bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–09–29
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. The role of p21 in cellular senescence and aging-related diseases.
  2. Elucidating the Role of Sirtuin 3 in Mammalian Oocyte Aging.
  3. Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets.
  4. The role of mitochondria in cytokine and chemokine signalling during ageing.
  5. The putative contribution of cellular senescence to driving tauopathies.
  6. The impact of opioids on the hallmarks of ageing.
  7. Impact of gut microbiota on cardiac aging.
  1. Mol Cells. 2024 Sep 18. pii: S1016-8478(24)00138-9. [Epub ahead of print] 100113
    The role of p21 in cellular senescence and aging-related diseases.
    Jiayu Yan, Siyi Chen, Zimei Yi, Ruowen Zhao, Jiayu Zhu, Shuwen Ding, Junhua Wu.
      During the aging process or disease progression, normal cells and tissues in the body undergo various stresses, leading to cell damage and the need for repair, adaptation, apoptosis, or defense responses. Cellular senescence is a key player in this process, influencing the rate of aging and disease progression. It can be triggered by different stress factors, resulting in irreversible cell cycle arrest and functional decline. Senescent cells often show high expression of cell cycle factors like p21 and p16, which are involved in cell cycle arrest. p16 has long been recognized as a significant marker of aging. Recent evidence suggests that p21high cells and p16high cells represent distinct cell populations in terms of cell type, tissue location, accumulation kinetics, and physiological functions. This article focuses on recent advancements in understanding p21-dependent cellular senescence. It starts by providing an overview of the role of p21 in three primary cellular senescence phenotypes where it plays a crucial role. It then delves into the pathogenesis of diseases closely linked to p21-dependent cellular senescence, particularly metabolic disorders and cardiovascular diseases. The article also discusses progress in p21-related animal models and outlines strategies for utilizing p21 to intervene in cellular senescence by delaying aging, eliminating senescent cells, and rejuvenating senescent cells. This review systematically examines the pathogenesis of p21-dependent cellular senescence, emphasizing its importance in studying aging heterogeneity and developing new senolytic therapies. It aims to stimulate future research on leveraging p21 to enhance the characteristics of senescent cells, allowing more precise methods for eliminating harmful senescent cells at the right time, thereby delaying aging and potentially achieving rejuvenation.
    Keywords:  aging-related diseases; cellular senescence; p21; senolytic; senomorphic
    DOI:  https://doi.org/10.1016/j.mocell.2024.100113
  2. Cells. 2024 Sep 22. pii: 1592. [Epub ahead of print]13(18):
    Elucidating the Role of Sirtuin 3 in Mammalian Oocyte Aging.
    Pawel Kordowitzki.
      The field of reproductive biology has made significant progress in recent years, identifying specific molecular players that influence oocyte development and function. Among them, sirtuin 3 (SIRT3) has attracted particular attention for its central role in mediating mitochondrial function and cellular stress responses in oocytes. So far, studies have demonstrated that the knockdown of SIRT3 leads to a decrease in blastocyst formation and an increase in oxidative stress within an embryo, underscoring the importance of SIRT3 in maintaining the cellular redox balance critical for embryonic survival and growth. Furthermore, the literature reveals specific signaling pathways, such as the SIRT3- Glycogen synthase kinase-3 beta (GSK3β) deacetylation pathway, crucial for mitigating oxidative stress-related anomalies in oocyte meiosis, particularly under conditions like maternal diabetes. Overall, the emerging role of SIRT3 in regulating oocyte mitochondrial function and development highlights the critical importance of understanding the intricate connections between cellular metabolism, stress response pathways, and overall reproductive health and function. This knowledge could lead to the development of novel strategies to support oocyte quality and fertility, with far-reaching implications for assisted reproductive technologies and women's healthcare. This commentary aims to provide an overview of the importance of SIRT3 in oocytes by synthesizing results from a multitude of studies. The aim is to elucidate the role of SIRT3 in oocyte development, maturation, and aging and to identify areas where further research is needed.
    Keywords:  SIRT3; aging; egg; embryo; mitochondria; oocyte; reproductive aging; sirtuin 3
    DOI:  https://doi.org/10.3390/cells13181592
  3. Mol Aspects Med. 2024 Sep 22. pii: S0098-2997(24)00078-5. [Epub ahead of print]100 101319
    Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets.
    Mercedes Grima-Terrén, Silvia Campanario, Ignacio Ramírez-Pardo, Andrés Cisneros, Xiaotong Hong, Eusebio Perdiguero, Antonio L Serrano, Joan Isern, Pura Muñoz-Cánoves.
      Sarcopenia is a progressive muscle wasting disorder that severely impacts the quality of life of elderly individuals. Although the natural aging process primarily causes sarcopenia, it can develop in response to other conditions. Because muscle function is influenced by numerous changes that occur with age, the etiology of sarcopenia remains unclear. However, recent characterizations of the aging muscle transcriptional landscape, signaling pathway disruptions, fiber and extracellular matrix compositions, systemic metabolomic and inflammatory responses, mitochondrial function, and neurological inputs offer insights and hope for future treatments. This review will discuss age-related changes in healthy muscle and our current understanding of how this can deteriorate into sarcopenia. As our elderly population continues to grow, we must understand sarcopenia and find treatments that allow individuals to maintain independence and dignity throughout an extended lifespan.
    Keywords:  Aging; Atrophy; Proteostasis; Sarcopenia; Skeletal muscle
    DOI:  https://doi.org/10.1016/j.mam.2024.101319
  4. Mech Ageing Dev. 2024 Sep 20. pii: S0047-6374(24)00093-9. [Epub ahead of print]222 111993
    The role of mitochondria in cytokine and chemokine signalling during ageing.
    Maria Kalykaki, Teresa Rubio-Tomás, Nektarios Tavernarakis.
      Ageing is accompanied by a persistent, low-level inflammation, termed "inflammageing", which contributes to the pathogenesis of age-related diseases. Mitochondria fulfil multiple roles in host immune responses, while mitochondrial dysfunction, a hallmark of ageing, has been shown to promote chronic inflammatory states by regulating the production of cytokines and chemokines. In this review, we aim to disentangle the molecular mechanisms underlying this process. We describe the role of mitochondrial signalling components such as mitochondrial DNA, mitochondrial RNA, N-formylated peptides, ROS, cardiolipin, cytochrome c, mitochondrial metabolites, potassium efflux and mitochondrial calcium in the age-related immune system activation. Furthermore, we discuss the effect of age-related decline in mitochondrial quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy and UPRmt, in inflammatory states upon ageing. In addition, we focus on the dynamic relationship between mitochondrial dysfunction and cellular senescence and its role in regulating the secretion of pro-inflammatory molecules by senescent cells. Finally, we review the existing literature regarding mitochondrial dysfunction and inflammation in specific age-related pathological conditions, including neurodegenerative diseases (Alzheimer's and Parkinson's disease, and amyotrophic lateral sclerosis), osteoarthritis and sarcopenia.
    Keywords:  Age-related disease; Chemokine; Cytokine; Inflammageing; Mitochondrial dysfunction; Senescence
    DOI:  https://doi.org/10.1016/j.mad.2024.111993
  5. Trends Immunol. 2024 Sep 20. pii: S1471-4906(24)00192-3. [Epub ahead of print]
    The putative contribution of cellular senescence to driving tauopathies.
    Deniz Karabag, Michael T Heneka, Christina Ising.
      During mammalian aging, senescent cells accumulate in the body. Recent evidence suggests that senescent cells potentially contribute to age-related neurodegenerative diseases in the central nervous system (CNS), including tauopathies such as Alzheimer's disease (AD). Senescent cells undergo irreversible cell cycle arrest and release an inflammatory 'senescence-associated secretory profile' (SASP), which can exert devastating effects on surrounding cells. Senescent markers and SASP factors have been detected in multiple brain cells in tauopathies, including microglia, astrocytes, and perhaps even post-mitotic neurons, possibly contributing to the initiation as well as progression of these diseases. Here, we discuss the implications of presenting a senescent phenotype in tauopathies and highlight a potential role for the NOD-like receptor protein 3 (NLRP3) inflammasome as a newfound mechanism implicated in senescence and SASP formation.
    Keywords:  Alzheimer’s disease; aging; cellular senescence; senescence-associated secretory phenotype; tauopathies
    DOI:  https://doi.org/10.1016/j.it.2024.08.006
  6. Mech Ageing Dev. 2024 Sep 24. pii: S0047-6374(24)00094-0. [Epub ahead of print] 111994
    The impact of opioids on the hallmarks of ageing.
    Ana Rita Tavares Henriques, João Pedro Silva, Félix Carvalho.
      Opioids rank among the most hazardous substances of abuse, leading to opioid use disorders (which greatly diminish life quality) and contributing to the highest drug-related mortality rates. Nonetheless, both the therapeutic and recreational use of opioids is escalating globally. Interestingly, chronic opioid users often exhibit signs consistent with accelerated ageing, suggesting that they likely interfere with well-characterized ageing mechanisms (e.g., telomere shortening, epigenetic changes, mitochondrial dysfunction, cellular senescence). Here, we review the most recent advances regarding the impact of opioids on well-characterized hallmarks of ageing, to ascertain a potential association between opioid use and accelerated ageing. Our findings indicate that there is accumulating evidence supporting a close association between the use of opioids and the early onset of some ageing hallmarks, namely mitochondrial dysfunction, genomic instability, or telomere shortening. However, there is still limited data available regarding how opioids specifically impact other ageing hallmarks, like nutrient sensing, cellular senescence, or loss of proteostasis. Taking into consideration the high prevalence of opioid use, strengthening the understanding of the mechanisms underlying opioids' impact on ageing assumes utmost relevance, both in terms of improving risk assessment, as well as to help researchers and clinicians prevent or mitigate these effects in clinical settings.
    Keywords:  Accelerated ageing; Cellular senescence; Genomic instability; Inflammation; Oxidative stress; Telomere shortening
    DOI:  https://doi.org/10.1016/j.mad.2024.111994
  7. Arch Gerontol Geriatr. 2024 Sep 13. pii: S0167-4943(24)00315-7. [Epub ahead of print]128 105639
    Impact of gut microbiota on cardiac aging.
    Zhiyi Yin, Liyao Fu, Yongjun Wang, Shi Tai.
      Recent research has suggested imbalances in gut microbiota composition as contributors to cardiac aging. An individual's physical condition, along with lifestyle-associated factors, including diet and medication, are significant determinants of gut microbiota composition. This review discusses evidence of bidirectional associations between aging and gut microbiota, identifying gut microbiota-derived metabolites as potential regulators of cardiac aging. It summarizes the effects of gut microbiota on cardiac aging diseases, including cardiac hypertrophy and fibrosis, heart failure, and atrial fibrillation. Furthermore, this review discusses the potential anti-aging effects of modifying gut microbiota composition through dietary and pharmacological interventions. Lastly, it underscores critical knowledge gaps and outlines future research directions. Given the current limited understanding of the direct relationship between gut microbiota and cardiac aging, there is an urgent need for preclinical and clinical investigations into the mechanistic interactions between gut microbiota and cardiac aging. Such endeavors hold promise for shedding light on the pathophysiology of cardiac aging and uncovering new therapeutic targets for cardiac aging diseases.
    Keywords:  Anti-aging effects; Cardiac aging; Gut microbiota; Lifestyle; Metabolites
    DOI:  https://doi.org/10.1016/j.archger.2024.105639
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