Given the competing roles described above

Given the competing roles described above, an important question is whether treatment of cancer by autophagy inhibition will lead to neurodegenerative side effects and likewise, that treatment of neurodegenerative diseases with autophagy promoting agents might promote pre-malignant tumors. There are currently no studies that specifically induce autophagy, making it difficult to address the risk of autophagy inducing agents. However, because activities like exercise and caloric restriction that induce autophagy systemically (He et al., 2012; Pietrocola et al., 2016) are known for their health advantages, we speculate that specific autophagy induction may be safe. We must also consider the role of autophagy manipulation intended to treat one disease on other systems and organs, such as the liver (Madrigal-Matute and Cuervo, 2016).
Concluding Remarks
Introduction The ageing global ache inhibitor represents one of the greatest challenges to modern society. Ageing is the biggest risk factor for some of the most debilitating and distressing diseases known, including neurodegenerative diseases such as Parkinson\'s and Alzheimer\'s, as well as cardiovascular, inflammatory and metabolic disease, as well as cancer. Collectively, the diseases of ageing represent the biggest causes of morbidity and mortality in the developed world (Kennedy and Pennypacker, 2014). While the study and treatment of these diseases in isolation has yielded a great deal of knowledge and a significant improvement in patient quality of life, it is important to acknowledge that these diseases do not exist in isolation. An aged individual may possess any number of co-morbidities, each of which can exponentially complicate any required therapeutic interventions. Given the complexity of treating age-related co-morbidities separately, the idea of targeting ageing itself as a means of reversing the pathogenesis of several diseases at once is appealing (Faragher et al., 2009). This review will evaluate current developments in translating basic ageing research into useful therapeutics. Particular attention will be paid to ongoing attempts to repurpose already available drugs, before touching on promising drugs that, based on recent evidence in pre-clinical models, could also be repurposed. Additionally, new therapeutics being developed specifically to target ageing are discussed. Finally, since any appraisal of anti-ageing function will only be possible with robust biomarkers of ageing (Kenessary et al., 2013), we present a brief review of the search for powerful predictors of physiological age. To highlight strategies with greatest potential to manipulate human ageing, only drugs that have demonstrable effects in mammals will be considered. Other reviews have covered longevity-enhancing treatments in non-mammalian models (Vaiserman and Marotta, 2016; Vaiserman et al., 2016).
Ageing as a Clinical Indication Twenty years ago, the eminent epidemiologist Richard Doll argued that ageing as a single unified phenomenon did not exist (Peto and Doll, 1997). Doll proposed that, on the balance of evidence available at the time, it was better to consider each of the apparently independent diseases of ageing as separate in nature and thus separate in possible treatments. Current advances in gerontology have since shown that many age-related diseases do indeed share common causes and thus may be reversed or prevented through common cures. Since then the shift in scientific consensus from regarding ageing as an inexorable, entropic process to one that is mediated by well-defined - and importantly, malleable - biochemical pathways has been dramatic. Initial studies in nematodes demonstrated genetic manipulation of longevity was possible (Kenyon et al., 1993). Subsequent studies are just beginning to tease out the many genetic determinants of human longevity (Zhang et al., 2016). Briefly, ageing is thought to be caused by developmental processes that evolved to ensure successful reproductive maturation but carry on long after reproductive maturity is reached (antagonistic pleiotropy; Williams, 1957), resulting in molecular and physiological defects that render organisms frail and less able to respond to stress. These molecular and physiological defects manifest in many forms over several hierarchical layers of molecular, cellular and tissue biology. Cells within old individuals may possess aggregated proteins, dysfunctional mitochondria, (epi)genetic lesions and eroded telomeres. This can lead to senescence and subsequent depletion of active stem cell populations, impairing regenerative capacity and further promoting tissue ageing. Systemically, age-related immunodegeneration, disrupted circadian rhythms, impaired nutrient sensing and improper autocrine and paracrine signalling processes combine to promote an “aged” extracellular environment, causing or exacerbating organ failure and leading to the exponential increase in morbidity and mortality that characterises an ageing population (reviewed by López-Otín et al., 2013; Kirkwood, 2005; summarised in Fig. 1).