Metabolic Regulation of Stem Cells in Aging

AbstractPurpose of ReviewFrom invertebrates to vertebrates, the ability to sense nutrient availability is critical for survival. Complex organisms have evolved numerous signaling pathways to sense nutrients and dietary fluctuations, which influence many cellular processes. Although both overabundance and extreme depletion of nutrients can lead to deleterious effects, dietary restriction without malnutrition can increase lifespan and promote overall health in many model organisms. In this review, we focus on age-dependent changes in stem cell metabolism and dietary interventions used to modulate stem cell function in aging.Recent FindingsOver the last half-century, seminal studies have illustrated that dietary restriction confers beneficial effects on longevity in many model organisms. Many researchers have now turned to dissecting the molecular mechanisms by which these diets affect aging at the cellular level. One subpopulation of cells of particular interest are adult stem cells, the most regenerative cells of the body. It is generally accepted that the regenerative capacity of stem cells declines with age, and while the metabolic requirements of each vary across tissues, the ability of dietary interventions to influence stem cell function is striking.SummaryIn this review, we will focus primarily on how metabolism plays a role in adult stem cell homeostasis with respect to aging, with particular emphasis on intestinal stem cells while also touching on hematopoietic, skeletal muscle, and neural stem cells. We will also discuss key metabolic signaling pathways influenced by both dietary restriction and the aging process, and will examine their role in improving tissue homeostasis and lifespan. Understanding the mechanisms behind the metabolic needs of stem cells will help bridge the divide between a basic science interpretation of stem cell function and a whole-organism view of nutrition, thereby providing insight into potential dietary or therapeutic interventions.

Download Full-text

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

Biology Open ◽

10.1242/bio.058890 ◽

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.

Download Full-text

Investigation of Stem Cell Aging Throughout the Lifetime and Therapeutic Opportunities

Journal of Shahid Sadoughi University of Medical Sciences ◽

10.18502/ssu.v27i12.2837 ◽

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.

Download Full-text

Antheridial development in the moss Physcomitrella patens : implications for understanding stem cells in mosses

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0494 ◽

2017 ◽

Vol 373 (1739) ◽

pp. 20160494 ◽

Cited By ~ 8

Author(s):

Rumiko Kofuji ◽

Yasushi Yagita ◽

Takashi Murata ◽

Mitsuyasu Hasebe

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Molecular Mechanisms ◽

Physcomitrella Patens ◽

Evolutionary Relationship ◽

Terrestrial Ecosystem ◽

Cell Types ◽

Land Plant ◽

The Body ◽

New Type

Stem cells self-renew and produce precursor cells that differentiate to become specialized cell types. Land plants generate several types of stem cells that give rise to most organs of the plant body and whose characters determine the body organization. The moss Physcomitrella patens forms eight types of stem cells throughout its life cycle. Under gametangium-inducing conditions, multiple antheridium apical stem cells are formed at the tip of the gametophore and each antheridium apical stem cell divides to form an antheridium. We found that the gametophore apical stem cell, which typically forms leaf and stem tissues, changes to become a new type of stem cell, which we term the antheridium initial stem cell. This antheridium initial stem cell produces multiple antheridium apical stem cells, resulting in a cluster of antheridia at the tip of gametophore. This is the first report of a land plant stem cell directly producing another type of stem cell during normal development. Notably, the antheridium apical stem cells are distally produced from the antheridium initial stem cell, similar to the root cap stem cells of vascular plants, suggesting the use of similar molecular mechanisms and a possible evolutionary relationship. This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.

Download Full-text

The Role of MicroRNAs in Cardiac Stem Cells

Stem Cells International ◽

10.1155/2015/194894 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Nima Purvis ◽

Andrew Bahn ◽

Rajesh Katare

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Cell Function ◽

Cardiac Stem Cells ◽

Cell Therapies ◽

Small Noncoding Rna ◽

Proliferation And Differentiation

Stem cells are considered as the next generation drug treatment in patients with cardiovascular disease who are resistant to conventional treatment. Among several stem cells used in the clinical setting, cardiac stem cells (CSCs) which reside in the myocardium and epicardium of the heart have been shown to be an effective option for the source of stem cells. In normal circumstances, CSCs primarily function as a cell store to replace the physiologically depleted cardiovascular cells, while under the diseased condition they have been shown to experimentally regenerate the diseased myocardium. In spite of their major functional role, molecular mechanisms regulating the CSCs proliferation and differentiation are still unknown. MicroRNAs (miRs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Recent studies have demonstrated the important role of miRs in regulating stem cell proliferation and differentiation, as well as other physiological and pathological processes related to stem cell function. This review summarises the current understanding of the role of miRs in CSCs. A deeper understanding of the mechanisms by which miRs regulate CSCs may lead to advances in the mode of stem cell therapies for the treatment of cardiovascular diseases.

Download Full-text

Gastric Stem Cell and Cellular Origin of Cancer

Biomedicines ◽

10.3390/biomedicines6040100 ◽

2018 ◽

Vol 6 (4) ◽

pp. 100 ◽

Cited By ~ 9

Author(s):

Masahiro Hata ◽

Yoku Hayakawa ◽

Kazuhiko Koike

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Molecular Mechanisms ◽

Cell Function ◽

Stem Cell Markers ◽

Cell Markers ◽

Cellular Origin ◽

Cell Niche ◽

Stem Cell Populations ◽

G Protein Coupled

Several stem cell markers within the gastrointestinal epithelium have been identified in mice. One of the best characterized is Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) and evidence suggests that Lgr5+ cells in the gut are the origin of gastrointestinal cancers. Reserve or facultative stem or progenitor cells with the ability to convert to Lgr5+ cells following injury have also been identified. Unlike the intestine, where Lgr5+ cells at the crypt base act as active stem cells, the stomach may contain unique stem cell populations, since gastric Lgr5+ cells seem to behave as a reserve rather than active stem cells, both in the corpus and in the antral glands. Gastrointestinal stem cells are supported by a specific microenvironment, the stem cell niche, which also promotes tumorigenesis. This review focuses on stem cell markers in the gut and their supporting niche factors. It also discusses the molecular mechanisms that regulate stem cell function and tumorigenesis.

Download Full-text

Fundamental mechanisms of the stem cell regulation in land plants: lesson from shoot apical cells in bryophytes

Plant Molecular Biology ◽

10.1007/s11103-021-01126-y ◽

2021 ◽

Author(s):

Yuki Hata ◽

Junko Kyozuka

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Molecular Mechanisms ◽

Cell Function ◽

Chromatin Modification ◽

Land Plants ◽

Marchantia Polymorpha ◽

Cell Regulation ◽

Evolutionary Trajectory ◽

Stem Cell Regulation

Abstract Key message This review compares the molecular mechanisms of stem cell control in the shoot apical meristems of mosses and angiosperms and reveals the conserved features and evolution of plant stem cells. Abstract The establishment and maintenance of pluripotent stem cells in the shoot apical meristem (SAM) are key developmental processes in land plants including the most basal, bryophytes. Bryophytes, such as Physcomitrium (Physcomitrella) patens and Marchantia polymorpha, are emerging as attractive model species to study the conserved features and evolutionary processes in the mechanisms controlling stem cells. Recent studies using these model bryophyte species have started to uncover the similarities and differences in stem cell regulation between bryophytes and angiosperms. In this review, we summarize findings on stem cell function and its regulation focusing on different aspects including hormonal, genetic, and epigenetic control. Stem cell regulation through auxin, cytokinin, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) signaling and chromatin modification by Polycomb Repressive Complex 2 (PRC2) and PRC1 is well conserved. Several transcription factors crucial for SAM regulation in angiosperms are not involved in the regulation of the SAM in mosses, but similarities also exist. These findings provide insights into the evolutionary trajectory of the SAM and the fundamental mechanisms involved in stem cell regulation that are conserved across land plants.

Download Full-text

The Impact of Short-Term Dietary Restriction on Stem Cell Function

Innovation in Aging ◽

10.1093/geroni/igab046.443 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 116-117

Author(s):

Archana Unnikrishnan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Dietary Restriction ◽

Cell Function ◽

Aging Effects ◽

Short Term ◽

Regenerative Capacity ◽

Short Period ◽

The Impact ◽

Old Mice

Abstract Stem cells play a critical role in the maintenance of tissue function and their proliferative/regenerative capacity is essential to this role. Because stem cells persist over the lifespan of an animal, they are susceptible to gradual accumulation of age-associated damage, resulting in the loss of regenerative function that can impair organ function. Understanding the mechanism(s) that regulates stem cell function is essential for retarding the aging process, and stem cells are attractive targets for aging interventions. Dietary restriction (DR), the most robust anti-aging intervention to-date, has been shown to enhance the activity and integrity of stem cells in a variety of tissues (e.g., muscle, bone marrow, and intestine), and it is believed that effect of DR on stem cells plays an important role in the anti-aging action of DR. For example, DR has been shown to preserve and increase the number of intestinal stem cells (ISCs) and enhance their regenerative capacity in young animals. Data from my lab shows that ISCs from old mice have limited proliferation activity and form few if any organoids in vitro (a surrogate for a fully functional crypt) and that ISCs isolated from old mice on life-long DR show an improved ability to form organoids. While it is well accepted that life-long DR increases lifespan and has anti-aging effects an important aspect of DR that has been largely overlooked is that DR implemented only for a short time early in life can increase lifespan of rodents even when rodents are fed ad libitum the remainder of their life. In line with this, we recently found that ISCs from old mice fed DR for only a short-period resulted in a dramatic increase in ability of the ISCs to form organoids. This is the first evidence that short-term DR administrated late in life can rescue the loss in ISC function that occurs with age.

Download Full-text

Tissue Regeneration without Stem Cell Transplantation: Self-Healing Potential from Ancestral Chemistry and Physical Energies

Stem Cells International ◽

10.1155/2018/7412035 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Federica Facchin ◽

Eva Bianconi ◽

Silvia Canaider ◽

Valentina Basoli ◽

Pier Mario Biava ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Electromagnetic Fields ◽

Tissue Regeneration ◽

Adult Stem Cells ◽

Molecular Mechanisms ◽

The Body ◽

Self Healing ◽

Mechanical Vibrations

The human body constantly regenerates after damage due to the self-renewing and differentiating properties of its resident stem cells. To recover the damaged tissues and regenerate functional organs, scientific research in the field of regenerative medicine is firmly trying to understand the molecular mechanisms through which the regenerative potential of stem cells may be unfolded into a clinical application. The finding that some organisms are capable of regenerative processes and the study of conserved evolutionary patterns in tissue regeneration may lead to the identification of natural molecules of ancestral species capable to extend their regenerative potential to human tissues. Such a possibility has also been strongly suggested as a result of the use of physical energies, such as electromagnetic fields and mechanical vibrations in human adult stem cells. Results from scientific studies on stem cell modulation confirm the possibility to afford a chemical manipulation of stem cell fate in vitro and pave the way to the use of natural molecules, as well as electromagnetic fields and mechanical vibrations to target human stem cells in their niche inside the body, enhancing human natural ability for self-healing.

Download Full-text

A Comprehensive Conceptual and Computational Dynamics Framework for Autonomous Regeneration Systems

Artificial Life ◽

10.1162/artl_a_00343 ◽

2021 ◽

pp. 1-25

Author(s):

Tran Nguyen Minh-Thai ◽

Sandhya Samarasinghe ◽

Michael Levin

Keyword(s):

Stem Cells ◽

Stem Cell ◽

In Silico ◽

Large Scale ◽

Molecular Mechanisms ◽

The Body ◽

Algorithmic Complexity ◽

In Silico Studies ◽

Level 1 ◽

Tissue Cells

Abstract Many biological organisms regenerate structure and function after damage. Despite the long history of research on molecular mechanisms, many questions remain about algorithms by which cells can cooperate towards the same invariant morphogenetic outcomes. Therefore, conceptual frameworks are needed not only for motivating hypotheses for advancing the understanding of regeneration processes in living organisms, but also for regenerative medicine and synthetic biology. Inspired by planarian regeneration, this study offers a novel generic conceptual framework that hypothesizes mechanisms and algorithms by which cell collectives may internally represent an anatomical target morphology towards which they build after damage. Further, the framework contributes a novel nature-inspired computing method for self-repair in engineering and robotics. Our framework, based on past in vivo and in silico studies on planaria, hypothesizes efficient novel mechanisms and algorithms to achieve complete and accurate regeneration of a simple in silico flatwormlike organism from any damage, much like the body-wide immortality of planaria, with minimal information and algorithmic complexity. This framework that extends our previous circular tissue repair model integrates two levels of organization: tissue and organism. In Level 1, three individual in silico tissues (head, body, and tail—each with a large number of tissue cells and a single stem cell at the centre) repair themselves through efficient local communications. Here, the contribution extends our circular tissue model to other shapes and invests them with tissue-wide immortality through an information field holding the minimum body plan. In Level 2, individual tissues combine to form a simple organism. Specifically, the three stem cells form a network that coordinates organism-wide regeneration with the help of Level 1. Here we contribute novel concepts for collective decision-making by stem cells for stem cell regeneration and large-scale recovery. Both levels (tissue cells and stem cells) represent networks that perform simple neural computations and form a feedback control system. With simple and limited cellular computations, our framework minimises computation and algorithmic complexity to achieve complete recovery. We report results from computer simulations of the framework to demonstrate its robustness in recovering the organism after any injury. This comprehensive hypothetical framework that significantly extends the existing biological regeneration models offers a new way to conceptualise the information-processing aspects of regeneration, which may also help design living and non-living self-repairing agents.

Download Full-text