Age-Related Changes in Tissue-Specific Stem Cells.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. sci-3-sci-3
Author(s):  
Amy J. Wagers ◽  
Massimiliano Cerletti ◽  
Shane R. Mayack ◽  
Francis S. Kim ◽  
Jennifer L. Shadrach
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Bone Marrow Failure ◽  
Cell Activity ◽  
Older Individuals ◽  
Extrinsic Factors ◽  
Tissue Specific ◽  
Age Related ◽  
Tissue Specific Stem Cells

Abstract Aging of multicellular organisms typically involves progressive decline in the body’s ability to maintain homeostatic cell replacement and to regenerate tissues and organs after injury. In both the blood and the skeletal muscle, aging significantly impairs regenerative activity and can dysregulate normal homeostatic production of mature cells. These age-acquired defects in tissue function profoundly impact the health of older individuals, as evidenced by the high incidence of age-related muscle deterioration (sarcopenia), bone marrow failure, immune dysfunction, and blood cancers in the elderly. How aging causes deterioration of tissue function is poorly understood, but several lines of evidence suggest that loss or functional impairment of tissue-specific stem cells directly contributes to age-dependent failures in tissue repair. Interestingly, the effects of aging on tissue stem cell function appear to arise at least in part from alterations in the aged tissue environment, which can inhibit stem cell activity in older animals and may be regulated by factors that circulate naturally in the bloodstream. By making use of sensitive in vivo and in vitro approaches, including direct cell isolation by FACS, we are investigating the extrinsic factors and interactions that control stem cell function in aged animals. Our current studies have pointed us toward a discrete set of metabolic regulators and inflammatory cytokines, which may alter the signals that stem cells receive from their environment in aged animals. The knowledge we gain from these ongoing studies will help to define novel strategies to delay or reverse the onset of age-related disease, extending the healthful life of aging individuals.

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 Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Proliferative Potential ◽  
True Nature ◽  
Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

scholarly journals Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao Sheng ◽  
Yuedan Zhu ◽  
Juanyu Zhou ◽  
La Yan ◽  
Gang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caffeic Acid ◽  
Stress Responses ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Cell Aging ◽  
Positive Effects ◽  
Age Related ◽  
Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

Aging and immune response to exercise

1998 ◽  
Vol 76 (5) ◽  
pp. 562-572 ◽  
Author(s):  
Shoji Shinkai ◽  
Masamitsu Konishi ◽  
Roy J Shephard
Keyword(s):  
Cellular Immunity ◽  
Acute Exercise ◽  
Cell Function ◽  
Nk Cell ◽  
Cell Activity ◽  
The Elderly ◽  
Strenuous Exercise ◽  
Elderly Subjects ◽  
Older Individuals ◽  
Age Related

Human immune function undergoes adverse changes with aging. The T cells, which have a central role in cellular immunity, show the largest age-related differences in distribution and function, with thymus involution as the apparent underlying cause. The immune responses to acute exercise and training have not been studied extensively in the elderly. The natural killer (NK) cell response to a single exercise challenge is normal in older individuals, but immediately after exercise the elderly subjects manifest less suppression of phytohemagglutinin (PHA)-induced lymphocyte proliferation than younger individuals. In contrast, a strenuous exercise seems to induce a more sustained postexercise suppression of cellular immunity in older individuals than in their young peers. A few cross-sectional comparisons of immune status between physically fit elderly individuals and young sedentary controls suggest that habitual physical activity may enhance NK cell activity, checking certain aspects of the age-related decline in T cell function, such as reduced mitogenesis in response to plant lectins and decreases in the production of certain types of cytokine. The clinical implications, however, remain to be clarified by future study.Key words: immune senescence, innate immunity, adaptive immunity.

Antioxidant Treatment Rescues An Accelerated Aging Phenotype In Dyskerin Mutated Bone Marrow Stem Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2614-2614
Author(s):  
Baiwei Gu ◽  
Jian-meng Fan ◽  
Monica Bessler ◽  
Philip J Mason
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Function ◽  
Bone Marrow Failure ◽  
Dyskeratosis Congenita ◽  
Untreated Group ◽  
Telomere Maintenance ◽  
Antioxidant Treatment ◽  
Transplantation Experiments

Abstract Abstract 2614 X-linked Dyskeratosis Congenita (DC) is due to mutations in the DKC1 gene, which encodes the protein dyskerin. Dyskerin is a highly conserved nucleolar protein that, as part of a specialized nucleolar RNP, catalyzes the pseudouridylation of specific residues in newly synthesized ribosomal RNAs and spliceosomal snRNAs. Dyskerin also associates with telomerase and is involved in telomere maintenance. In addition to the well known effect of telomere homeostasis on cancer, it is evident that telomere maintenance may also be important in replicative aging because of telomere shortening due to the limited expression of telomerase activity in dividing somatic cells. Accumulating evidence suggests that dysfunctional telomeres resulting in premature cellular senescence is the primary cause of bone marrow failure in dyskeratosis congenita. It is important to determine the mechanism whereby Dkc1 mutations lead to premature cellular senescence in bone marrow. We have produced a line of mice containing a mutation, Dkc1Δ15, which is a copy of a pathogenic human mutation. Male Dkc1Δ15 mice showed a decrease in the proportion of B and T lymphocytes in peripheral blood and reduced body weight with age but no overt bone marrow failure syndrome phenotypes. Our previous competitive bone marrow transplantation experiments showed that the Dkc1Δ15 mutation caused decay of stem cell function with age. Bone marrow from older Dkc1Δ15 mice was markedly inefficient in repopulation studies compared with bone marrow from age matched wild type mice. We also found that N-acetyl cysteine (NAC) could at least partially rescue the growth disadvantage of dyskerin mutant spleen cells or fibroblasts which was associated with accumulation of DNA damage and reactive oxygen species. To determine if NAC, or other antioxidants might be useful therapeutically it is important to determine their effects on stem cell function, which is defective in DC. To this end we established a cohort of mice that were given NAC in their drinking water (1mg/ml) from 3-weeks of age and maintained on NAC for 1 year. We found that long term NAC treatment did not show significant side effects on the mice. They had slightly increased neutrophils, but no difference in life span and body weight compared with the untreated group. Impressively, old male Dkc1Δ15 mice showed corrected B and T cell proportions in peripheral blood after treatment with NAC. Competitive bone marrow transplantation experiments were carried out in which a 1:1 mixture of BM cells from mutant and WT mice was used to repopulated lethally irradiated recipient mice. These experiments showed that, when taken from NAC treated animals, old Dkc1Δ15 BM cells could compete with age matched WT cells with 40–45% of Dkc1Δ15 cells in primary recipients compared with only 20% for the untreated group. Moreover, after secondary transplantation, cells from the NAC treated group still represent 15–20% of Dkc1Δ15 cells in recipients while those from the untreated group could not be detected. These results strongly suggest that NAC treatment can partially restore the bone marrow repopulating ability of Dkc1Δ15 stem cells. Together with our previous results these data suggest that a pathogenic Dkc1 mutation, through its effect on telomerase, initiates stem cell aging before telomeres are short and that increased oxidative stress might play a role in this process. Moreover the effects of the mutation may be prevented or delayed by antioxidant treatment, although the precise mechanism will be the subject of future investigation. Disclosures: Bessler: Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Taligen: Consultancy.

scholarly journals Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?

Biology Open ◽  
2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Aaron M. Savage ◽  
Ramiro Alberio ◽  
Andrew D. Johnson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Germ Plasm ◽  
Cell Types ◽  
Model Organisms ◽  
Developmental Potential ◽  
Tissue Specific ◽  
Tissue Specific Stem Cells

ABSTRACT In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine. However, recent efforts to produce fully functional tissue-specific stem cells have fallen short. One possible cause of shortcomings may be that model organisms used to characterize basic vertebrate embryology (Xenopus, zebrafish, chick) may employ molecular mechanisms for stem cell specification that are not conserved in humans, a prominent example being the specification of primordial germ cells (PGCs). Germ plasm irreversibly specifies PGCs in many models; however, it is not conserved in humans, which produce PGCs from tissue termed germline-competent mesoderm (GLCM). GLCM is not conserved in organisms containing germ plasm, or even in mice, but understanding its developmental potential could unlock successful production of other stem cell types. GLCM was first discovered in embryos from the axolotl and its conservation has since been demonstrated in pigs, which develop from a flat-disc embryo like humans. Together these findings suggest that GLCM is a conserved basal trait of vertebrate embryos. Moreover, the immortal nature of germ cells suggests that immortality is retained during GLCM specification; here we suggest that the demonstrated pluripotency of GLCM accounts for retention of immortality in somatic stem cell types as well. This article has an associated Future Leaders to Watch interview with the author of the paper.

scholarly journals Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

2015 ◽  
Vol 7 (2) ◽  
pp. 73
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Cell Function ◽  
Muscle Stem Cell ◽  
Muscle Aging ◽  
Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

scholarly journals Investigation of Stem Cell Aging Throughout the Lifetime and Therapeutic Opportunities

2020 ◽  
Author(s):  
Sarah Karimi ◽  
Setareh Raoufi ◽  
Zohreh Bagher
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Cell Function ◽  
Cell Activity ◽  
The Body ◽  
Natural Phenomenon ◽  
Cell Aging ◽  
Molecular Pathways ◽  
Stem Cell Aging

Introduction: Aging is a natural phenomenon that is caused by changes in the cells of the body. Theoretically, aging starts from birth and lasts throughout life. These changes affect the function of the cells. Also, in old tissues, the capacity for homeostasis and tissue repair is decline due to destructive changes in specific tissue stem cells, niche of stem cells and systemic factors that regulate stem cell activity. Understanding molecular pathways that disrupt stem cell function during aging is crucial for the development of new treatments for aging-associated diseases. In this article, the symptoms of stem cell aging and the key molecular pathways that are commonly used for the aging of stem cells were discussed. We will consider experimental evidence for all of the mechanisms and evaluate the way that can slow down or even stop the aging process. Finally, we will look at the aging process of three types of stem cells.

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