bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2023‒12‒10
six papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño



  1. Proc Biol Sci. 2023 Dec 06. 290(2012): 20232093
      Epigenetic alterations are a primary hallmark of ageing. In mammals, age-related epigenetic changes alter gene expression profiles, disrupt cellular homeostasis and physiological functions and, therefore, promote ageing. It remains unclear whether ageing is also driven by epigenetic mechanisms in invertebrates. Here, we used a pharmacological hypomethylating agent (RG108) to evaluate the effects of DNA methylation (DNAme) on lifespan in an insect-the bumblebee Bombus terrestris. RG108 extended mean lifespan by 43% and induced the differential methylation of genes involved in hallmarks of ageing, including DNA damage repair and chromatin organization. Furthermore, the longevity gene sirt1 was overexpressed following the treatment. Functional experiments demonstrated that SIRT1 protein activity was positively associated with lifespan. Overall, our study indicates that epigenetic mechanisms are conserved regulators of lifespan in both vertebrates and invertebrates and provides new insights into how DNAme is involved in the ageing process in insects.
    Keywords:  DNA methylation; ageing; bumblebee; epigenetics; insects; sirtuins
    DOI:  https://doi.org/10.1098/rspb.2023.2093
  2. Nat Aging. 2023 Dec 04.
      DNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We developed a statistically robust framework to compare methylation rates at conserved age-related sites across mammals. We found that methylation rates negatively scale with maximum lifespan in both blood and skin. The emergence of explicit scaling suggests that methylation rates are, or are linked to, an evolutionary constraint on maximum lifespan acting across diverse mammalian lineages.
    DOI:  https://doi.org/10.1038/s43587-023-00535-6
  3. Free Radic Biol Med. 2023 Nov 30. pii: S0891-5849(23)01130-9. [Epub ahead of print]210 304-317
      Persistent oxidative stress and endoplasmic reticulum (ER) stress are the primary mechanisms of age-related cardiovascular diseases. Although exercise training is viewed as an effective anti-aging approach, further exploration is needed to identify the mechanisms and functional targets. In this study, the impact of resistance training (RT) on the expression of Smyd1, the levels of reactive oxygen species (ROS) and the expression of ER stress-related protein in the hearts of mice of different ages were assessed. In addition, the role of Smyd1 in the aging-induced oxidative stress and ER stress were evaluated in d-galactose (D-gal)-treated H9C2 cells. We demonstrated that RT in middle age increased the expression of Smyd1 and restricted heart aging-induced ER stress. Overexpression of Smyd1 restrained oxidative stress and ER stress in D-gal-treated H9C2 cells, while the inhibition of Nrf2 and Smyd1 escalated ER stress. These findings demonstrate that Smyd1 has significant impact in regulating age-related ER stress. RT in middle age can up-regulates Smyd1 expression and inhibits oxidative stress and ER stress in the heart.
    Keywords:  Endoplasmic reticulum stress; Heart; Oxidative stress; Resistance training; Smyd1
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2023.11.029
  4. Aging (Albany NY). 2023 Dec 05. 15
      Cellular senescence plays a very important role in the ageing of organisms and age-related diseases that increase with age, a process that involves physiological, structural, biochemical and molecular changes in cells. In recent years, it has been found that the active ingredients of herbs and their natural products can prevent and control cellular senescence by affecting telomerase activity, oxidative stress response, autophagy, mitochondrial disorders, DNA damage, inflammatory response, metabolism, intestinal flora, and other factors. In this paper, we review the research information on the prevention and control of cellular senescence in Chinese herbal medicine through computer searches of PubMed, Web of Science, Science Direct and CNKI databases.
    Keywords:  Chinese herbal medicine; cellular senescence; inflammatory response; intestinal flora
    DOI:  https://doi.org/10.18632/aging.205269
  5. Osteoarthritis Cartilage. 2023 Dec 02. pii: S1063-4584(23)00997-4. [Epub ahead of print]
      OBJECTIVE: The correlation between age and incidence of osteoarthritis (OA) is well known but the causal mechanisms involved are not completely understood. This narrative review summarizes selected key findings from the past 30 years that have elucidated key aspects of the relationship between aging and OA.METHODS: The peer-reviewed English language literature was searched on PubMed using key words including senescence, aging, cartilage, and osteoarthritis, for original studies and reviews published from 1993-2023 with a major focus on more recent studies. Manuscripts most relevant to aging and OA that examined one or more of the hallmarks of aging were selected for further review.
    RESULTS: All proposed hallmarks of aging have been observed in articular cartilage and some have also been described in other joint tissues. Hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled macroautophagy, chronic inflammation, and dysbiosis. There is evidence that these age-related changes contribute to the development of OA in part by promoting cellular senescence. Senescence may therefore serve as a downstream mediator that connects numerous aging hallmarks to OA, likely through the senescence-associated secretory phenotype (SASP) that is characterized by increased production of proinflammatory cytokines and matrix metalloproteinases.
    CONCLUSIONS: Progress over the past 30 years has provided the foundation for emerging therapies, such as senolytics and senomorphics, that hold promise for OA disease modification. Mechanistic studies utilizing physiologically-aged animals and cadaveric human joint tissues will be important for continued progress.
    Keywords:  Aging; Chondrocyte; cartilage; senescence
    DOI:  https://doi.org/10.1016/j.joca.2023.11.018
  6. Nat Aging. 2023 Dec 05.
      For many pathologies associated with aging, female patients present with higher morbidity and more frequent adverse events from treatments compared to male patients. While preclinical models are the foundation of our mechanistic understanding of age-related diseases, the most common models fail to recapitulate archetypical female aging trajectories. For example, while over 70% of the top age-related diseases are influenced by the systemic effects of reproductive senescence, we found that preclinical studies that include menopausal phenotypes modeling those seen in humans make up <1% of published aging biology research. The long-term impacts of pregnancy, birthing and breastfeeding are also typically omitted from preclinical work. In this Perspective, we summarize limitations in the most commonly used aging models, and we provide recommendations for better incorporating menopause, pregnancy and other considerations of sex in vivo and in vitro. Lastly, we outline action items for aging biology researchers, journals, funding agencies and animal providers to address this gap.
    DOI:  https://doi.org/10.1038/s43587-023-00509-8