4.7 Article

Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity

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OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/gly261

关键词

Adipose stem cells; Telomerase enzyme; Klotho; Antiaging genes; Telomere; CD90; Cycloastragenol; Pluripotency

资金

  1. National Institute of Health (NIH), USA
  2. NIH [R01 HL118558, DK093403, HL122166, HL116863, AG049780]

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Understanding the effect of molecular pathways involved in the age-dependent deterioration of stem cell function is critical for developing new therapies. The overexpression of Klotho (KL), an antiaging protein, causes treated animal models to enjoy extended life spans. Now, the question stands: Does KL deficiency accelerate stem cell aging and telomere shortening? If so, what are the specific mechanisms by which it does this, and is cycloastragenol (CAG) treatment enough to restore telomerase activity in aged stem cells? We found that KL deficiency diminished telomerase activity by altering the expression of TERF1 and TERT, causing impaired differentiation potential, pluripotency, cellular senescence, and apoptosis in stem cells. Telomerase activity decreased with KL-siRNA knockdown. This suggests that both KL and telomeres regulate the stem cell aging process through telomerase subunits TERF1, POT1, and TERT using the TGF beta, Insulin, and Wnt signaling. These pathways can rejuvenate stem cell populations in a CD90-dependent mechanism. Stem cell dysfunctions were largely provoked by KL deficiency and telomere shortening, owing to altered expression of TERF1, TGF beta 1, CD90, POT1, TERT, and basic fibroblast growth factor (bFGF). The CAG treatment partially rescued telomerase deterioration, suggesting that KL plays a critical role in life-extension by regulating telomere length and telomerase activity.

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Zehra, A. Zeyra, Z. Zhagniyev, L. G. Zhukova, M. Zivanovic, J. Zmuc, M. Zope, A. Zubayraeva, B. Zucker

Summary: The COVID-19 pandemic has significantly impacted global surgical practice, posing various challenges for surgeons worldwide. However, collaborative efforts by global surgical multidisciplinary teams are underway to address these challenges and explore the future of surgery post-COVID-19, emphasizing the need for establishing multidisciplinary ethics committees and fostering innovative leadership and collaboration.

BRITISH JOURNAL OF SURGERY (2021)

Article Medicine, General & Internal

Fallopian Tube Torsion Secondary to Paraovarian Fimbrial Cyst: A Difficult to Diagnose and a Rare Cause of Acute Abdomen in Adolescent

Shamail Syed, Ayesha Amin, Muneeb Ullah

Summary: Fallopian tube torsion secondary to paraovarian or paratubal cyst is a rare gynecological cause of acute abdomen, with no distinctive signs or characteristic features on radiological imaging. While paraovarian cysts are usually asymptomatic, they can sometimes lead to torsion of the fallopian tube, requiring surgical intervention to prevent complications.

CUREUS JOURNAL OF MEDICAL SCIENCE (2021)

Article Medicine, General & Internal

Management of Closed Tibal Shaft Fractures with Reamed Interlocking Nail

Shakeel Ahmad Shah, Muhammad Shoaib Zardad, Abdus Saboor, Imtiaz Muhammad, Maaz Ullah

Summary: The study confirmed the effectiveness and safety of reamed interlocking nail in the management of closed tibial shaft fractures, with an overall union rate of 93.75% and lower morbidity among cases demonstrated.

PAKISTAN JOURNAL OF MEDICAL & HEALTH SCIENCES (2021)

Article Medicine, General & Internal

Supracondylar Fracture of Humerus in Children Treated with Closed Reduction and Percutaneous Cross Pinning VS Lateral Pinning

Muhammad Shoaib Zardad, Shakeel Ahmad Shah, Muhammad Younas, Maaz Ullah, Imtiaz Muhammad, Kamran Asghar

Summary: This study compared the outcomes of percutaneous cross pinning and two lateral pinning in the treatment of closed reduction supracondylar fracture of humerus in children. The results showed that both techniques are safe and effective, with no significant difference in outcomes observed between the two groups.

PAKISTAN JOURNAL OF MEDICAL & HEALTH SCIENCES (2021)

Article Medicine, General & Internal

Determine the Mean Duration of Union in Femoral Shaft Fracture in Children Treated with Elastic Intra-Medullary Nailing

Muhammad Shoaib Zardad, Muhammad Younas, Shakeel Ahmad Shah, Imtiaz Muhammad, Maaz Ullah, Atif Hussain

Summary: The study aimed to evaluate the outcomes and union duration of femoral shaft fractures in children treated with elastic intramedullary nailing, demonstrating that this treatment modality is safe and effective with majority of patients achieving excellent functional results.

PAKISTAN JOURNAL OF MEDICAL & HEALTH SCIENCES (2021)

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