The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.

mTOR Signaling in Growth, Metabolism, and Disease

With the unprecedented surge in geriatric populations, public health policies should prioritize plans for ensuring independence and dignity of elders. Demographic transformations have social, political, and economic implications that influence funding and provisioning geriatric care. While maximum life span is genetically determined, East Asia has shown the fastest improvements in life expectancy at birth, increasing from 45 years (1950) to 74 years (2005). 65-year olds would increase from 12.5% to 20% in the USA by 2030, while China and India would encounter larger numbers. Health promotion schemes and health care management strategies have propelled an abrupt rise in the survival rates of elders, accompanied by the increasing need for trained personnel, specialized care, and budgetary policies to earmark funds from young taxpayers to pay for geriatric care. “Compression of morbidity” hypothesis optimistically proposes that age-related disease and disability can be postponed to terminal years of life. Education, supportive technologies, and treatments improve the quality of life of elderly citizens in developed industrialized societies, but the obesity epidemic is a looming threat. Bioethicists warn that rising geriatric populations demand detailed plans to avert bankruptcy of insurance companies. It is important to understand that the infirmity of old age is, at least partly, the inevitable outcome of D. G. T. Parambi College of Pharmacy, Department of Pharmaceutical Chemistry, Jouf University, Sakaka, Al Jouf, Saudi Arabia M. K. Unnikrishnan · A. Marathakam Department of Pharmaceutical Chemistry, National College of Pharmacy, Calicut, Kerala, India B. Mathew (*) Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, Kerala, India # Springer Nature Singapore Pte Ltd. 2020 S. M. Nabavi et al. (eds.), Nutrients and Nutraceuticals for Active & Healthy Ageing, https://doi.org/10.1007/978-981-15-3552-9_1 1 deleterious mutations accumulating in post-reproductive life. Reproductive success being key to survival, harmful mutations that express in early reproductive period of life are selectively deleted, while deleterious mutations expressing in post-reproductive life would accumulate. Antagonistic pleiotropy proposes that genes serving a favorable outcome in early life would accumulate, even if harmful in later life, leading to senescence. Genes promoting inflammatory repair in early life have been implicated in chronic inflammatory diseases of old age. Public health policies, especially in lifestyle disorders, can learn from evolutionary biology, but such research is scanty. While global mortality rates have plummeted towards the end of the twentieth century, death rates from Alzheimer’s disease, heart disease, cerebrovascular disease, influenza, and pneumonia registered exponential increases with age. Most common chronic conditions among elderly Americans are hypertension, coronary heart diseases, chronic joint symptoms, and stroke. Patterns in comorbidity-co-occurrence of chronic conditions help assess disease burden and prevalence. Hypertension, cholesterol, sedentary life, obesity, and smoking have been associated with mortality from CHD, cancer, and stroke. Lung, colon, prostate, bladder, and rectum cancers show the highest incidence in men, whereas breast, uterine, colon, rectum, and lung cancers are the highest in women. An OECD report suggests that dementia affects 30% of those aged 85–89. Epidemiological data on “functional impairment” or “disability,” reveal that greater understanding of the occurrence, causes, and consequences of disability help formulate preventive therapies for minimizing disability. Metrics of disability can be a powerful tool for estimating adverse reactions, presence and severity of multiple pathogeneses, including physical, cognitive, and psychological, as well as their potential synergistic effects. Activities of daily living (ADL), instrumental activities of daily living (IADL), and objective assessment of physical performance help assess capacity for independent community life, an essential aspect of long-term geriatric care.

Nutrients and Nutraceuticals for Active & Healthy Ageing

Abstract Background Cancer is considered one of the primary illnesses that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. As most of the target-specific anticancer drugs failed to achieve the expected result so far, new multi-targeted therapies using natural products have become significant. Natural products are readily applicable, inexpensive, accessible and acceptable therapeutic approaches with minimum cytotoxicity. This review explores the relationship between dietary factors and the probability of development of gastric cancer. Over the years, it has been proven that there are many natural products that have chemo-preventative effects such as vitamins, probiotics and prebiotics, green tea, and resveratrol on gastric cancer. Many investigations have looked into the links between dietary components and the risk of stomach cancer and a variety of protective and deleterious factors have been identified in our diet that is associated with gastric cancer. In this study, we have summarized the preventive and injurious components that affect the incidence of gastric cancer. Conclusion Based on the potential of natural products for the discovery of new compounds for the treatment of diseases, the purpose of the present review was to investigate the importance of dietary products mitigating the impacts due to the development of gastric cancer. The current analysis proves the protective as well as harmful roles of many elements which are found in our diet in the development of gastric cancer. Our findings can have significant public health implications in terms of gastric cancer prevention. There is an inherent need to offer an insight into benefits and risks, clinical trial designs future translational and cohort studies before effectively clinically translated. 

/pdf/dietary-factors-associated-with-gastric-cancer-a-review-rm06gs2y.pdf

Dietary factors associated with gastric cancer - a review

The prolongation of lifespan is a desired condition, strictly depending from several factors, including genetics and environmental factors. In this context, nutrition can be a powerful tool, useful to modulate ageing. In particular, polyphenols constituents, widely distributed in edible vegetables and fruits, can act on specific intracellular markers, among which the enzyme sirtuin-1 (SIRT1) and several kinases, mainly AMPK, mTOR and MAPK/ERK and then contribute to reduce proinflammatory and fibrotic processes typical of the ageing; therefore inhibiting the progression of age-related pathologies, including neurodegenerative, cardiovascular and cancer. Indeed polyphenol family is very big and includes numerous subgroups of chemical constituents, ranging from rather elementary substances, such as phenolic acids and stilbenes, to complex polymerized molecules, such as tannins. They are different for distribution in the natural king and for bio-pharmacological profile. In this chapter the role played from polyphenols in the senescence has been evaluated.

Dietary Polyphenols for Active and Healthy Ageing

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Dietary Polyphenols for Active and Healthy Ageing