bims-agimec Biomed News
on Aging mechanisms
Issue of 2024‒07‒14
thirteen papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. The Changes of Mitochondria during Aging and Regeneration.
  2. Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.
  3. The Gut and Skin Microbiome and Its Association with Aging Clocks.
  4. Mitochondrial Quality Control Processes at the Crossroads of Cell Death and Survival: Mechanisms and Signaling Pathways.
  5. Aging of the eye: Lessons from cataracts and age-related macular degeneration.
  6. The Role of PGC-1α in Aging Skin Barrier Function.
  7. Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.
  8. How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation.
  9. Aging-related changes in the mechanical properties of single cells.
  10. The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity.
  11. Diabetes and Parkinson's Disease: Understanding Shared Molecular Mechanisms.
  12. Harnessing autophagy: A potential breakthrough in digestive disease treatment.
  13. [Theories of biological aging: An integrative review].
  1. Adv Biol (Weinh). 2024 Jul 09. e2300445
    The Changes of Mitochondria during Aging and Regeneration.
    Anqi Li, Yuan Qin, Guohua Gong.
      Aging and regeneration are opposite cellular processes. Aging refers to progressive dysfunction in most cells and tissues, and regeneration refers to the replacement of damaged or dysfunctional cells or tissues with existing adult or somatic stem cells. Various studies have shown that aging is accompanied by decreased regenerative abilities, indicating a link between them. The performance of any cellular process needs to be supported by the energy that is majorly produced by mitochondria. Thus, mitochondria may be a link between aging and regeneration. It should be interesting to discuss how mitochondria behave during aging and regeneration. The changes of mitochondria in aging and regeneration discussed in this review can provide a timely and necessary study of the causal roles of mitochondrial homeostasis in longevity and health.
    Keywords:  mitochondrial homeostasis; mitochondrial oxidative respiration; mtROS; regeneration; senescence
    DOI:  https://doi.org/10.1002/adbi.202300445
  2. Int J Mol Sci. 2024 Jul 05. pii: 7411. [Epub ahead of print]25(13):
    Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.
    Merin Lawrence, Abhishek Goyal, Shelly Pathak, Payal Ganguly.
      Advancing age is associated with several age-related diseases (ARDs), with musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic conditions contributing towards considerable number of patients, a deeper understanding of bone aging is the need of the hour. One of the underlying factors of bone aging is cellular senescence and its associated senescence associated secretory phenotype (SASP). SASP comprises of pro-inflammatory markers, cytokines and chemokines that arrest cell growth and development. The accumulation of SASP over several years leads to chronic low-grade inflammation with advancing age, also known as inflammaging. The pathways and molecular mechanisms focused on bone senescence and inflammaging are currently limited but are increasingly being explored. Most of the genes, pathways and mechanisms involved in senescence and inflammaging coincide with those associated with cancer and other ARDs like osteoarthritis (OA). Thus, exploring these pathways using techniques like sequencing, identifying these factors and combatting them with the most suitable approach are crucial for healthy aging and the early detection of ARDs. Several approaches can be used to aid regeneration and reduce senescence in the bone. These may be pharmacological, non-pharmacological and lifestyle interventions. With increasing evidence towards the intricate relationship between aging, senescence, inflammation and ARDs, these approaches may also be used as anti-aging strategies for the aging bone marrow (BM).
    Keywords:  aging; anti-aging strategies; bone; bone regeneration; cellular senescence; inflammaging; seno-therapeutics; therapeutic interventions
    DOI:  https://doi.org/10.3390/ijms25137411
  3. Int J Mol Sci. 2024 Jul 08. pii: 7471. [Epub ahead of print]25(13):
    The Gut and Skin Microbiome and Its Association with Aging Clocks.
    Mildred Min, Caitlin Egli, Raja K Sivamani.
      Aging clocks are predictive models of biological age derived from age-related changes, such as epigenetic changes, blood biomarkers, and, more recently, the microbiome. Gut and skin microbiota regulate more than barrier and immune function. Recent studies have shown that human microbiomes may predict aging. In this narrative review, we aim to discuss how the gut and skin microbiomes influence aging clocks as well as clarify the distinction between chronological and biological age. A literature search was performed on PubMed/MEDLINE databases with the following keywords: "skin microbiome" OR "gut microbiome" AND "aging clock" OR "epigenetic". Gut and skin microbiomes may be utilized to create aging clocks based on taxonomy, biodiversity, and functionality. The top contributing microbiota or metabolic pathways in these aging clocks may influence aging clock predictions and biological age. Furthermore, gut and skin microbiota may directly and indirectly influence aging clocks through the regulation of clock genes and the production of metabolites that serve as substrates or enzymatic regulators. Microbiome-based aging clock models may have therapeutic potential. However, more research is needed to advance our understanding of the role of microbiota in aging clocks.
    Keywords:  aging clocks; biological age; chronological age; epigenetic; metagenomic; microbiome
    DOI:  https://doi.org/10.3390/ijms25137471
  4. Int J Mol Sci. 2024 Jul 03. pii: 7305. [Epub ahead of print]25(13):
    Mitochondrial Quality Control Processes at the Crossroads of Cell Death and Survival: Mechanisms and Signaling Pathways.
    Emanuele Marzetti, Riccardo Calvani, Francesco Landi, Helio José Coelho-Júnior, Anna Picca.
      Biological aging results from an accumulation of damage in the face of reduced resilience. One major driver of aging is cell senescence, a state in which cells remain viable but lose their proliferative capacity, undergo metabolic alterations, and become resistant to apoptosis. This is accompanied by complex cellular changes that enable the development of a senescence-associated secretory phenotype (SASP). Mitochondria, organelles involved in energy provision and activities essential for regulating cell survival and death, are negatively impacted by aging. The age-associated decline in mitochondrial function is also accompanied by the development of chronic low-grade sterile inflammation. The latter shares some features and mediators with the SASP. Indeed, the unloading of damage-associated molecular patterns (DAMPs) at the extracellular level can trigger sterile inflammatory responses and mitochondria can contribute to the generation of DAMPs with pro-inflammatory properties. The extrusion of mitochondrial DNA (mtDNA) via mitochondrial outer membrane permeabilization under an apoptotic stress triggers senescence programs. Additional pathways can contribute to sterile inflammation. For instance, pyroptosis is a caspase-dependent inducer of systemic inflammation, which is also elicited by mtDNA release and contributes to aging. Herein, we overview the molecular mechanisms that may link mitochondrial dyshomeostasis, pyroptosis, sterile inflammation, and senescence and discuss how these contribute to aging and could be exploited as molecular targets for alleviating the cell damage burden and achieving healthy longevity.
    Keywords:  DAMPs; SASP; cell death; extracellular vesicles; inflammaging; interleukin; mitochondrial quality control; mitochondrial-derived vesicles; mtDNA; pyroptosis
    DOI:  https://doi.org/10.3390/ijms25137305
  5. Ageing Res Rev. 2024 Jul 06. pii: S1568-1637(24)00225-3. [Epub ahead of print]99 102407
    Aging of the eye: Lessons from cataracts and age-related macular degeneration.
    Ales Cvekl, Jan Vijg.
      Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand the effects of the aging process on these diseases, including the genetic, molecular, and cellular mechanisms that underlie the increased risk of disease over the lifetime. Understanding of the aging eye increases general knowledge of the cellular physiology impacted by aging processes at various biological extremes. Two major diseases, age-related cataract and age-related macular degeneration (AMD) are caused by dysfunction of the lens and retina, respectively. Lens transparency and light refraction are mediated by lens fiber cells lacking nuclei and other organelles, which provides a unique opportunity to study a single aging hallmark, i.e., loss of proteostasis, within an environment of limited metabolism. In AMD, local dysfunction of the photoreceptors/retinal pigmented epithelium/Bruch's membrane/choriocapillaris complex in the macula leads to the loss of photoreceptors and eventually loss of central vision, and is driven by nearly all the hallmarks of aging and shares features with Alzheimer's disease, Parkinson's disease, cardiovascular disease, and diabetes. The aging eye can function as a model for studying basic mechanisms of aging and, vice versa, well-defined hallmarks of aging can be used as tools to understand age-related eye disease.
    Keywords:  Age-related macular degeneration; age-related cataract; crystallins; fovea; lens; macula; retinal pigmented epithelium
    DOI:  https://doi.org/10.1016/j.arr.2024.102407
  6. Cells. 2024 Jul 02. pii: 1135. [Epub ahead of print]13(13):
    The Role of PGC-1α in Aging Skin Barrier Function.
    Yonghong Luo, Wendy B Bollag.
      Skin provides a physical and immune barrier to protect the body from foreign substances, microbial invasion, and desiccation. Aging reduces the barrier function of skin and its rate of repair. Aged skin exhibits decreased mitochondrial function and prolonged low-level inflammation that can be seen in other organs with aging. Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), an important transcriptional coactivator, plays a central role in modulating mitochondrial function and antioxidant production. Mitochondrial function and inflammation have been linked to epidermal function, but the mechanisms are unclear. The aim of this review is to discuss the mechanisms by which PGC-1α might exert a positive effect on aged skin barrier function. Initially, we provide an overview of the function of skin under physiological and aging conditions, focusing on the epidermis. We then discuss mitochondrial function, oxidative stress, cellular senescence, and inflamm-aging, the chronic low-level inflammation observed in aging individuals. Finally, we discuss the effects of PGC-1α on mitochondrial function, as well as the regulation and role of PGC-1α in the aging epidermis.
    Keywords:  aging; antioxidant defense; coactivator; epidermis; keratinocytes; melanocytes; mitochondria; permeability barrier; skin; wound healing
    DOI:  https://doi.org/10.3390/cells13131135
  7. Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul 08.
    Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.
    Shagufta Kamal, Sharon Babar, Waqas Ali, Kanwal Rehman, Amjad Hussain, Muhammad Sajid Hamid Akash.
      The greatest challenges that organisms face today are effective responses or detection of life-threatening environmental changes due to an obvious semblance of stress and metabolic fluctuations. These are associated with different pathological conditions among which cancer is most important. Sirtuins (SIRTs; NAD+-dependent enzymes) are versatile enzymes with diverse substrate preferences, cellular locations, crucial for cellular processes and pathological conditions. This article describes in detail the distinct roles of SIRT isoforms, unveiling their potential as either cancer promoters or suppressors and also explores how both natural and synthetic compounds influence the SIRT function, indicating promise for therapeutic applications. We also discussed the inhibitors/activators tailored to specific SIRTs, holding potential for diseases lacking effective treatments. It may uncover the lesser-studied SIRT isoforms (e.g., SIRT6, SIRT7) and their unique functions. This article also offers a comprehensive overview of SIRTs, linking them to a spectrum of diseases and highlighting their potential for targeted therapies, combination approaches, disease management, and personalized medicine. We aim to contribute to a transformative era in healthcare and innovative treatments by unraveling the intricate functions of SIRTs.
    Keywords:  Cancer promoters or suppressor; Disease management; Sirtuins; Therapeutic intervention
    DOI:  https://doi.org/10.1007/s00210-024-03263-9
  8. Heliyon. 2024 Jun 30. 10(12): e32831
    How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation.
    Christopher Wells, Tristan Robertson, Prameet Sheth, Sheela Abraham.
      The gut microbiome has come to prominence across research disciplines, due to its influence on major biological systems within humans. Recently, a relationship between the gut microbiome and hematopoietic system has been identified and coined the gut-bone marrow axis. It is well established that the hematopoietic system and gut microbiome separately alter with age; however, the relationship between these changes and how these systems influence each other demands investigation. Since the hematopoietic system produces immune cells that help govern commensal bacteria, it is important to identify how the microbiome interacts with hematopoietic stem cells (HSCs). The gut microbiota has been shown to influence the development and outcomes of hematologic disorders, suggesting dysbiosis may influence the maintenance of HSCs with age. Short chain fatty acids (SCFAs), lactate, iron availability, tryptophan metabolites, bacterial extracellular vesicles, microbe associated molecular patterns (MAMPs), and toll-like receptor (TLR) signalling have been proposed as key mediators of communication across the gut-bone marrow axis and will be reviewed in this article within the context of aging.
    Keywords:  Aging; Gut dysbiosis; Hematologic disorders; Hematopoietic stem cells; Inflammation; Microbiome; Stem cell regulation
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e32831
  9. Heliyon. 2024 Jun 30. 10(12): e32974
    Aging-related changes in the mechanical properties of single cells.
    Amarnath Singam, Chandrabali Bhattacharya, Seungman Park.
      Mechanical properties, along with biochemical and molecular properties, play crucial roles in governing cellular function and homeostasis. Cellular mechanics are influenced by various factors, including physiological and pathological states, making them potential biomarkers for diseases and aging. While several methods such as AFM, particle-tracking microrheology, optical tweezers/stretching, magnetic tweezers/twisting cytometry, microfluidics, and micropipette aspiration have been widely utilized to measure the mechanical properties of single cells, our understanding of how aging affects these properties remains limited. To fill this knowledge gap, we provide a brief overview of the commonly used methods to measure single-cell mechanical properties. We then delve into the effects of aging on the mechanical properties of different cell types. Finally, we discuss the importance of studying cellular viscous and viscoelastic properties as well as aging induced by different stressors to gain a deeper understanding of the aging process and aging-related diseases.
    Keywords:  Aging; Cell; Cytoskeleton; Elastic property; F-actin; Mechanical property; Stress fiber; Viscous property
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e32974
  10. Int J Mol Sci. 2024 Jun 27. pii: 7013. [Epub ahead of print]25(13):
    The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity.
    Sidharth S Jain, Giselle Burton Sojo, Harry Sun, Benjamin N Friedland, Megan E McNamara, Marcel O Schmidt, Anton Wellstein.
      Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system, on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.
    Keywords:  aging; cellular senescence; immune checkpoint inhibitor; immune-related adverse events
    DOI:  https://doi.org/10.3390/ijms25137013
  11. J Parkinsons Dis. 2024 Jun 29.
    Diabetes and Parkinson's Disease: Understanding Shared Molecular Mechanisms.
    Annekatrin König, Tiago F Outeiro.
      Aging is a major risk factor for Parkinson's disease (PD). Genetic mutations account for a small percentage of cases and the majority appears to be sporadic, with yet unclear causes. However, various environmental factors have been linked to an increased risk of developing PD and, therefore, understanding the complex interplay between genetic and environmental factors is crucial for developing effective disease-modifying therapies. Several studies identified a connection between type 2 diabetes (T2DM) and PD. T2DM is characterized by insulin resistance and failure of β-cells to compensate, leading to hyperglycemia and serious comorbidities. Both PD and T2DM share misregulated processes, including mitochondrial dysfunction, oxidative stress, chronic inflammation, altered proteostasis, protein aggregation, and misregulation of glucose metabolism. Chronic or recurring hyperglycemia is a T2DM hallmark and can lead to increased methylglyoxal (MGO) production, which is responsible for protein glycation. Glycation of alpha-synuclein (aSyn), a central player in PD pathogenesis, accelerates the deleterious aSyn effects. Interestingly, MGO blood plasma levels and aSyn glycation are significantly elevated in T2DM patients, suggesting a molecular mechanism underlying the T2DM - PD link. Compared to high constant glucose levels, glycemic variability (fluctuations in blood glucose levels), can be more detrimental for diabetic patients, causing oxidative stress, inflammation, and endothelial damage. Accordingly, it is imperative for future research to prioritize the exploration of glucose variability's influence on PD development and progression. This involves moving beyond the binary classification of patients as diabetic or non-diabetic, aiming to pave the way for the development of enhanced therapeutic interventions.
    Keywords:  Parkinson’s disease; alpha-synuclein; diabetes; glycation; neurodegeneration
    DOI:  https://doi.org/10.3233/JPD-230104
  12. World J Gastroenterol. 2024 Jun 28. 30(24): 3036-3043
    Harnessing autophagy: A potential breakthrough in digestive disease treatment.
    Mukaddes Esrefoglu.
      Autophagy, a conserved cellular degradation process, is crucial for various cellular processes such as immune responses, inflammation, metabolic and oxidative stress adaptation, cell proliferation, development, and tissue repair and remodeling. Dysregulation of autophagy is suspected in numerous diseases, including cancer, neurodegenerative diseases, digestive disorders, metabolic syndromes, and infectious and inflammatory diseases. If autophagy is disrupted, for example, this can have serious consequences and lead to chronic inflammation and tissue damage, as occurs in diseases such as Chron's disease and ulcerative colitis. On the other hand, the influence of autophagy on the development and progression of cancer is not clear. Autophagy can both suppress and promote the progression and metastasis of cancer at various stages. From inflammatory bowel diseases to gastrointestinal cancer, researchers are discovering the intricate role of autophagy in maintaining gut health and its potential as a therapeutic target. Researchers should carefully consider the nature and progression of diseases such as cancer when trying to determine whether inhibiting or stimulating autophagy is likely to be beneficial. Multidisciplinary approaches that combine cutting-edge research with clinical expertise are key to unlocking the full therapeutic potential of autophagy in digestive diseases.
    Keywords:  Autophagy; Digestive disease; Gastrointestinal cancer; Harnessing autophagy; Inflammatory bowel disease
    DOI:  https://doi.org/10.3748/wjg.v30.i24.3036
  13. Rev Esp Geriatr Gerontol. 2024 Jul 11. pii: S0211-139X(24)00064-7. [Epub ahead of print]59(6): 101530
    [Theories of biological aging: An integrative review].
    Fabián Aníbal Quintero, Mariela Garraza, Bárbara Navazo, María Florencia Cesani.
      In this article, we review the main theories of biological aging, exploring the interaction of genetic, epigenetic, metabolic, immunological, and ecological factors in this process. For this purpose, we examine and discuss theories such as the allocation of metabolic resources, pleiotropic antagonism, genetic regulation, codon restriction, replicative senescence, action of free radicals, caloric restriction, catastrophic error, immunological theory, neuroendocrine theory, programmed aging, epigenetics of aging, grandmother and caregiver theories and ecological biophysical theory. We identify the contribution of different biological mechanisms to aging, emphasizing the complementarity of theories such as the allocation of metabolic resources, pleiotropic antagonism, and caloric restriction, providing a more comprehensive view of the phenomenon. In conclusion, we highlight the need to consider diverse perspectives in aging research, recognizing the absence of a single explanation. Integrating these theories is crucial to comprehensively understand the process and develop effective interventions in health and well-being in old age.
    Keywords:  Biological aging; Envejecimiento biológico; Human longevity; Longevidad humana; Teorías; Theories
    DOI:  https://doi.org/10.1016/j.regg.2024.101530
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