The cnidarian Hydra polyps escape senescence over the years, most likely as a result of the robust activity of their three stem cell populations, which continuously self-renew in the body column and differentiate at the extremities following a tightly coordinated spatial pattern. However Paul Brien showed in 1953 that Hydra oligactis polyps undergo rapid aging and death when they become sexually differentiated upon cold exposure. The features of this inducible aging phenotype are reviewed here, namely the cellular alterations detected after several weeks, as the decreasing density in somatic interstitial cell derivatives, the disorganization of the apical nervous system, the disorganization of the myofibers in the epithelial cells. As a consequence tissue replacement normally observed to maintain homeostasis, feeding behavior, and contractility of the animal are dramatically affected. Interestingly this aging phenotype is not expresses by all H.o strains, which thus provide a powerful experimental model for investigating the genetic control of low senescence and aging. Given the presence in cnidarians of a large collection of human orthologs that were lost in ecdysozoans, such approaches might help uncover novel regulators of aging in vertebrates.

Epithelial sheets, a synapomorphy of all metazoans but porifers, are present as 2 layers in cnidarians, ectoderm and endoderm, joined at their basal side by an extra-cellular matrix named mesoglea. In the Hydra polyp, epithelial cells of the body column are unipotent stem cells that continuously self-renew and concomitantly express their epitheliomuscular features. These multifunctional contractile cells maintain homeostasis by providing a protective physical barrier, by digesting nutrients, by selecting a stable microbiota, and by rapidly closing wounds. In addition, epithelial cells are highly plastic, supporting the adaptation of Hydra to physiological and environmental changes, such as long starvation periods where survival relies on a highly dynamic autophagy flux. Epithelial cells also play key roles in developmental processes as evidenced by the organizer activity they develop to promote budding and regeneration. We propose here an integrative view of the homeostatic and developmental aspects of epithelial plasticity in Hydra.

Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris. However sexual animals from the H. oligactis cold-sensitive (Ho_CS) strain develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within three months. This phenotype is not observed in the cold-resistant Ho_CR strain. To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it irreversibly reduced in aging Ho_CS while sustained in non-aging Ho_CR. We also identified a deficient autophagy in Ho_CS epithelial cells, with a constitutive deficiency in autophagosome formation as detected with the mCherry-eGFP-LC3A/B autophagy sensor, an inefficient response to starvation as evidenced by the accumulation of the autophagosome cargo protein p62/SQSTM1, and a poorly-inducible autophagy flux upon proteasome inhibition. In the non-aging H. vulgaris animals, the blockade of autophagy by knocking-down WIPI2 suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.

Purpose Assess the individual and combined diagnostic value of amyloid-PET and tau-PET in a memory clinic population. Methods Clinical reports of 136 patients were randomly assigned to two diagnostic pathways: AMY-TAU, amyloid-PET is presented before tau-PET; and TAU-AMY, tau-PET is presented before amyloid-PET. Two neurologists independently assessed all reports with a balanced randomized design, and expressed etiological diagnosis and diagnostic confidence (50–100%) three times: (i) at baseline based on the routine diagnostic workup, (ii) after the first exam (amyloid-PET for the AMY-TAU pathway, and tau-PET for the TAU-AMY pathway), and (iii) after the remaining exam. The main outcomes were changes in diagnosis (from AD to non-AD or vice versa) and in diagnostic confidence. Results Amyloid-PET and tau-PET, when presented as the first exam, resulted in a change of etiological diagnosis in 28% (p = 0.006) and 28% (p < 0.001) of cases, and diagnostic confidence increased by 18% (p < 0.001) and 19% (p < 0.001) respectively, with no differences between exams (p > 0.05). We observed a stronger impact of a negative amyloid-PET versus a negative tau-PET (p = 0.014). When added as the second exam, amyloid-PET and tau-PET resulted in a further change in etiological diagnosis in 6% (p = 0.077) and 9% (p = 0.149) of cases, and diagnostic confidence increased by 4% (p < 0.001) and 5% (p < 0.001) respectively, with no differences between exams (p > 0.05). Conclusion Amyloid-PET and tau-PET significantly impacted diagnosis and diagnostic confidence in a similar way, although a negative amyloid-PET has a stronger impact on diagnosis than a negative tau-PET. Adding either of the two as second exam further improved diagnostic confidence. Trial number PB 2016-01346.

Background Subjective cognitive decline (SCD) is the subjective perception of a decline in memory and/or other cognitive functions in the absence of objective evidence. Some SCD individuals however may suffer from very early stages of neurodegenerative diseases (such as Alzheimer’s disease, AD), minor psychiatric conditions, neurological, and/or somatic comorbidities. Even if a theoretical framework has been established, the etiology of SCD remains far from elucidated. Clinical observations recently lead to the hypothesis that individuals with incipient AD may have overestimated metacognitive judgements of their own cognitive performance, while those with psychiatric disorders typically present underestimated metacognitive judgements. Moreover, brain connectivity changes are known correlates of AD and psychiatric conditions and might be used as biomarkers to discriminate SCD individuals of different etiologies. The aim of the COSCODE study is to identify metacognition, connectivity, behavioral, and biomarker profiles associated with different etiologies of SCD. Here we present its rationale and study design. Methods COSCODE is an observational, longitudinal (4 years), prospective clinical cohort study involving 120 SCD, and 80 control study participants (40 individuals with no cognitive impairment, and 40 living with mild cognitive impairment - MCI, or dementia due to AD), all of which will undergo diffusion magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) as well as behavioral and biomarker assessments at baseline and after 1 and 2 years. Both hypothesis-driven and data-driven cluster analysis approaches will be used to identify SCD sub-types based on metacognition, connectivity, behavioral, and biomarker features. Conclusion COSCODE will allow defining and interpreting the constellation of signs and symptoms associated with different etiologies of SCD, paving the way to the development of cost-effective risk assessment and prevention protocols.