Translatability of life-extending pharmacological treatments between different species.

Anti-aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti-aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti-aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species-specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti-aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan.

Assessment of the Effect on Periodontitis of Antibiotic Therapy and Bacterial Lysate Treatment.

Periodontitis is an inflammatory process that starts with soft tissue inflammation caused by the intervention of oral bacteria. By modulating local immunity, it is possible to supplement or replace current therapeutic methods. The aim of this study was to compare the effects of an immunostimulatory treatment with the antibiotherapy usually applied to periodontitis patients. On a model of periodontitis induced in 30 rats (divided into three equal groups) with bacterial strains selected from the human oral microbiome (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis), we administered antibiotics, bacterial lysates and saline for 10 days. Clinically, no significant lesions were observed between the groups, but hematologically, we detected a decrease in lymphocyte and neutrophil counts in both the antibiotic and lysate-treated groups. Immunologically, IL-6 remained elevated compared to the saline group, denoting the body's effort to compensate for bone loss due to bacterial action. Histopathologically, the results show more pronounced oral tissue regeneration in the antibiotic group and a reduced inflammatory reaction in the lysate group. We can conclude that the proposed bacterial lysate has similar effects to antibiotic therapy and can be considered an option in treating periodontitis, thus eliminating the unnecessary use of antibiotics.

Induction of Experimental Peri-Implantitis with Strains Selected from the Human Oral Microbiome.

Peri-implantitis (PI), the most widespread condition in the oral cavity, affects patients globally; thus, advanced research in both in vitro and in vivo studies is required. This study aimed to develop peri-implantitis in the rat model by oral contamination with bacteria responsible for PI in humans. The study was carried out in three stages: the extraction of the maxillary first molar to reproduce the human edentation, the mounting of the implant, and finally, the contamination of the device by gavage with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis. The hematological examinations showed statistically significant increases for WBCs (white blood cells), Hb (hemoglobin), RBCs (red blood cells), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), and PLTs (platelets), but especially for the level of neutrophils and lymphocytes, and the systemic immunoinflammatory index completed the picture related to the inflammatory response triggered as a result of the activity of microorganisms pathogens on oral tissues. By examining the liver and kidney profile, we hypothesized that peri-implantitis is associated with systemic diseases, and the histopathological examination showed peri-implantitis lesions characterized by a marked inflammatory infiltrate with numerous neutrophils and lymphocytes. By corroborating all the results, we successfully developed a rat peri-implantitis model using a mixed bacterial infection through the oral gavage technique.

Epigenetics of Ageing and Psychiatric Disorders.

Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of diseases such as cancer, cardiovascular disorders, and psychiatric disorders. Numerous studies suggest a connection between epigenetic changes and mood disorders. In this study, we performed a comprehensive search using PubMed and Google for the terms "epigenetics", "ageing", "miRNA", "schizophrenia", and "mood disorders" in the titles and abstracts of articles. Epigenetic changes during early life may play a crucial role in triggering severe mental disorders and shaping their clinical trajectory. Although these alterations can take place at any age, their impact may not be immediately evident or observable until later in life. Epigenetic modifications play a crucial role in the ageing process and challenge the prevailing belief that mutations are the primary driver of ageing. However, it is plausible that these epigenetic changes are a consequence of the disorder rather than its root cause. Moreover, both the disorder and the epigenetic alterations may be influenced by shared environmental or genetic factors. In the near future, we might be able to replace chronological age with biological age, based on the epigenetic clock, with the promise of providing greater therapeutic benefits. A wide range of epigenetic drugs are currently under development at various stages. Although their full effectiveness is yet to be realized, they show great potential in the treatment of cancer, psychiatric disorders, and other complex diseases.

Induction of Periodontitis Using Bacterial Strains Isolated from the Human Oral Microbiome in an Experimental Rat Model.

Periodontal disease is that condition resulting in the destruction of periodontal tissues, bone resorption, and tooth loss, the etiology of which is linked to immunological and microbiological factors. The aim of this study was to evaluate the potential trigger of periodontal disease in a rat model using bacterial species incriminated in the pathology of human periodontitis and to establish their optimal concentrations capable of reproducing the disease, with the idea of subsequently developing innovative treatments for the condition. In this study, we included 15 male Wistar rats, aged 20 weeks, which we divided into three groups. In each group, we applied ligatures with gingival retraction wire on the maxillary incisors. The ligature and the gingival sac were contaminated by oral gavage with a mixture of fresh cultures of Aggregatibacter actinomycetemcomitans (A.a), Fusobacterium nucleatum (F.n) and Streptococcus oralis (S.o) in concentrations of 108, 109, and 1010 CFU/mL each for 5 days a week for 4 weeks. During the clinical monitoring period of 28 days, overlapped with the period of oral contamination, we followed the expression of clinical signs specific to periodontitis. We also monitored the evolution of body weight and took weekly samples from the oral cavity for the microbiological identification of the tested bacteria and blood samples for hematological examination. At the end of the study, the animals were euthanized, and the ligated incisors were taken for histopathological analysis. The characteristic symptomatology of periodontal disease was expressed from the first week of the study and was maintained until the end, and we were able to identify the bacteria during each examination. Hematologically, the number of neutrophils decreased dramatically (p < 0.0001) in the case of the 109 group, unlike the other groups, as did the number of lymphocytes. Histopathologically, we identified neutrophilic infiltrate in all groups, as well as the presence of coccobacilli, periodontal tissue hyperplasia, and periodontal lysis. In the 109 group, we also observed pulpal tissue with necrotic bone fragments and pyogranulomatous inflammatory reaction. By corroborating the data, we can conclude that for the development of periodontal disease using A.a, F.n, and S.o, a concentration of 109 or 1010 CFU/mL is required, which must necessarily contaminate a ligature thread applied to the level of the rat's dental pack.

Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism.

Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.