scholarly journals Interventional Strategies to Delay Aging-Related Dysfunctions of the Musculoskeletal System

2021 ◽  
Author(s):  
Naomasa Fukase ◽  
Ingrid K. Stake ◽  
Yoichi Murata ◽  
William S. Hambright ◽  
Sudheer Ravuri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Musculoskeletal System ◽  
Healthy Aging ◽  
Mtor Inhibitors ◽  
Negative Regulator ◽  
Musculoskeletal Tissue ◽  
Musculoskeletal Tissues ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Approaches

Aging affects bones, cartilage, muscles, and other connective tissue in the musculoskeletal system, leading to numerous age-related pathologies including osteoporosis, osteoarthritis, and sarcopenia. Understanding healthy aging may therefore open new therapeutic targets, thereby leading to the development of novel approaches to prevent several age-related orthopaedic diseases. It is well recognized that aging-related stem cell depletion and dysfunction leads to reduced regenerative capacity in various musculoskeletal tissues. However, more recent evidence suggests that dysregulated autophagy and cellular senescence might be fundamental mechanisms associated with aging-related musculoskeletal decline. The mammalian/mechanical target of Rapamycin (mTOR) is known to be an essential negative regulator of autophagy, and its inhibition has been demonstrated to promote longevity in numerous species. Besides, several reports demonstrate that selective elimination of senescent cells and their cognate Senescence-Associated Secretory Phenotype (SASP) can mitigate musculoskeletal tissue decline. Therefore, senolytic drugs/agents that can specifically target senescent cells, may offer a novel therapeutic strategy to treat a litany of age-related orthopaedic conditions. This chapter focuses on osteoarthritis and osteoporosis, very common debilitating orthopaedic conditions, and reviews current concepts highlighting new therapeutic strategies, including the mTOR inhibitors, senolytic agents, and mesenchymal stem cell (MSC)-based therapies.

scholarly journals Musculoskeletal Regenerative Engineering: Biomaterials, Structures, and Small Molecules

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Roshan James ◽  
Cato T. Laurencin
Keyword(s):  
Stem Cell ◽  
Materials Science ◽  
Musculoskeletal Tissue ◽  
Tissue Repair And Regeneration ◽  
Musculoskeletal Tissues ◽  
Organ Regeneration ◽  
Organ Systems ◽  
Cell Niche ◽  
Stem Cell Science ◽  
Advanced Biomaterials

Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to re-engineer/guide stem cells to yield the desired organ cells and tissues. Tissue engineering strategies were ideally suited to repair damaged tissues; however, the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems integrated into a single phase require more than optimal combinations of biomaterials and biologics. We highlight bioinspired advancements leading to novel regenerative scaffolds especially for musculoskeletal tissue repair and regeneration. Tissue and organ regeneration relies on the spatial and temporal control of biophysical and biochemical cues, including soluble molecules, cell-cell contacts, cell-extracellular matrix contacts, and physical forces. Strategies that recapitulate the complexity of the local microenvironment of the tissue and the stem cell niche play a crucial role in regulating cell self-renewal and differentiation. Biomaterials and scaffolds based on biomimicry of the native tissue will enable convergence of the advances in materials science, the advances in stem cell science, and our understanding of developmental biology.

Prevalence of cognitive impairment in patients with hematologic cancers preceding stem cell transplantation: Program for healthy aging.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 32-32 ◽  
Author(s):  
Beatrice Jara-Almonte Edwards ◽  
Holly Michelle Holmes ◽  
Heather Valladarez ◽  
Ming Sun ◽  
Peter Khalil ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cognitive Impairment ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Functional Impairment ◽  
Cognitive Assessment ◽  
Healthy Aging ◽  
Early Stage ◽  
Cohort Analysis ◽  
Age Related

32 Background: Older adults, 65 years of age and older, with hematologic cancers may be at higher risk for cognitive impairment. It is postulated that the etiology of cognitive impairment in cancer may a combination of age-related and chemotherapy related cognitive impairment. Methods: We conducted a retrospective cohort analysis, of older adult patients 65 years and older evaluated at the Program for Healthy Aging at MD Anderson from January 1, 2013 through March 31, 2015. Cognitive assessment was evaluated through personal interview, and the Montreal cognitive assessment, functional assessment utilizing ADLs and IADLs. Screening for depression was conducted with the PHQ-9. Patients were interviewed regarding risk factors for dementia including depression, concussions, alcohol abuse, and family history of dementia. Level of education was assessed. Patients were euthymic. Cognitive impairment was defined as an abnormal MOCA without functional impairment, dementia was defined as an abnormal MOCA with functional impairment. Imaging and assessment for reversible factors of memory loss was conducted. SAS 9.4 (SAS Institute INC, Cary, NC) was used for data analysis. Results: The majority of these 62 patients had received chemotherapy for more than 2 years. Cognitive impairment and/or dementia were identified in 50 (80.6%) patients. Types of dementia included Alzheimer’s disease (n = 4, 8%), vascular dementia (n = 5, 10 %), and mixed dementia (n = 15, 30%).Mild cognitive impairment was evidenced in 14 cases (28%) The majority of cases of dementia with known stage were early stage dementia (n = 13, 72.2%), moderate stage dementia (n = 3, 16.7%), and advanced or severe dementia (n = 2, 11.1%). Brain imaging was performed identifying white matter microischemic changes, cerebrovascular accidents and brain atrophy in some cases. No significant thyroid abnormalities, B12 deficiency or other reversible causes were identified. Conclusions: Cognitive impairment and dementia are prevalent in older patients with hematologic malignancies. Identification and management of this condition may prevent delirium and hospital complications during stem cell transplantation.

scholarly journals 15-PGDH as a Negative Regulator of Age-Related Organ Fitness

2020 ◽  
Author(s):  
Won Jin Ho ◽  
Julianne N.P. Smith ◽  
Young Soo Park ◽  
Matthew Hadiono ◽  
Kelsey Christo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tissue Injury ◽  
Peripheral Blood Cell ◽  
Multiple Organ ◽  
Negative Regulator ◽  
Post Transplantation ◽  
Aged Mice ◽  
Cell Counts ◽  
Age Related ◽  
Organ Systems

ABSTRACTEmerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cell regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss of Hpgd expression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness.ARTICLE SUMMARY15-PGDH as a Driver of Age-Related Tissue Dysfunction

scholarly journals Herb-Derived Products: Natural Tools to Delay and Counteract Stem Cell Senescence

2020 ◽  
Vol 2020 ◽  
pp. 1-28
Author(s):  
Provvidenza M. Abruzzo ◽  
Silvia Canaider ◽  
Valeria Pizzuti ◽  
Luca Pampanella ◽  
Raffaella Casadei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Cell Senescence ◽  
Self Renewal ◽  
Diminished Capacity ◽  
Age Related ◽  
Secretory Phenotype

Cellular senescence plays a very important role in organismal aging increasing with age and in age-related diseases (ARDs). This process involves physiological, structural, biochemical, and molecular changes of cells, leading to a characteristic trait referred to “senescence-associated secretory phenotype (SASP).” In particular, with aging, stem cells (SCs) in situ exhibit a diminished capacity of self-renewal and show a decline in their functionality. The identification of interventions able to prevent the accumulation of senescent SCs in the organism or to pretreat cultured multipotent mesenchymal stromal cells (MSCs) prior to employing them for cell therapy is a main purpose of medical research. Many approaches have been investigated and resulted effective to prevent or counteract SC senescence in humans, as well as other animal models. In this work, we have reviewed the chance of using a number of herb-derived products as novel tools in the treatment of cell senescence, highlighting the efficacy of these agents, often still far from being clearly understood.

scholarly journals Stem Cell Quiescence versus Senescence: The Key for Healthy Aging

2021 ◽  
Vol 13 (4) ◽  
pp. 337-49
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Adult Stem Cell ◽  
Cell Aging ◽  
Tissue Specific ◽  
Age Related ◽  
Cell Decline ◽  
Tissue Specific Stem Cells

BACKGROUND: Aging tissues lose their homeostatic and regenerative capacities, which has been linked to the degeneration of the stem cells such as the tissue-specific stem cells, the stem cell niches, and systemic cues that regulate stem cell activity.CONTENT: The maintenance of tissue homeostatic and regeneration dependent on its tissue-specific stem cells, that —long-lived cells with the ability to self-renew and differentiate into mature cells. Understanding the molecular mechanisms that governs stem cell survival, self-renewal, quiescence, proliferation, and commitment to specific differentiated cell lineages is critical for identifying the drivers and effectors of age-associated stem cell failure. Such understanding will be critical for the development of therapeutic approaches that can decrease, and possibly reverse and repair the age-related degenerative process in aging tissues.SUMMARY: The exact mechanisms and reasons of aging process were not fully elucidated until now. Stem cells is one of the keys for maintaining tissues heath and understanding how stem cell decline with age will give us opportunities to find strategy in increasing somatic stem cells regenerative capacity and delay the aging process.KEYWORDS: adult stem cell, aging, epigenetic, metabolism, quiescence, senescence

scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

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