Rejuvenation therapies -
Which is why we encourage you to give us a call and speak with a trained professional. In order to decide if stem cell rejuvenation is right for you, it is important to schedule a personalized, one-on-one consultation to discuss your concerns and find out about our innovative solutions.
Contact us today! What is Stem Cell Rejuvenation Exactly? What Types of Stem Cell Rejuvenation Therapy is Offered by Stem Cell Doctors of Beverly Hills? Does Stem Cell Rejuvenation Require Surgery? Who is Stem Cell Rejuvenation Therapy For? Top Five Treatments for Erectile Dysfunction.
Try Stem Cell Therapy! Demystifying Stem Cells. Previous Post p The Non-Invasive FaceLift: How Stem Cell Treatment is Changing the Game. Next Post n The Future Of Medicine Is Regenerative Medicine.
Stem Cell Therapy. Share This. For example, EpSCs transplantation can regulate inflammation response, remodel the microenvironment of skin wounds, recapitulate tissue integrity and promote diabetic wound healing.
More importantly, transplanted MuSCs also accessed the satellite cell compartment, replenishing the endogenous stem cell pool and taking part in injury repair. It may be worthwhile to pursue methods for reactivating residual stem cells or combining such procedures with stem cell transplantation.
For instance, inhibition of the p38 MAPK signaling pathway in endogenous MuSCs can rescue muscle regeneration ability in ageing animals. The mechanism by which is in a manner of MDM2-dependent p53 degradation.
A recent clinical trial reported implantation of iPSC-derived dopaminergic progenitors into the putamen left hemisphere followed by the right hemisphere of a patient with PD indeed improved clinical symptoms of PD after surgery. Physiologically, extracellular signaling molecules are cues, such as EVs, neurotransmitters, growth factors, hormones, and cytokines, designed to transmit specific information to target somatic cells or adult stem cells.
EVs function as a cutting-edge tool for stem cell rejuvenation because of their ability to transfer genes safely and with systemic effects. For instance, ESC-EVs can directly facilitate pressure ulcer repair in ageing mice through the rejuvenation of tissue-resided senescent endothelial cells.
Injured tissue has a hostile environment, including inflammation, immune impairment, hypoxic stress, and poor blood supply, which degrades stem cell function, promotes cellular senescence, and results in a low survival rate of transplanted stem cells in vivo.
Therefore, it is essential for stem cells to remain viable and maintain their potency before inducing a strong repair response. The optimization of the culture environment, such as hypoxic pretreatment, may achieve preconditioning-induced protection for stem cells.
Particularly, ESCs require low oxygen levels to survive, which start at embryonic implantation and last throughout fetal development. Adult stem cells such as HSCs and BMSCs, similarly live in hypoxic conditions in vivo. For example, integrin receptors-mediated cell adhesion to the ECM is necessary for cell cycle progression, particularly during G2 to M transition and early mitosis.
Through the process of mechano-transduction, these mechanical cues are transformed into biochemical signals that affect immune cell functions such as cell activation, cytokine generation, metabolism, proliferation, and trafficking.
ECM molecules are continuously produced and secreted throughout life, in both physiologically healthy and pathological states, and they regulate a wide range of biological functions, including stem cell differentiation, angiogenesis, innervation, and wound healing.
Because ECM has a more favorable pro-remodeling host immune response and can offer a natural, instructional microenvironmental habitat for functional tissue remodeling, ECM-based biomaterials have been emerging and exhibit great variability.
Intercellular communication has double-edged—sword activities, contributing to tissue homeostasis maintenance but also detrimental in ageing and related diseases, and altered intercellular communication has been the hallmark of ageing.
The dominant role of inflammation in ageing-related intercellular communication raises the potential of anti-inflammatory agents in lifespan.
Aspirin is a common example because it can prolong mouse life and promote good ageing in humans. Correspondingly, GnRH treatment rejuvenates ageing-impaired neurogenesis and prevents ageing development. The use of DR, including time-restricted feeding TRF and calorie restriction CR , has many profound beneficial effects on ageing through the regulation of circadian clock.
It has been reported that the duration of two months for CR intervention in early life could enhance the amplitude of core clocks in liver. A functional circadian clock system is necessary for CR-mediated lifespan extension, as evidenced by the fact that CR fails to extend the lifespan of BMAL1 knockout mice.
Circadian clock-associated genes modulate the extrinsic and intrinsic mechanisms in lifespan modulation and organ ageing. The circadian clock in intervertebral discs IVDs is functional and temperature-entrainable, and ageing disrupts the circadian rhythm of IVDs in an inflammation-dependent manner and leads to IDD.
Numerous parts of human physiology are regulated by the circadian rhythm, opening up windows for interventions that can be made by only giving medications when their targets are at the proper expression level to rescue.
There is growing interest in developing small molecules that directly target the circadian system for medicinal benefits. KL specifically interacts with CRY, which prevents ubiquitin-dependent degradation of CRY, leading to extending circadian time. Immune system is interconnected with all the other systems in the body, and this systemic nature provides the potential opportunity that targeted modifications to a small group of cells e.
As the origin of blood cell lineages, HSCs are multipotent precursors population that can reconstitute the hematopoietic system and sustain immune homeostasis.
Ageing HSCs have less self-renewal activity, fewer cell divisions, decreased homing efficiency and myeloid lineage-biased differentiation as well as reduced output of lymphoid progenitors.
HSCs ageing is accompanied by alterations at the gene level, and genetic modulators by ablation of genes driving ageing or overexpression of rejuvenative genes might be strategies to prevent HSCs dysfunction, such as the deletion of the imprinted gene Grb10 or forced expression of Satb1.
For example, supplementing elderly mice with a sympathomimetic that specifically targets the adrenoreceptor β3 β3-AR agonist, BRL greatly improved the in vivo function of aged HSCs. Immune lineage-mediated cellular rejuvenation mainly focuses on the restoration of T lymphocytes exhaustion caused by organismal ageing, due to its high susceptibility to ageing-associated changes to the immune system.
Preclinical results have shown that proT cells could effectively engraft involuted ageing thymuses, achieve rapid long-term thymic reconstitution and accelerate T cell recovery.
Therefore, ProT cells avoid the clinical concerns brought on by graft-versus-host disease GVHD , and it provides an alternative cell-based strategy to rejuvenate T-cell immunity clinically. As the key site of T lymphopoiesis, the thymus orchestrates adaptive immune responses, and ageing-associated thymic atrophy or involution contributes to adaptive immune system deviations.
Cellular reprogramming provides an alternative avenue for thymus function restoration and immune rejuvenation. Chemical activation of thymus organogenesis program can direct human ESCs to differentiate into thymic precursor lineage, further promoting functional regeneration of human thymus in vivo.
T cells produced in TEPs-recipient mice have functional properties capable of in vitro expansion and in vivo immune responses, and they were detected 10 weeks post-transplantation in the peripheral blood.
However, the regenerative efficiency of hESCs-TEPs generated by these protocols is low and there is a progressive decrease in the quantity of T cells produced, which was not sustained over 22 weeks. In , heterochronic parabiosis was initially demonstrated to reverse the age-dependent loss in stem cell function by restoring the proliferation and regeneration capacity of aged satellite cells and hepatic progenitor cells in naturally aged mice.
For example, in the central nervous system, heterochronic parabiosis showed young mice exposed to an old systemic environment or plasma from old mice exhibited diminished synaptic plasticity, and worse contextual fear conditioning and spatial learning and memory, while systemic infusion of young blood plasma reversed that process.
Young mice with elevated peripheral CCL11 chemokine levels in vivo suffered adult neurogenesis loss as well as learning and memory impairments. Aged mice and young heterochronic parabionts have high levels of B2M in their blood and hippocampus, and the ablation of endogenous B2M can alleviate age-related cognitive loss and improve neurogenesis.
Nevertheless, the key obstacles of parabiotic experimentation facing include the difficulty to control experimental procedures, the influences of shared organs, uncontrollable exercise, and an ambiguous blood-sharing onset.
The persuasive evidence that blood factors affect organismal ageing has been provided by heterochronic blood exchange HBE , which has shown that circulating factors not only restore youthful traits to aged tissues but also cause systemic senescence in the young organism.
Thus, defining the blood mediators of the rejuvenating effects is of great importance to revitalize aged organs and tissues.
A nontargeted, quantitative metabolomics analysis in the blood of 15 young and 15 elderly individuals reported that 14 metabolites showed significantly remarkable age-related alternations.
A longitudinal examination of the impacts of ageing on the blood plasma metabolome also identified pathways enriched for age-related metabolites embodied tryptophan, nucleotide, and xenobiotic metabolism. It was reported that aged mice exposed to young blood showed muscle regeneration, in which serum EVs containing α-Klotho play a key role, and administration of Klotho-enriched EVs into ageing mice could promote muscle regeneration.
Deeper insights into the role of cellular senescence in disease pathogenesis highlight the significance of cellular rejuvenation in treating human disorders, and also provides cues for rejuvenation therapies Table 1. In addition, a variety of pharmacological treatments with the elimination of SCs or reversal of tissue and organ ageing have been developed for cellular rejuvenation Table 2.
The discussion that follows will thus concentrate on the advances in rejuvenation strategies for alleviating human diseases, and the details of clinical trials in this study were shown in Table 3. Diabetes, as a metabolic disorder featured by increased blood glucose, result from defective insulin function, impaired insulin secretion, or both, which has increased mortality in recent years.
The known etiological basis of diabetes can provide hints for rejuvenation strategy for treatment. SCs contribute to the pathophysiologies of diabetes via their direct impact on pancreatic β-cell function, involvement in adipose tissue malfunction, and SASP-associated tissue inflammation.
Currently, systemic interventions for diabetes treatment seem to be more likely from bench to bedside, which have been explored in the diabetes population. Obesity is characterized as an abnormal or excessive accumulation of fat that presents a health risk. The signal transduction pathways mediating obesity pathophysiology have been widely explored.
Currently, a variety of anti-obesity drugs targeting obesity-related regulation pathways have been explored and even under clinical trials, such as melanocortin-4 receptor MC4R agonists, neuropeptide y receptor y5 NPY5R antagonist and glucagon-like peptide 1 receptor GLP-1R agonist, etc.
The mechanisms of these interventions against obesity are mainly related to the control of calory intake, glucose balance and thermogenesis.
Cellular rejuvenation for tissue regeneration is devoted to the enhancement of tissue-specific cell function and the regulation microenvironment. These encourage the development of exogenous activation of tissue-residing stem cells to recapitulate damaged tissue, such as biomaterials-based delivery system featured by controlled and sustainable drugs or other biologically active substances release, in osteochondral regeneration, wound healing, and spinal cord repair, and so on.
For example, SCs-matrix interaction is responsible for the difficulty in healing in chronic wounds, because the SASP and ROS production from SCs results in increased matrix proteolysis and inflammation, dysfunction in stem cell, impaired vascular endothelial cells and exacerbated inflammatory microenvironment, and in turn, the microenvironment disturbance further accelerates cellular senescence.
These approaches contain clearance of SCs with senolytics, exogenous stem cell transplantation for replenishing the stem cell pool, EVs and their engineered derivatives for alleviating cellular senescence, and wound inflammatory and chemical compounds for rejuvenating SCs, etc.
However, targeting tissue cells and microenvironment fails to achieve the functional regeneration of the large tissue defect or other severe and irreversible tissue damage, such as deep second-degree skin burns, diabetic ulcers, and massive liver defects. Recent advancements in somatic cell reprogramming technology have brought to light the possibility of functional repair of damaged tissue.
Impressively, the regeneration of sweat gland cells by epidermal cell, fibroblasts, and MSCs reprogramming not only promotes wound healing in deep second-degree burned skin, but also confers the sweat function, which achieves the functional repair of damaged skin.
Currently, to overcome this obstacle, in situ regeneration based on in vivo reprogramming has developed rapidly, which is applicated to the regeneration of pancreatic β cells, induced cardiomyocyte-like cells, expandable neural stem cells, and sensory hair cells.
Clearance of SCs has become lucrative methodology for osteoporosis treatment. Age-related osteoporosis has been demonstrated to be improved by genetic elimination of p16, and a combination of D and Q also performed well in repairing bone microstructure as seen in radiation-related osteoporosis.
Senomorphics that prevent the production of pro-inflammatory proteins, like the JAK inhibitor ruxolitinib, significantly reduce age-related osteoporosis by possibly suppressing certain factors like IL6, IL8, and PAI1.
OA is a degenerative disease of the cartilage that develops with ageing and shares a pathogenesis with the SASP and senescence of joint tissue cells.
SASP has been linked to cartilage deterioration, and age-related mitochondrial dysfunction and accompanying oxidative stress may cause senescence in joint tissue cells.
Navitoclax and UBX are potential senolytic agents that work to alleviate OA, and the trial of UBX in OA has been completed clinically NCT Fisetin is a more selective senolytic candidate with lower hematological toxicity, which can activate SIRT1 to block the inflammatory response in OA chondrocytes, and Fisetin is now undergoing a clinical trial as a treatment for OA NCT Senomorphic agents targeting MMPs can reduce OA symptom, increase type II collagen and inhibit chondrocyte degeneration in WT mice.
The accumulating evidences have indicated the contributions of cellular senescence to AD pathophysiology, by which telomerase deficiency and telomere shortening, accumulation of β-amyloid Aβ , tauopathy, and oxidative stress get involved.
The first-generation senolytic ABT is able to clear senescent astrocytes and microglia, modulate tau aggregation and inhibit tau-associated cognitive decline. Stem cell-based therapies against neurodegenerative diseases hold promise. MSCs can enhance spatial learning and prevent memory impairment in AD via various mechanisms including reducing Aβ plaques and tau hyperphosphorylation, reversing microglial inflammation, and promoting anti-inflammatory response.
The transplantation of NSCs with paracrine effect can decrease tau and Aβ levels, alleviate neuroinflammation, improve neurogenesis and enhance cognitive function via releasing neuroprotective or immunomodulatory factors.
The incidence and prevalence of a wide range of cardiovascular diseases CVD increase as a function of age. Molecular pathways involved in cellular senescence, oxidative stress, insulin signaling, autophagy, and inflammation may link the cardiovascular homeostasis deterioration.
Chronic lung disease CLD refers to a spectrum of persistent lung conditions that impair quality of life and are typically resistant to treatment. The conventional therapy regime for CLD treatment with nasal medications, immune-suppressive drugs, and surgery in severe cases only supports the decrease of disease progression rate.
Cellular rejuvenation strategies based on stem cell therapy have ushered an alternative in the treatment of CLD. People with CLD may benefit from stem cells in the following ways: 1 lowering airway inflammation and preventing additional harm; 2 creating new, healthy lung tissue to replace any damaged tissue in the lungs; 3 promoting the development of new capillaries with tiny blood channels to enhance lung function.
Based on the differentiation potential of stem cell therapy, ex vivo lung bioengineering also offers exciting new therapeutic approaches for CLD, which contains physical stimuli such as air ventilation and blood perfusion and stem cell to create a functional lung organ.
However, the most important issues to be resolved are how to provide the lung with the ideal conditions of ventilation, perfusion, and oxygenation during the biofabrication process, as well as the best cell types, media, and growth factors being likely various for the airway and vascular compartments.
Macular degeneration, often known as age-related macular degeneration AMD , is a serious eye condition underlined by photoreceptor loss and choriocapillaris and retinal pigment epithelium RPE degenerating CC.
The accumulating evidence shows that AMD is mainly attributable to oxidative stress, cellular senescence, and inflammation. Glaucoma and age-related cataract ARC are also chronic, progressive eye diseases, and regeneration and re-functionalization of damaged trabecular meshwork TM or lens with stem cells have been regarded as a therapeutic alternative for these two conditions.
A number of stem cells, including trabecular meshwork stem cells TMSCs , ESCs, iPSCs, and MSCs, have demonstrated efficacy in maintaining intraocular pressure IOP equilibrium and restoring TM cellularity.
Chronic kidney disease CKD is charactered by persistent kidney function decline, and its progressive nature often results in end-stage renal disease ESRD. The growing evidences revealed that cellular senescence, stress-induced premature ageing, SASP, oxidative stress, and inflammation-mediated CKD development.
Various drugs targeting SASP, like glucocorticoids, resveratrol and other protease inhibitors have been reported to attenuate CKD, and most of these mainly inhibit NF-κB signals and reduce ROS. Both bone marrow MSC and adipose-derived MSC have been shown to have significant renoprotective effects in CKD, including a decrease in fibrosis and glomerulosclerosis as well as an intrarenal inflammatory infiltrate.
Trials employing MSCs to treat CKD may encounter a number of difficulties, including choosing the best administration method, assuring flourishing, tracking injected cells, immunological rejection, inadequate homing and engraftment, and low immune acceptance. The term fibrosis describes the deposition of fibrous connective tissue as a reparative response to injury or damage, particularly during chronic inflammatory disorders, and Fibrosis leads to tissue architecture disruption, organ malfunction, and eventually organ failure.
Based on that known molecular mechanism, numerous cellular rejuvenation strategies to treat fibrosis have been developed. A key contributor to fibrosis is metabolic reprogramming, which includes increased glycolysis, upregulated glutaminolysis, and accelerated fatty acid oxidation. Miscommunications of macrophage-fibroblast interactions also result in pathological healing and fibrosis, and the restoration of macrophage and fibroblast crosstalk through IGF1 and platelet-derived growth factor C PDGFC can reduce tissue dysfunction.
Pharmacologically blocking TGF-β1 signaling e. Strong preclinical studies have identified pro-inflammatory cytokines e. During the process of fibrosis, myofibroblasts exhibit remarkable inter-lineage plasticity, which provides opportunities for cellular reprogramming in fibrosis treatment.
During cutaneous wound healing, neogenic hair follicles-derived BMP signaling can reprogram myofibroblasts into adipocytes. Finally, in vivo reprogramming induces myofibroblasts into other functional desired cells, which can not only attenuate fibrosis and also realize in situ tissue repair.
The strong evidences link chronic inflammation to autoimmune disease pathogenesis, including rheumatoid arthritis RA , systemic lupus erythematosus SLE , multiple sclerosis MS , inflammatory bowel disease IBD , psoriatic arthritis PsA , primary Sjögren syndrome PSS and psoriasis, etc.
Inflammatory cytokines e. Targeting TNF-ɑ therapy including monoclonal antibodies e. Immunosuppression of T cells activation by CTLA4-IgG1 Fc Abatacept and anti-CD40 mAb Iscalimab in autoimmune diseases also has been studied.
Now, Abatacept NCT and NCT and Iscalimab NCT have been tested in phase 2 trials for PSS treatment. B cell depletion therapies show great potential for the treatment of autoimmune diseases, and likewise, a large number of monoclonal antibodies targeting B cells function also has been developed, such as anti-CD20 mAb Rituximab, Ocrelizumab, Ofatumumab, and Ublituximab , anti-CD19 mAb Inebilizumab , anti-BAFF mAb Belimumab and anti-BAFF-R mAb Ianalumab , in which Ublituximab for MS NCT, NCT, NCT and Ianalumab for SLE NCT are under the phase 2 trials.
Treatment and clinical results for people with autoimmune diseases have been changed by improvements in tailored immunotherapy, but immunosuppression based on decreasing inflammation may lead to serious side effects, such as increasing the risk of infection.
Other ageing and age-related diseases are also matters of great concern, including skin ageing, skeletal muscle ageing, reproductive system ageing, and ageing-related hearing loss.
Skin ageing is currently a very concerning field, and the reversal or delay of skin ageing has a great market prospect. The process of skin ageing is multifactorial and is influenced by both intrinsic such as time, genetics, and hormones and extrinsic such as UV exposure, and pollution variables.
Senescent skin cells, SASP, oxidative stress, inflammation, and autophagy, all mediate skin ageing pathophysiology. Fu et al. reported the phenomenon that epidermal cells can de-differentiation into stem cells in vivo during wound healing, and this discovery was the first to reveal that adult cells can become adult stem cells, which suggested that the high plasticity of epidermal cells and cellular fate was not one-street.
demonstrated that dedifferentiation-derived cells cultivated in vitro shared phenotypic and functional traits with EpSCs. Currently, topical cosmetics like sunscreen, retinoids, or resveratrol are the foundation of current strategies for combating skin ageing. Anti-ageing drugs such as senolytics or senomorphics may be useful for skin rejuvenation, because such drugs have anti-inflammatory and melanogenic properties that help protect the skin, prevent carcinogenesis, delay ageing, and reduce age-related diseases.
The administration of natural products, especially polyphenols with known antioxidative properties, show the ability to enhance or remove the undesirable signs of ageing skin. Evidence-based knowledge suggests that the topical or oral use of various polyphenol-rich plants can prevent or reduce, besides others, undesirable conditions of skin ageing.
The developed strategies include stem cells and related EVs, pharmacological activation of autophagy, maintenance of circadian rhythmicity on skin-resided stem cell , and regulation of metabolism homeostasis to restore mitochondrial integrity and metabolic output.
The role of COL17A1 in EpSC competition to orchestrate skin homeostasis and ageing and COL17A1 overexpression against skin ageing also were revealed. Y and apocynin have been identified as COL17A1-inducing drugs, which show the capacity to facilitate skin regeneration and reduce skin ageing.
For example, using tetrahedral framework DNA tFNA to design a novel bio-switchable miRNA inhibitor delivery system BiRDS , which can fuse miR inhibitors within the framework and maximize the loading ability.
MiR inhibitors-loaded BiRDS have excellent skin penetration and high RNA delivery efficiency, significantly combating skin ageing. While most studies have focused on the function of senescence in non-cancer cells, it is clear that cancer cells may also establish a senescence response, which makes it possible to exploit senescence to treat cancer.
Induction of senescence in tumors includes chemotherapy, radiotherapy, cell cycle inhibition, and telomerase inhibition. However, persistently therapy-induced senescence TIS may create a pro-inflammatory microenvironment. For example, navitoclax has shown desired results when combined with various TIS, including ionizing radiation, rituximab CD20 antibody , doxorubicin, paclitaxel, docetaxel, or gemcitabine.
For sequential treatment regimen in cancer, the issue that need to be solved is identifying pro-senescence drugs with high efficacy and selectivity in inducing cancer cell senescence.
It is well recognized that cancer cells can develop a malignant transition from benign cells, but the question that whether it is possible to genetically and epigenetically transform malignant cancer cells to benignity is interesting.
The discovery of somatic cell reprogramming encourages the idea that cancer cells, featured by genetic and epigenetic plasticity, can rescue benign cell functions by cellular reprogramming theoretically. Cell reprogramming techniques that trigger the switch from malignancy to benignity include transcription factors, chemical cocktails, microRNAs, and exosomes Fig.
The conversion of cancer cells to iPSCs with benign phenotypes has been frequently studied. With the induction of pluripotency-associated transcription factors, melanoma cells, hepatoma cells, and colorectal cancer cells, lung adenocarcinoma and gastrointestinal cancer cell can be reprogrammed into iPSCs, and these cancer cells-derived iPSCs maintain benignity without the formation of a visible tumor in vivo.
More importantly, these differentiated cancer cells are less aggressive and lack the ability to form tumors than their parental cancer cells.
Lineage-specific factors manipulation also has shown proven capabilities to directly convert cancer cells to desired functional cells without the acquisition of pluripotency. The urgent need for developing optional methods is driven by safety and effectiveness concerns brought on by genetic manipulations.
The chemical reprogramming technology based on small molecules has some particular advantages, such as affordability, ease of use, versatility that is easily programmable, permeability, and reversibility. Lin et al. reported using microRNAs could convert skin cancer cells into iPSCs with decreased tumorigenicity and genomic demethylation.
ESCs-derived exosomes also deliver ESC-related reprogramming factors to convert malignant cells to benignity ones. The mechanisms for cellular reprogramming in cancer. Cancer cell reprogramming treatment aims to convert the malignancy to benignity or provide a therapeutic target to inhibit the formation of CSCs.
Yamanaka factors-mediated iPSCs technology has been recognized as a common method for the conversion of cancer cells to benign pluripotent cells, and cancer cells-derived iPSCs can re-differentiate into functional cells with less malignancy and free of tumorigenic potential.
Cancer cells also can be directly reprogrammed into benign cells via various reprogramming strategies, such as lineage-specific factors, small molecules, microRNAs, and exosomes. Responsive cellular reprogramming based on EMT contributes to CSCs formation, which mediates the initial, progression, metastasis, and post-treatment recurrence.
The role of cellular reprogramming in the formation of CSCs suggests that anti-cellular reprogramming strategies may be considered as a therapeutic alternative in cancer treatment. EMT Epithelial—mesenchymal transition.
The increasing evidence suggests that cellular reprogramming also contributes to cancer initiation, development, and recurrence Fig. Specific transcription factors silence- or epigenetic gene mutation-mediated cellular reprogramming initiate cancer initiation.
For example, the depletion of PTEN in NSCs could activate Paired Box 7 PAX7 and induce the generation of glioblastoma stem cell-like cells, which can lead to intracranial tumors in vivo.
In non-small cell lung cancer, Lkb1 deficiency induced the trans-differentiation of adenocarcinoma cells into squamous cell carcinoma. Conventional anti-cancer therapeutics, including chemotherapy and radiotherapy, enable cancer cells to become CSCs.
For example, in non-small cell lung cancer, cisplatin-based chemotherapy renders p53 inactive and induces Tribbles Pseudokinase 1 expression, which leads to stemness activation in cancer cells.
Anti-angiogenesis therapy also has a great deal of potential in treating cancer, and antiangiogenic agents drive CSCs reprogramming by generating tumor hypoxia microenvironment. In melanomas, T cell-driven inflammatory stimuli lead to melanomas cells with the transition of the differentiated and dedifferentiated state and confer the ACT resistance.
Synergistic therapy of conventional therapeutics and anti-cellular reprogramming may represent a promising strategy in cancer treatment.
In the future, identifying molecular mechanisms involved in CSCs reprogramming is of great significance to anti-cellular reprogramming therapy. The discovery of epidermal cell de-differentiation into stem cells and somatic cell reprogramming into iPSCs revealed that cell fate is not a one-way street.
Terminally differentiated cells can reset their genetic and epigenetic properties and acquire the undifferentiated phenotype, and likewise, SCs can also get rid of senescence-related signatures and restore the youthful state.
Emerged evidence has indicated the important contribution of cellular senescence in ageing and ageing-related diseases, which encourages the hypothesis that the reversal of ageing may be possible, and targeting cellular senescence may pave the way for that.
The development of various cellular rejuvenation strategies provides compelling evidences that the ageing process is not irreversible. Particularly, the effectiveness of stem cell therapy and DR has been tested in the real world, yielding to desired results.
Hopefully, there is a great possibility of translation of these rejuvenation strategies to address human ageing, age-associated diseases, and cancers. Therefore, it is reasonable to expect that clinical rejuvenation approaches to treat ageing-related diseases and even to reverse ageing will be boomed within the next two or three decades.
Throughout human history, the quest to extend lifespan or restore youthful state has been relentless. With the enormous progress in medical technology, including a deeper understanding of cell senescence and age-associated pathophysiology, it has become plausible to extend the human lifespan while preserving health.
It is extremely essential to gain insight into the basic principles regulating cellular rejuvenation. Although many aged phenotypic and functional characteristics are studied, the formation, maintenance, and functional contribution to the disease process of aged cells still need further exploration.
The study of cellular rejuvenation targeting ageing-related mechanisms is promising to develop potential therapeutic interventions for postponing and reversing ageing, and treating ageing-related diseases. For decades, one of the dominant theories in ageing research has been that ageing results from the accumulation of DNA changes, mainly genetic mutations, which prevent more and more genes from functioning properly over time.
These malfunctions, in turn, can cause cells to lose their properties, leading to the breakdown of tissues and organs and ultimately to ageing and diseases. However, the emerging evidences claim that epigenetic information loss over time is the major cause of mammalian ageing, and epigenetic regulation can restore youthful gene expression patterns.
Current advances have provided a comprehensive and detailed multi-level epigenetic panorama of ageing, elucidated some common and unique characteristics of physiological ageing and ageing-related diseases, identified novel biomarkers of ageing, and revealed new mechanisms of epigenetic remodeling in cell and organ ageing.
It is expected that future research on ageing epigenetic inheritance will further expand the relationship between chromatin three-dimensional structure and function. Especially, with the development of epigenetic editing technology, scientists can make specific perturbations to the epigenome, to distinguish the causal relationship between the three-dimensional structure of chromatin and cell function.
Epigenetic changes caused by ageing in more diverse cell types and pathophysiological states should also be extensively explored to discover conditional regulation mechanisms of ageing. For epigenetic rejuvenation, developing safe and stable strategies that modulate the epigenetic landscape of aged cells to a primitive state are important for cells to exert rejuvenating effects without cancer risk.
Furthermore, systematic comparisons of epigenetic dynamics during ageing and partial reprogramming will contribute to identifying key checkpoints for reversing the ageing process and inform the design of potential intervention strategies for ageing-related diseases.
Pathological accumulation of SCs is also associated with ageing and a range of diseases, and SCs may be potential pharmacological targets for delaying the ageing process. In respect of targeting SCs, there are still many potential markers, like chromatin dynamics and transcriptional signaling, and pharmacological interventions deserving exploitation, to effectively regulate the secretory phenotype of SCs.
SC elimination and SASP inhibition have shown some efficacy in clinical studies of treating functional degeneration and chronic diseases in ageing.
Notably, SC populations are heterogeneous in terms of composition, function, and tissue distribution, even among species, which is also a problem in the transition from laboratory to clinic. Therefore, identifying the cell or organ-specific markers of SCs is of great guiding significance for future clinical treatment.
Targeting the cell microenvironment and systemic signals makes sense for tissue-specific cell and organism rejuvenation. Stem cells play a crucial role in maintaining tissue homeostasis, and cell microenvironments also regulate stem cell behavior, which together form a regenerative unit.
External signals from the ageing microenvironment appear to dominate the intrinsic function of young stem cells. In contrast, signals from the young microenvironment may have a limited effect on the regeneration of aged stem cells.
It would be interesting to identify the genes or pathways that make aged stem cells insensitive to external signals in young microenvironment.
Although many clinical trials registered for stem cell treatments, an effective and safe stem cell therapy to slow or reverse tissue ageing has not yet been identified.
Several obstacles still need to be overcome, including proper differentiation and integration of cells in tissues, maintenance of the youth of stem cells and their progeny in ageing tissues, and prevention of tumorigenesis. It will be important to determine the specific mechanisms, which have the potential to provide better treatment pathways-using stem cell transplantation or utilizing endogenous stem cell banks.
Recent advances in single-cell transcriptomics and pedigree tracing techniques provide a systematic understanding of stem cell ageing mechanisms. Developing and utilizing new techniques to track and manipulate stem cells will still be a key field. The systematic identification of gene networks, involved in functional changes, age-dependent changes in RNA and protein and metabolite molecules, and cellular interactions, will contribute to further studies on stem cells in tissue repair and ageing-related diseases.
In addition, rejuvenating strong circadian rhythms can optimize organismal physiology and avoid the risk of disease to prolong health. Clinically, circadian rhythms including a series of cyclical life activities, such as diet, sleep and exercise, vary from person to person.
It is of great clinical value to develop methods to predict individual circadian rhythms. Machine learning and artificial intelligence methods may help to identify a series of biomarkers to predict circadian rhythms, which has great application prospects for determining the optimal biological clock pattern for each individual.
Despite the great progress in cellular rejuvenation, the potential limitations have led to cellular rejuvenation rarely being tested in human studies. Cellular rejuvenation for reversing ageing and age-related diseases as well as cancers has been extensively studied.
While cellular rejuvenation holds great promise, key questions remain to be addressed. The toxicity might be induced by drug combinations, then reducing the effectiveness of the cocktail and causing side effects in normal cells. Besides, completely senescence-specific markers are still absent. Despite the advances in many clinical trials of stem cell therapy, optimizing in vitro culture environment, improving the delivery system of stem cells, and reducing immune rejection are still the major challenges to obtain high-quality stem cells and enhance that therapeutic effect.
Collectively, cellular rejuvenation holds great promise for preventing and treating ageing-related diseases from different dimensions. A healthy and rejuvenated state of the organism can maintain stable characteristics and biological functions without excessive ageing-related degeneration or deterioration.
Of note, system therapies such as DR and exercise are available rejuvenation strategies mostly closed to bedside, whose mechanism at the cellular level and molecular level has been expounded. Exercise greatly activates the immune system, facilitates DNA repair processes, maintains metabolism homeostasis, and is capable of lowering the risk of diabetes, obesity, cancer, osteoporosis, AD, and depression as well as prolonging the lifespan.
Luo, J. Ageing, age-related diseases and oxidative stress: what to do next? Ageing Res. Article CAS PubMed Google Scholar. Kubben, N. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.
Cell Biol. Article CAS PubMed PubMed Central Google Scholar. Dai, X. Decoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations. Vaiserman, A. Anti-ageing gene therapy: Not so far away? Article PubMed Google Scholar. Gage, F. Aging and rejuvenation: insights from rusty gage, leonard guarente, and amy wagers.
Trends Mol. Soria-Valles, C. iPSCs: on the road to reprogramming aging. Lopez-Otin, C. The hallmarks of aging. Cell , — Zhang, B. Emerging rejuvenation strategies—reducing the biological age. Aging Cell 21 , e Sender, R. The distribution of cellular turnover in the human body. Henikoff, S.
Histone variants and epigenetics. Cold Spring Harb. Article PubMed PubMed Central Google Scholar. Saul, D. Epigenetics of aging and aging-associated diseases. Wang, Y. Histone modifications in aging: the underlying mechanisms and implications.
Stem Cell Res. Greer, E. Histone methylation: a dynamic mark in health, disease and inheritance. Braga, D. Epigenetic changes during ageing and their underlying mechanisms. Biogerontology 21 , — Ciccarone, F. DNA methylation dynamics in aging: how far are we from understanding the mechanisms?
Ageing Dev. Lillycrop, K. DNA methylation, ageing and the influence of early life nutrition. Gabbianelli, R.
Epigenetics in ageing and development. Borghesan, M. et al. DNA hypomethylation and histone variant macroH2A1 synergistically attenuate chemotherapy-induced senescence to promote hepatocellular carcinoma progression.
Cancer Res. Petkovich, D. Using DNA methylation profiling to evaluate biological age and longevity interventions. Cell Metab.
e Unnikrishnan, A. The role of DNA methylation in epigenetics of aging. Article CAS Google Scholar. Zhang, Y. Epigenetics and obesity cardiomyopathy: from pathophysiology to prevention and management. Watanabe, R. Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing.
B Biol. Swer, P. ATP-dependent chromatin remodelers in ageing and age-related disorders. Biogerontology 22 , 1—17 Tessarz, P. Histone core modifications regulating nucleosome structure and dynamics. Kane, A. Epigenetic changes during aging and their reprogramming potential.
Biochem Mol. Ilina, A. Menoni, H. Chromatin associated mechanisms in base excision repair - nucleosome remodeling and DNA transcription, two key players.
Free Radic. Kamileri, I. Nucleotide excision repair: new tricks with old bricks. Trends Genet. Martinez Corrales, G. Evolutionary conservation of transcription factors affecting longevity.
Loaiza, N. Cellular senescence and tumor promotion: Is aging the key? Acta , — CAS PubMed Google Scholar. Cheng, Y. Preserving transcriptional stress responses as an anti-aging strategy.
Aging Cell 20 , e Martins, R. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15 , — Li, G. Epigenetic regulation in intervertebral disc degeneration.
Harries, L. Dysregulated RNA processing and metabolism: a new hallmark of ageing and provocation for cellular senescence. FEBS J. Epigenetics and aging. Maturitas 74 , — Lozano-Vidal, N. Long noncoding RNA in cardiac aging and disease.
Jusic, A. Noncoding RNAs in age-related cardiovascular diseases. Miyata, K. Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer. Natl Acad. USA , e Bandaria, J. Shelterin protects chromosome ends by compacting telomeric chromatin.
Campisi, J. Does damage to DNA and other macromolecules play a role in aging? If so, how? A Biol. Gorgoulis, V. Cellular senescence: defining a path forward. Shay, J. Telomeres and aging. Rossi, M. Noncoding RNAs controlling telomere homeostasis in senescence and aging. Fernando, R. Impaired proteostasis during skeletal muscle aging.
Korovila, I. Proteostasis, oxidative stress and aging. Redox Biol. Klaips, C. Pathways of cellular proteostasis in aging and disease.
Stein, K. Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis. Nature , — Das, U. Biomolecules 11 , Roitenberg, N. Lipid assemblies at the crossroads of aging, proteostasis, and neurodegeneration. Trends Cell Biol. Skowronska-Krawczyk, D.
Aging membranes: unexplored functions for lipids in the lifespan of the central nervous system. Almeida, I. Lipids: biomarkers of healthy aging.
Biogerontology 22 , — Zhu, X. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct. Target Ther.
Azzu, V. Energy metabolism and ageing in the mouse: a mini-review. Gerontology 63 , — Rajawat, Y. Aging: central role for autophagy and the lysosomal degradative system. Terman, A. Mitochondrial damage and intralysosomal degradation in cellular aging. Sreedhar, A. Mitochondria in skin health, aging, and disease.
Cell Death Dis. Breitenbach, M. Mitochondria in ageing: there is metabolism beyond the ROS. FEMS Yeast Res 14 , — Suganuma, T. Chromatin and Metabolism. Sharma, R. The aging metabolome-biomarkers to hub metabolites.
Proteomics 20 , e Amjad, S. Sahin, E. Telomere dysfunction induces metabolic and mitochondrial compromise. Lee, D. The role of dietary carbohydrates in organismal aging.
Cell Mol. Life Sci.
Thank you therapiess visiting tjerapies. You are using a browser Antioxidant properties of spinach and leafy greens with limited support for CSS. Ginseng benefits obtain the Rejuvenatiion experience, we recommend thwrapies use a Rejuvenatin up to Preventing and repairing signs of aging browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition to deteriorated disorders. Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques, such as cellular reprogramming and epigenetic regulation. Rejuvenation Rejuvenatiob a medical Antioxidant properties of spinach and leafy greens thwrapies on the practical reversal of the aging process. Rejuvenation is distinct from life extension. Life extension strategies often Rejuvenatino the Artichoke main courses of theapies Rejuvenation therapies try to oppose those causes in order to slow aging. Rejuvenation is the reversal of aging and thus requires a different strategy, namely repair of the damage that is associated with aging or replacement of damaged tissue with new tissue. Rejuvenation can be a means of life extension, but most life extension strategies do not involve rejuvenation.
die sehr ausgezeichnete Idee und ist termingemäß
Genau, Sie sind recht