The small bowel microbiome changes significantly with age and aspects of the ageing process

Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer’s disease and Parkinson’s disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, using duodenal aspirates from 251 subjects aged 18-80 years. Differences included significantly decreased microbial diversity in older subjects, driven by increased relative abundance of phylum Proteobacteria, particularly family Enterobacteriaceae and coliform genera Escherichia and Klebsiella. Moreover, while this decreased diversity was associated with the ‘ageing process’ (comprising chronologic age, number of medications, and number of concomitant diseases), changes in certain taxa were found to be associated with number of medications alone (Klebsiella), number of diseases alone (Clostridium, Bilophila), or chronologic age alone (Escherichia, Lactobacillus, Enterococcus). Lastly, many taxa associated with increasing chronologic age were anaerobes. These changes may contribute to changes in human health that occur during the ageing process.

A Hypothesis: The Interplay of Exercise and Physiological Heterogeneity as Drivers of Human Ageing

As the inherent ageing process affects every facet of biology, physiology could be considered as the study of the healthy human ageing process. Where biological health is affected by lifestyle, the continual and continuing interaction of this process with physical activity and other lifestyle choices determine whether the ageing trajectory is toward health or disease. The presentation of both these states is further modified in individuals by the interaction of inherent physiological heterogeneity and the heterogeneity associated with responses and adaptions to exercise. The range of heterogeneity in healthy physiology is circumscribed by the necessity to conform to that of the human species. Our hypothesis is that, when sufficient exercise is present, these multiple interactions appear to produce an ageing profile that, while functional ability is in decline, remains synchronous, coherent, and integrated throughout most of life. In the absence of sufficient physical activity, physiology over time is gradually deteriorating toward the production of a lifestyle disease. Here, the ageing process, interacting with individual physiological heterogeneity, probably determines the age of presentation of a disease as well as the order of presentation of subsequent diseases. In this article, we discuss this hypothesis and related concepts in the context of the trajectory of healthy and non-healthy human ageing.

Resveratrol and Quercetin Potentiate the Cell Protection and Rescue Effects of NAD+ Precursors in HEK293 Cells Challenged by DNA Damaging Agent, N-Methyl-N′-nitro-N-nitrosoguanidine

DNA damage plays an essential role in the human ageing process. Recently, accumulating evidence has demonstrated that a decreased level of nicotinamide adenine dinucleotide (NAD+) is involved in human ageing and suggested that the natural supplements of NAD+ precursors and its homeostasis regulators might serve as a promising modality to slow down the human ageing process. In the present study, we analyzed the combinational effects and potential mechanism of NAD+ precursors, nicotinic acid (NA) and nicotinamide (NM), and the NAD+’ homeostasis regulators, resveratrol (R), and quercetin (Q) in the protection and rescue of HEK293 cells from N-methyl- N'-nitro- N nitrosoguanidine (MNNG)-induced DNA damage. The results indicate that resveratrol and quercetin can significantly potentiate the cell protection and rescue effects of NAD+ precursors in HEK293 cells attacked by the DNA damaging agent, MNNG. Intracellular NAD+ homeostasis and the PARP1 activation status are the key factors in determining the fate of the cells under DNA damaging stress.

Impact of COVID-19 on the signs of human ageing

The symptoms of post-COVID-19 syndrome (PPCS) are nonspecific and similar to those signs of aging. Therefore, it was suggested that those who have recovered from COVID-19 have accelerating the aging of the body. The aim of this work was to assess the influence of COVID-19 on the frequency of signs of aging. To collect the data, there was used a developed questionnaire, which included 17 signs of aging. There were received the answers from 306 people at the age from 30 to 70 years old. Among them, 98 people have had COVID-19. The average age of the people in the post-COVID-19 and COVID-19-free groups was 51,3 ± 1,65 and 50,4 ± 1,17, respectively (p> 0,05). The frequency of 14 signs of aging was significantly (p <0,01) higher among post-COVID-19 people. Particularly significant differences between post-COVID-19 and COVID-19-free were in the group of people under the age of 50 years old. The data, received by us, allowed to develop a computational procedure for diagnosing of PPCS. The task of attributing of the surveyed people to the post-COVID-19 and COVID-19-free group in accordance with the presence of certain symptoms was solved with the help of the Bayesian method in Gubler's modification, multiple logistic regression and neural network analysis. The developed diagnostic procedures can be used for the identification of the people with a high probability of the developing of PPCS. Keywords: rate of aging, post-COVID-19 syndrome, questionnaire

Oxygen Dependence of Flight Performance in Ageing Drosophila melanogaster

Similar to humans, insects lose their physical and physiological capacities with age, which makes them a convenient study system for human ageing. Although insects have an efficient oxygen-transport system, we know little about how their flight capacity changes with age and environmental oxygen conditions. We measured two types of locomotor performance in ageing Drosophila melanogaster flies: the frequency of wing beats and the capacity to climb vertical surfaces. Flight performance was measured under normoxia and hypoxia. As anticipated, ageing flies showed systematic deterioration of climbing performance, and low oxygen impeded flight performance. Against predictions, flight performance did not deteriorate with age, and younger and older flies showed similar levels of tolerance to low oxygen during flight. We suggest that among different insect locomotory activities, flight performance deteriorates slowly with age, which is surprising, given that insect flight is one of the most energy-demanding activities in animals. Apparently, the superior capacity of insects to rapidly deliver oxygen to flight muscles remains little altered by ageing, but we showed that insects can become oxygen limited in habitats with a poor oxygen supply (e.g., those at high elevations) during highly oxygen-demanding activities such as flight.

Age-related ceRNA networks and the mRNA/protein correlation in Drosophila ageing

Background As Drosophila is a classic model organism, understanding of the regulatory networks has great significance in revealing the genetic mechanisms of ageing and human diseases. Competing endogenous RNA (ceRNA)-mediated regulation is an important mechanism of circular RNA (circRNA) and long non-coding RNA (lncRNA) regulation in ageing and age-related disease. However, extensive analyses of the multi-omics (circRNA/miRNA/mRNA, lncRNA/miRNA/mRNA, and mRNA/protein) characteristics of adult Drosophila ageing have not been reported. Our results determine the ceRNA networks and the mRNA/protein correlations of key differentially expressed genes in adult Drosophila aging, and provide a solid foundation for understanding mechanisms of human ageing and ageing-related diseases. Results Here, differentially expressed circRNAs and microRNAs (miRNAs) between 7 and 42 day old Drosophila were screened and identified. Then, the differentially expressed mRNAs, circRNAs, miRNAs, lncRNAs, and proteins between day 7 and day 42 were used to analyse fly age-related circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks and the mRNA/protein correlation in Drosophila ageing. Several key ceRNA networks were identified, such as the circ_0006913/miR-985-3p/Abl, circ_0009500/miR-14-5p/SERCA, XLOC_100429/miR-14-5p/SERCA, and XLOC_100429/miR-14-5p/Vha100-4 networks. Subsequently, 16 pairs of differentially expressed interacting mRNAs/proteins were found, including 10 pairs with the same expression trends and 6 pairs with the opposite expression trends. Furthermore, real-time quantitative PCR (qPCR) was used to verify the expression level of those genes. Conclusions The discovery of these ceRNA networks and the mRNA/protein correlations in adult Drosophila ageing will provide new information for research on human ageing and age-related disease.