These authors contributed equally to this work.Keywords: autophagy, aging, a-synuclein, dopaminergic neuron loss, motor dysfunction, neurodegeneration, Parkinson's disease, SpermidineAs our society ages, neurodegenerative disorders like Parkinson`s disease (PD) are increasing in pandemic proportions. While mechanistic understanding of PD is advancing, a treatment with well tolerable drugs is still elusive. Here, we show that administration of the naturally occurring polyamine spermidine, which declines continuously during aging in various species, alleviates a series of PD-related degenerative processes in the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, two established model systems for PD pathology. In the fruit fly, simple feeding with spermidine inhibited loss of climbing activity and early organismal death upon heterologous expression of human a-synuclein, which is thought to be the principal toxic trigger of PD. In this line, administration of spermidine rescued a-synuclein-induced loss of dopaminergic neurons, a hallmark of PD, in nematodes. Alleviation of PD-related neurodegeneration by spermidine was accompanied by induction of autophagy, suggesting that this cytoprotective process may be responsible for the beneficial effects of spermidine administration.

Endocrine-disrupting chemicals (EDCs) are man-made chemicals that interfere with hormonal signalling pathways. They are used in, for example, production of common household materials, in resin-based medical supplies and in pesticides. Thus, they are environmentally ubiquitous and human beings and wildlife are exposed to them on a daily basis. Early-life exposure to EDCs has been associated with later-life adversities such as obesity, diabetes and cancer. Mechanisms underlying such associations are unknown but are likely to be mediated by epigenetic changes induced by EDCs. Epigenetics is the study of changes in gene function that are heritable but do not entail a change in DNA sequence. EDCs have been shown to affect epigenetic marks such as DNA methylation and histone modifications. The scope of this article was to review today's knowledge about mechanisms involved in EDC-induced epigenetic changes and to discuss how this knowledge could be used for designing novel methods addressing epigenetic effects of EDCs.Since the industrial revolution, there has been a constant release of chemicals into the environment, which is linked to the increase of various health problems. A group of such environmental chemicals are endocrine-disrupting chemicals (EDCs) that interfere with the hormonal system. EDCs include a wide range of chemicals such as drugs, pesticides, plastic softeners, flame retardants. Thus, human beings and wildlife are exposed to these compounds on a daily basis, and EDCs are detectable in various body fluids [1,2].Increasing evidence suggests that EDC exposure during early life, in particular during foetal development, contributes to a variety of later-life adversaries, from cancer to cognitive impairments [3][4][5]. For instance, the synthetic oestrogen diethylstilbestrol (DES), which was given to women in the 1940s-1970s during early pregnancy to prevent miscarriages, increased the risk of a rare vaginal clear cell adenocarcinoma and infertility in the daughters (DES daughters) [6,7]. And even in the second-generation, adverse effects of DES have been reported. For example, the sons of DES daughters have increased risk of hypospadias, an abnormality of the male reproductive system [8]. It is not fully clear how chemical exposure during early development leads to persistent changes that manifest as diseases much later in life, or even in the next generation. However, increasing evidence points towards a central role for epigenetic mechanisms in these long-lasting effects of EDCs and other chemicals. Epigenetic mechanisms are responsible for permanent transcriptional regulation, and epigenetic changes can be defined as 'any long-term change in gene function that persists even when the initial trigger is long gone and that does not involve a change in gene sequence or structure' [9]. In recent years, a wealth of experimental studies and some evidence from epidemiology have demonstrated that EDCs indeed induce epigenetic changes [10].There is increasing concern in society that developmental expo...