Molecular mechanisms of aging and anti-aging strategies

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Abstract Aging is a complex and multifaceted process involving variety of interrelated molecular mechanisms cellular systems. Phenotypically, the biological aging accompanied by gradual loss function systemic deterioration multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, protein balance, deregulated nutrient sensing, altered intercellular communication, dysbiosis. These age-related changes may be alleviated intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, targeted longevity genes. In this review, we summarise key historical progress exploration important causes anti-aging strategies recent decades, which provides basis for further understanding reversibility phenotypes, application prospect synthetic biotechnology therapy also prospected.

Language: Английский

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Is Senescence-Associated β-Galactosidase a Reliable in vivo Marker of Cellular Senescence During Embryonic Development?

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Jan. 28, 2021

During vertebrate embryonic development, cellular senescence occurs at multiple locations. To date, it has been accepted that when there induction of in an tissue, β-galactosidase activity is detectable a pH as high 6.0, and this extensively used marker vivo both whole-mount cryosections. Such senescence-associated (SA-β-GAL) labeling appears enhanced degenerating regions the embryo are also affected by programmed cell death. In sense, strong SA-β-GAL signal which overlaps with pattern death interdigital tissue developing limbs, indeed, many labeled cells detected go on to subsequently undergo apoptosis. However, reported β-GAL 6.0 healthy neurons, some retinal neurons strongly histochemical technique they begin differentiate during early development. These post-mitotic express other markers such p21. Therefore, reliability studying prolonged irreversible cell-cycle arrest questionable because expressed cells. The identification new biomarkers would, combination established markers, increase specificity efficiency detecting mature tissues.

Language: Английский

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The jam session between muscle stem cells and the extracellular matrix in the tissue microenvironment

npj Regenerative Medicine, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 17, 2022

Skeletal muscle requires a highly orchestrated coordination between multiple cell types and their microenvironment to exert its function maintain homeostasis regenerative capacity. Over the past decades, significant advances, including lineage tracing single-cell RNA sequencing, have contributed identifying resident populations participating in maintenance repair. Among these populations, stem cells (MuSC), also known as satellite cells, response stress or injury, are able proliferate, fuse, form new myofibers repair damaged tissue. These reside adjacent myofiber surrounded by specific complex microenvironment, niche. Major components of niche extracellular matrix (ECM) proteins, instruct MuSC behavior. However, during aging muscle-associated diseases, progressively loses ability, part due dysregulation ECM components. This review provides an overview composition importance microenvironment. We discuss relevant proteins how mutations impact young aged tissue contribute diseases. Recent discoveries improved our knowledge about skeletal muscle, which has helped mimic architecture capacity MuSC. Further understanding extrinsic signals from controlling innovative technologies still required develop therapies improve

Language: Английский

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Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Cellular senescence is characterized by the permanent arrest of cell proliferation and a response to endogenous exogenous stress. The continuous accumulation senescent cells (SnCs) in body leads development aging age-related diseases (such as neurodegenerative diseases, cancer, metabolic cardiovascular osteoarthritis). In face growing challenge several compounds have received widespread attention for their potential target SnCs. As result, senolytics (compounds that selectively eliminate SnCs) senomorphics alter intercellular communication modulate behavior become hot research topics field anti-aging. addition, strategies such combination therapies immune-based approaches also made significant progress anti-aging therapy. this article, we discuss latest on targeting SnCs gain deeper understanding mechanism action impact different with aim providing more effective references therapeutic ideas clinical treatment ever-grave challenges diseases.

Language: Английский

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Inflammation and Oxidative Stress in Frailty and Metabolic Syndromes—Two Sides of the Same Coin

Metabolites, Journal Year: 2023, Volume and Issue: 13(4), P. 475 - 475

Published: March 26, 2023

In developed countries, aging is often seen as typical, but it made complicated by many disorders and co-morbidities. Insulin resistance seems to be an underlying pathomechanism in frailty metabolic syndromes. The decline insulin sensitivity leads changes the oxidant–antioxidant balance accelerated inflammatory response, especially adipocytes macrophages adipose tissue, well muscle mass density. Thus, pathophysiology of syndemic disorders—the syndrome syndrome—an extremely important role may played increased oxidative stress pro-inflammatory state. Papers included this review explored available full texts reference lists relevant studies from last 20 years, before end 2022; we also investigated PubMed Google Scholar electronic databases. online resources describing elderly population (≥65 years old) published were searched for following terms: “oxidative and/or inflammation”, “frailty syndrome”. Then, all analyzed narratively described context inflammation markers which underlie pathomechanisms syndromes patients. So far, different pathways discussed show that a similar pathogenesis underlies development acceleration inflammation. argue syndemia represents two sides same coin.

Language: Английский

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Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(9)

Published: Aug. 20, 2022

Abstract The antagonistic pleiotropy hypothesis is a well-known evolutionary theory to explain the aging process. It proposes that while particular gene may possess beneficial effects during development, it can exert deleterious properties in aryl hydrocarbon receptor (AhR) has significant role embryogenesis, but later life, promotes several age-related degenerative processes. For instance, AhR factor (i) controls pluripotency of stem cells and stemness cancer cells, (ii) enhances differentiation embryonal especially signaling modulates hematopoietic progenitor (iii) also stimulates immunosuppressive Tregs, Bregs, M2 macrophages, finally, (iv) participates many peripheral tissues. On other hand, involved processes promoting cellular senescence pathological processes, e.g., osteoporosis, vascular dysfunction, remodeling immune system. Moreover, inhibits autophagy aggravates extracellular matrix degeneration. oxidative stress, excessive sphingolipid synthesis, disturbs energy metabolism by catabolizing NAD + degradation. based on complex diverse connections with major pathways context-dependent manner. regulatory steps include, specific ligand-dependent activation, modulation both genetic non-genetic responses, competition crosstalk transcription factors, such as ARNT, HIF-1α, E2F1, NF-κB, epigenetic regulation target genes binding partners. Thus, not only mTOR demonstrates

Language: Английский

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Cellular senescence in normal and adverse pregnancy

Reproductive Biology, Journal Year: 2023, Volume and Issue: 23(1), P. 100734 - 100734

Published: Feb. 9, 2023

Language: Английский

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Dynamic Alteration Profile and New Role of RNA m6A Methylation in Replicative and H2O2-Induced Premature Senescence of Human Embryonic Lung Fibroblasts

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9271 - 9271

Published: Aug. 17, 2022

N6-methyladenosine (m6A) methylation is one of the most common RNA modifications, regulating fate at posttranscriptional level, and closely related to cellular senescence. Both models replicative premature senescence induced by hydrogen peroxide (H2O2) were used detect m6A regulation during human embryonic lung fibroblasts (HEFs). The ROS level accumulated gradually with senescence, leading normal H2O2-treated cells had dramatically increased inducing onset acute Compared changed expression profiles for m6A-related enzymes binding proteins, including higher levels METTL3, METTL14, WTAP, KIAA1429, FTO, lower METTL16, ALKBH5, YTHDC1, YTHDF1/2/3 in persistence group, respectively. Meanwhile, senescent decreased total content activity, regardless or Moreover, specific regulated SIRT3, IRS2, E2F3 between separately. Taken together, differential epitranscription microenvironment targeted genes can be as epigenetic biomarkers cell diseases, offering new clues prevention intervention

Language: Английский

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Nano-Immunomodulation: A New Strategy for Skeletal Muscle Diseases and Aging?

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1175 - 1175

Published: Jan. 7, 2023

The skeletal muscle has a very remarkable ability to regenerate upon injury under physiological conditions; however, this regenerative capacity is strongly diminished in physio-pathological conditions, such as those present diseased or aged muscles. Many muscular dystrophies (MDs) are characterized by aberrant inflammation due the deregulation of both lymphoid and myeloid cell populations production pro-inflammatory cytokines. Pathological also observed old muscles systemic change immune system, known "inflammaging". Immunomodulation represents, therefore, promising therapeutic opportunity for different conditions. However, use immunomodulatory drugs clinics presents several caveats, including their low stability vivo, need high doses obtain therapeutically relevant effects, presence strong side effects. Within context, emerging field nanomedicine provides powerful tools needed control response. Nano-scale materials currently being explored biocarriers release agents damaged tissues, allowing with limited off-target In addition, intrinsic properties some nanomaterials offer further opportunities intervention that still be systematically explored. Here we exhaustively review state-of-the-art regarding nano-sized modulate response characterizes MDs sarcopenia (the age-dependent loss mass). Based on our learnings from cancer tolerance induction, discuss opportunities, challenges, limitations nano-immunomodulation.

Language: Английский

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The role of different physical exercises as an anti-aging factor in different stem cells

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: Feb. 26, 2025

Language: Английский

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