promotes the aging-associated deterioration of the male reproductive system in mice.

scholarly journals Impact of Age on the Male Reproductive System from the Pathologist’s Perspective

2016 ◽  
Vol 45 (1) ◽  
pp. 195-205 ◽  
Author(s):  
Catherine A. Picut ◽  
Amera K. Remick
Keyword(s):  
Postnatal Development ◽  
Reproductive System ◽  
Reproductive Organs ◽  
Male Reproductive System ◽  
Laboratory Animals ◽  
Large Animal ◽  
Age Related ◽  
Organ Systems ◽  
Microscopic Evaluation ◽  
Tissue Changes

Age, and in particular young age, can significantly impact the response to toxicants in animals and can greatly influence the interpretation of tissue changes by the toxicologic pathologist. Although this applies to multiple organ systems, the current review focuses on the male reproductive system. When performing microscopic evaluation of male reproductive organs, the toxicologic pathologist must be aware of the dynamic changes in histomorphology, predominantly driven by timed hormonal alterations, at various life stages. Specific challenges pathologists face are understanding the appearance of male reproductive tissues throughout the neonatal, infantile, and juvenile developmental periods, recognizing when normal looks abnormal during tissue development, defining sexual maturity, and working with high interanimal variability in maturation rate and histologic appearance in developing large laboratory animals, such as nonhuman primates, dogs, and pigs. This review describes postnatal development of the male reproductive system in the rat, demonstrates how assessing toxicity during a defined window of postnatal development in the rat may improve definition of toxicant timing and targets, and discusses challenges associated with the interpretation of toxicity in immature large animal species. The emphasis is on key age-related characteristics that influence the interpretation of tissue changes by the toxicologic pathologist.

scholarly journals Toxicity Investigation of Nano-SiO2 on Male Reproductive System in Pubertal Mice

2021 ◽  
Author(s):  
Fanli Sun ◽  
Xuying Wang ◽  
Pinzheng Zhang ◽  
Ziyun Chen ◽  
Zhiyi Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reproductive System ◽  
Intraperitoneal Injection ◽  
Sperm Quality ◽  
Underlying Mechanism ◽  
Reproductive Organs ◽  
Male Reproductive System ◽  
Reproductive Capacity ◽  
Apoptotic Pathway ◽  
And Function

Abstract BackgroundPuberty is a crucial stage to gain reproductive capacity, but it is also a period vulnerable to exogenous materials. While exposure to nanoparticles (NPs) has been linked to toxic responses in reproductive system in previous findings, little is known about the age-dependent effect of NPs, let alone the underlying mechanism. In the present study, we assessed male fertility parameters and explored its mechanism following intraperitoneal exposure to Nano-Silicon dioxide (Nano-SiO2) in mice during puberty.Methods40 mice aged 5 weeks were divided into 2 groups after 1 week acclimation and then exposed to 40mg/kg Nano-SiO2 dissolved in saline or vehicle controls by intraperitoneal injection every day over a period of 7-day, respectively. Changes in the structure and function of male reproductive organs were detected after exposure.ResultsNano-SiO2 exposed through intraperitoneal injection could cause damage to the testicular and epididymal histological architecture and reduce the level of sex hormone (testosterone), leading to a decrease in sperm quality and quantity. Furthermore, Nano-SiO2 could induce oxidative stress and inflammation in male reproductive tissues, indicated by reduced activity of antioxidants (superoxide dismutase, SOD) and increased level of the lipid peroxidation marker (malondialdehyde, MDA), which leads to the activation of cell apoptosis.ConclusionExposure to Nano-SiO2 in pubertal mice could cause toxicity on male reproductive system via inducing oxidative stress and activating TNF-α mediated apoptotic pathway.

scholarly journals Physical activity in elderly

2015 ◽  
Vol 25 (4) ◽  
pp. 249 ◽  
Author(s):  
Jan Cvecka ◽  
Veronika Tirpakova ◽  
Milan Sedliak ◽  
Helmut Kern ◽  
Winfried Mayr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Electrical Stimulation ◽  
Muscle Mass ◽  
Irreversible Process ◽  
Significant Decline ◽  
Positive Effects ◽  
Age Related ◽  
And Performance ◽  
And Function ◽  
Age Related Changes

Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.

Age-Related Changes in Morphology and Function of Scapular Muscles in Asymptomatic People

PM&R ◽  
2017 ◽  
Vol 9 (9) ◽  
pp. 892-900 ◽  
Author(s):  
Shuhei Morise ◽  
Takayuki Muraki ◽  
Hiroaki Ishikawa ◽  
Shin-Ichi Izumi
Keyword(s):  
Age Related ◽  
And Function ◽  
Age Related Changes

scholarly journals Regenerative Medicine Approaches for Age-Related Muscle Loss and Sarcopenia: A Mini-Review

Gerontology ◽  
2017 ◽  
Vol 63 (6) ◽  
pp. 580-589 ◽  
Author(s):  
Juan Diego Naranjo ◽  
Jenna L. Dziki ◽  
Stephen F. Badylak
Keyword(s):  
Regenerative Medicine ◽  
Treatment Options ◽  
The Elderly ◽  
Signaling Molecules ◽  
Current Treatment ◽  
Muscle Physiology ◽  
Age Related ◽  
Increased Risk ◽  
And Function ◽  
Age Related Changes

Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein.

scholarly journals Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice

2018 ◽  
Vol 9 (1) ◽  
pp. 190-202 ◽  
Author(s):  
Leonidas Chouliaras ◽  
Roy Lardenoije ◽  
Gunter Kenis ◽  
Diego Mastroeni ◽  
Patrick R. Hof ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Dna Methylation ◽  
Brain Aging ◽  
Wild Type ◽  
Dna Hydroxymethylation ◽  
Quantitative Immunohistochemistry ◽  
Age Related ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Age Related Changes

Abstract Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer’s disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

White Adipose Tissue Depots in GHR−/− Mice: Age-Related Changes in Comparison to Wild-Type Controls

2011 ◽  
pp. P2-351-P2-351
Author(s):  
Lucila Sackmann Sala ◽  
Clare B Vesel ◽  
Ellen R Lubbers ◽  
Rachel D Munn ◽  
Katie M Troike ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Wild Type ◽  
Adipose Tissue Depots ◽  
Age Related ◽  
Age Related Changes

scholarly journals Age-Related Changes in Thymic Central Tolerance

2021 ◽  
Vol 12 ◽  
Author(s):  
Jayashree Srinivasan ◽  
Jessica N. Lancaster ◽  
Nandini Singarapu ◽  
Laura P. Hale ◽  
Lauren I. R. Ehrlich ◽  
...  
Keyword(s):  
T Cells ◽  
Negative Selection ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Adult Transition ◽  
Treg Function ◽  
Age Related ◽  
And Function ◽  
Antigen Presenting ◽  
Age Related Changes

Thymic epithelial cells (TECs) and hematopoietic antigen presenting cells (HAPCs) in the thymus microenvironment provide essential signals to self-reactive thymocytes that induce either negative selection or generation of regulatory T cells (Treg), both of which are required to establish and maintain central tolerance throughout life. HAPCs and TECs are comprised of multiple subsets that play distinct and overlapping roles in central tolerance. Changes that occur in the composition and function of TEC and HAPC subsets across the lifespan have potential consequences for central tolerance. In keeping with this possibility, there are age-associated changes in the cellular composition and function of T cells and Treg. This review summarizes changes in T cell and Treg function during the perinatal to adult transition and in the course of normal aging, and relates these changes to age-associated alterations in thymic HAPC and TEC subsets.

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