Aging Biology最新文献

The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of Caenorhabditis elegans to highlight trends shared among individuals, we employed 16s rRNA gene sequencing, CFU counts and fluorescent imaging, identifying an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormaechei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its potential for exacerbating infection susceptibility. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ^+/-. The 3xTgAD/Polβ^+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ^+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

Stochastic effects are central to the biology and demography of aging. Genetically identical individuals do not all die at the exact same time but show a distribution of lifespan. Although such effects are appreciated, any cascading effects from the stochastic effects of aging are underappreciated. We show here that genetically identical female flies (Drosophila melanogaster) that live long produce longer-lived daughters. In line with previous work, we also find that daughters born to older mothers are shorter-lived, also termed the Lansing effect. We further show that longer-lived flies produce less offspring, suggesting an apparent trade-off due to stochastic effects alone. We explain these effects using an extension of the reliability theory of aging by dichotomizing aging physiology in reproduction and lifespan-supporting units. These simple models reproduce the nongenetic inheritance of lifespan, the Lansing effect, and trade-offs between reproduction and lifespan. Our work implies that if nongenetic inheritance of lifespan is widespread, it explains the generally low heritability of this trait. Furthermore, trade-offs between performance, for example, reproduction, and lifespan may be less widespread than predicted by the evolutionary biology of aging, stemming from stochasticity rather than differential investment. Antiaging treatments could therefore come without any unintended costs to other physiology, a perceived risk that limits the translation of these treatments to humans.