[{"command":"openDialog","selector":"#drupal-modal","settings":null,"data":"\u003Cdiv id=\u0022republish_modal_form\u0022\u003E\u003Cform class=\u0022modal-form-example-modal-form ecl-form\u0022 data-drupal-selector=\u0022modal-form-example-modal-form\u0022 action=\u0022\/en\/article\/modal\/9387\u0022 method=\u0022post\u0022 id=\u0022modal-form-example-modal-form\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cp\u003EHorizon articles can be republished for free under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.\u003C\/p\u003E\n \u003Cp\u003EYou must give appropriate credit. We ask you to do this by:\u003Cbr \/\u003E\n 1) Using the original journalist\u0027s byline\u003Cbr \/\u003E\n 2) Linking back to our original story\u003Cbr \/\u003E\n 3) Using the following text in the footer: This article was originally published in \u003Ca href=\u0027#\u0027\u003EHorizon, the EU Research and Innovation magazine\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003ESee our full republication guidelines \u003Ca href=\u0027\/horizon-magazine\/republish-our-stories\u0027\u003Ehere\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003EHTML for this article, including the attribution and page view counter, is below:\u003C\/p\u003E\u003Cdiv class=\u0022js-form-item form-item js-form-type-textarea form-item-body-content js-form-item-body-content ecl-form-group ecl-form-group--text-area form-no-label ecl-u-mv-m\u0022\u003E\n \n\u003Cdiv\u003E\n \u003Ctextarea data-drupal-selector=\u0022edit-body-content\u0022 aria-describedby=\u0022edit-body-content--description\u0022 id=\u0022edit-body-content\u0022 name=\u0022body_content\u0022 rows=\u00225\u0022 cols=\u002260\u0022 class=\u0022form-textarea ecl-text-area\u0022\u003E\u003Ch2\u003ECellular spring cleaning may keep us youthful and healthy for longer\u003C\/h2\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\n\n\u003Cp\u003EBy intervening in the processes that make our bodies and brains malfunction as we get older, can we delay the onset of age-related disorders, or even stop them developing entirely?\u003C\/p\u003E\n\n\u003Cp\u003EThe mythical fountain of youth has been a popular legend for thousands of years. The question of whether we can drink from its waters has\u0026nbsp;been nagging modern researchers working in the field of biological ageing (known as senescence) since 1889, when French doctor Charles-\u00c9douard Brown-S\u00e9quard injected himself with extracts from animal testicles. Following this, he claimed his mental and physical condition improved.\u003C\/p\u003E\n\n\u003Cp\u003EAlmost 150 years on, age-related disorders like Alzheimer\u2019s and heart disease have reached epidemic levels in the Global North, and the quest for rejuvenation has lost none of its appeal.\u003C\/p\u003E\n\n\u003Cp\u003EUnsurprisingly, rising life expectancy is largely to blame for this surge in disease. People born in Europe today can expect to live until they are aged 81.3 \u2013 a good 35 years longer than those entering the world in the late 19th century \u2013 however, medics agree that \u003Ca href=\u0022https:\/\/www.who.int\/data\/gho\/data\/themes\/mortality-and-global-health-estimates\/ghe-life-expectancy-and-healthy-life-expectancy\u0022\u003Equality of life in old age has not kept pace with longevity\u003C\/a\u003E. Many of us spend our elderly years - sometimes decades - living with mental or physical conditions caused almost entirely by the ageing process.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EOur aim needs to shift from staying alive for longer to achieving a better quality of life in old age.\r\n\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Nektarios Tavernarakis, bioscientist at the University of Crete in Greece\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\n\n\u003Cp\u003EOften there are no treatments for the conditions of old age, and the symptoms can be \u2018highly debilitating \u2013 sometimes devastating,\u2019 according to \u003Ca href=\u0022https:\/\/erc.europa.eu\/erc_member\/nektarios-tavernarakis\u0022\u003EProfessor Nektarios Tavernarakis\u003C\/a\u003E, a bioscientist at the University of Crete in Greece who studies ageing, cell death and neurodegeneration.\u003C\/p\u003E\n\n\u003Cp\u003E\u2018Our aim needs to shift from staying alive for longer to achieving a better quality of life in old age,\u2019 said Prof. Tavernarakis, who is also principle coordinator of the EU-funded \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/695190\u0022\u003EMANNA\u003C\/a\u003E project.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003ECell detox\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EProf. Tavernarakis and his colleagues are intent on understanding \u2013 and ultimately fixing \u2013 the cellular causes of biological decline. The benefits of extending a person\u2019s healthy years will be felt by society at large. Poor health in old-age poses a huge and growing burden on our social and healthcare systems. Alzheimer\u2019s disease alone \u003Ca href=\u0022https:\/\/institutducerveau-icm.org\/en\/key-figures\/#:~:text=to%20be%20discovered!-,NEURODEGENERATIVE%20DISEASES,cost%20of%20diseases%20in%20Europe.\u0022\u003Eaffects more than 4.9 million people in Europe\u003C\/a\u003E, and diseases and disorders of the nervous system and brain bring an annual cost of around \u20ac800 billion to Europe, according to 2010 figures.\u003C\/p\u003E\n\n\u003Cp\u003EThe question is, how can scientists hope to solve the problem of physiological decline when there is such a smorgasbord of seemingly unrelated disorders vying for their attention? From cancers to diseases that affect the internal organs, circulatory system and nervous system, there are many conditions associated with ageing.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EEssential housekeeping\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EMany are pinning their hopes on a biological process known as autophagy (meaning \u2018self-eating\u2019 in Greek). All cells use autophagy to rid themselves of toxic material (mostly unnecessary or damaged components). As we age, this essential housekeeping task is performed less efficiently leading to the buildup of errors and glitches that trigger disease-causing inflammation and ultimately necrotic cell death (known as necrosis).\u003C\/p\u003E\n\n\u003Cp\u003EThere is growing evidence that faulty autophagy is a common denominator in many of the disorders linked to old age. Necrosis contributes to incidence of tumours, liver disease, stroke, heart disease, and age-associated neurodegenerative disorders such as Alzheimer\u2019s and Parkinson\u2019s.\u003C\/p\u003E\n\n\u003Cp\u003EStudies in this area are in their infancy, but a burgeoning body of research suggests that boosting autophagy can extend cell survival and improve our prospects of good health.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EIf we could target those underlying processes of ageing, we might be able to slow down age-related degeneration and keep people healthier for longer.\r\n\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Linda Partridge, founding director of the Max Planck Institute for Biology of Ageing in Germany\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\n\n\u003Cp\u003ELooking to the future, Professor Linda Partridge, founding director of the Max Planck Institute for Biology of Ageing in Germany, said: \u2018We see the prospect of developing a single pill that will target the biological pathways that also involve autophagy. The idea would be to have a polypill that prevents the underlying mechanisms involved in more than one ageing-related condition.\u2019\u003C\/p\u003E\n\n\u003Cp\u003E\u2018If we could target those underlying processes of ageing, we might be able to slow down age-related degeneration and keep people healthier for longer. This would take us to a different place from where we are in now, where diseases are tackled one by one, as they arise.\u2019\u003C\/p\u003E\n\n\u003Cp\u003EProf. Partridge is the lead researcher of \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/741989\u0022\u003EGeroProtect\u003C\/a\u003E, an EU-funded project that sets out to find suitable drug candidate for such a \u2018geroprotective\u2019 polypill. \u2018We\u2019re not looking to increase lifespan, but to solve the problem of the ever-growing period of ill-health at the end of life,\u2019 she said.\u003C\/p\u003E\n\n\u003Cp\u003EProf. Tavernarakis\u0027 MANNA is focused on unpacking the link between autophagy and age-related degeneration of the nervous system. Much of the group\u2019s work is carried out on the worm \u003Cem\u003ECaenorhabditis elegans\u003C\/em\u003E, which, perhaps surprisingly, has a nervous system that\u2019s remarkably similar to that of humans.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EThrough our work on both C. elegans and human brain tissue, we can confirm that mitophagy is downregulated in Alzheimer\u2019s patients.\r\n\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Nektarios Tavernarakis, bioscientist at the University of Crete in Greece\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\n\n\u003Cp\u003EDuring the first four years of this project, the team has uncovered some of the key genes and molecular players involved in nerve-cell necrosis. Their work confirms that the survival and long-term maintenance of neurons is dependent on a sub-type of autophagy called mitophagy.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EToxic build-up\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EIn its prime, an organism uses mitophagy to eliminate old or toxic mitochondria (these are the organelles used by a cell to convert glucose \u2013 or simple sugar \u2013 into useful energy). But as age sets in and mitophagy slows down, faulty mitochondria start to accumulate in nerve cells. This build-up is toxic, triggering an inflammatory response that leads to cell damage and death. It\u2019s this progressive loss of functional nerve cells that causes a neurodegenerative disease to emerge.\u003C\/p\u003E\n\n\u003Cp\u003E\u2018Through our work on both \u003Cem\u003EC. elegans\u003C\/em\u003E and human brain tissue, we can confirm that mitophagy is downregulated in Alzheimer\u2019s patients,\u2019 said Prof. Tavernarakis. He added that efforts to decipher the precise mechanisms involved in mitophagic failure are still unfolding, but he is confident that complex genetic therapies will eventually be available to replace gene sequences that promote necrosis with ones that support healthy autophagy well into old age. Such therapies, however, are many years off.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EEat less, live longer\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EOne known way to induce autophagy is through caloric restriction. In experiments spanning worms, flies, mice, chimps and humans, researchers have found that consuming less food, or restricting an organism\u2019s feeding hours within a given day, activates autophagy.\u003C\/p\u003E\n\n\u003Cp\u003EIn non-human species, dietary restriction has also been found to extend lifespan and reduce or delay the onset of age-related conditions. Depending on the species, the most promising results show\u0026nbsp;lifespan extensions of between 50 - 300%. There is tantalising evidence that dietary restriction has positive impacts on the ageing of primates too, though the effects in humans remain controversial.\u003C\/p\u003E\n\n\u003Cp\u003EWhy might it help to go hungry? Quite simply, when the diet of an organism is restricted, its cells become deprived of glucose and begin to consume their own redundant material to generate energy. In other words, to sustain themselves, cells are forced into a detoxifying state of autophagy.\u003C\/p\u003E\n\n\u003Cp\u003E\u003Cstrong\u003EDisease prevention\u003C\/strong\u003E\u003C\/p\u003E\n\n\u003Cp\u003EThe problem with dietary restrictions is that generally people don\u2019t like them, and any attempt to reduce food intake tends to be short-term in humans. So, when it comes to enhancing autophagy, pharmaceutical interventions are a far more realistic prospect (though Prof. Partridge stresses that over-activating autophagy can also be problematic, as this can lead to cells destroying their contents at unfavourably high rates).\u003C\/p\u003E\n\n\u003Cp\u003EA number of promising drug candidates have already been identified. Most notable are Urolithin A (produced by certain gut bacteria after they\u2019ve been fed with ellagitannins, which are found in pomegranates, strawberries, raspberries and walnuts) and rapamycin (a natural antifungal produced by soil bacteria).\u003C\/p\u003E\n\n\u003Cp\u003EThese two compounds are known to be involved in the upregulation of autophagy. In mice, worms and fruitflies, they have also been found to extend lifespan. Shortly, the geroprotective properties of these compounds will be put to the test in human clinical trials.\u003C\/p\u003E\n\n\u003Cp\u003EProf. Partridge \u2013 who has been studying the underlying mechanisms that make rapamycin effective in boosting autophagy in animal models \u2013 is hopeful that the results of human trials will take her team closer to developing their game-changing polypill.\u003C\/p\u003E\n\n\u003Cp\u003E\u2018Eventually we may end up with a drug that is taken very much like people today take statins (for cholesterol) or pills to lower blood pressure,\u2019 she said. \u2018Medicines that are taken over a very long period of time to prevent ill-health long before disease has even occurred.\u2019\u003C\/p\u003E\n\n\u003Ch5\u003EThe research in this article was funded by the EU. 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