Introduction
Due to all the advancements in medicine, hygiene and agriculture over the last 100 years humans are living far longer, especially in developed countries. Living for longer brings problems of its own. Ageing is described as “a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death” 1. As the human body ages, it naturally deteriorates by primary ageing but also becomes more susceptible to many diseases including cancer, diabetes, cardiovascular diseases (e.g. atherosclerosis) and neurodegenerative disease (including Alzheimer’s and Huntington’s) due to secondary ageing. Modern medicine still doesn’t have a way of combating most of these diseases and developing drugs to combat each individually is an extremely expensive and time-consuming process. It would be revolutionary if we could find something that could reduce the risk of contracting these diseases or help in recovery.
A paper published by McCal et al. in 1935 (2) gave preliminary evidence that controlling diet to reduce calorie intake has a profound effect on lifespan. Experimentation has been carried out on a wide range of species: from Drosophila to rats, the results all seem to point to the fact that periods of fasting are beneficial for health and longevity of individuals. Research since this paper has explored a number of areas, including the effect of fasting on the incidence of ageing related diseases, its effect on lengthening lifespan, the biochemical basis of what happens when an organism is starved for a period of time and how this can improve their health. Fasting appears to have an effect on both primary ageing as it increases the maximal lifespan and secondary ageing due to an observed increase in average lifespan of a population 2. The following review will cover these topics, as well as exploring evidence against the beneficial nature of fasting and how other lifestyle changes could bring about the same effects.
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Primary Ageing
Primary ageing occurs as part of a natural decline in which several cellular processes become impaired or altered as a result of underlying, time-accumulated damage to proteins or DNA. The hallmarks of ageing can be categorised into the primary hallmarks, antagonistic hallmarks and integrative hallmarks1. Primary hallmarks include genome instability, telomere shortening, epigenetic alterations and impaired proteostasis. These hallmarks are always detrimental to the organism and can lead to pathologies and disease1.
Antagonistic hallmarks occur as a result of the primary hallmarks, these are altered nutrient sensing, damaged mitochondria which can lead to the production of reactive oxygen species (ROS) and cellular senescence1. In the case of antagonistic hallmarks, low levels can help ameliorate the ageing process. For example, alterations in the insulin-like growth factor (IGF) and insulin signalling pathway have been linked to the retardation of the ageing process3. This will be discussed further in Section 3c. Integrative hallmarks include stem cell exhaustion and changed intercellular communication. These hallmarks directly affect tissues and result in the phenotype of ageing1.
As these hallmarks often influence each other, targeting one cause of ageing could have beneficial effects on the other factors to overall slow-down the ageing process and extend lifespan.
Secondary Ageing
Secondary ageing encompasses the diseases associated with old age4 and as such is much more dependent on environmental factors and the lifestyle an individual leads. Many diseases are associated with ageing, in particular neurodegenerative diseases like Alzheimer’s and Huntington’s disease. In Alzheimer’s disease, toxic plaques of -amyloid peptide (A)5. Issues arise when the plaques are not cleared, this is a more common problem in older individuals as their proteostasis machinery is not as effective as it used to be. Little is understood about how this causes Alzheimer’s and so developing drugs to treat and cure Alzheimer’s is proving difficult. At the moment, treatments only exist to treat the symptoms of Alzheimer’s rather than actually curing the disease6.
Another disease that is commonly associated with ageing is cancer. Age is a cancer risk factor and cancer incidence increases with age7. The mechanisms that underlie aging and cancer are closely related1. In both there is genomic instability, shortening of telomeres and epigenetic changes3. If the processes that are altered in ageing could be controlled by changes to an individual’s lifestyle, this could result in longer lifespans and a decreased risk of carcinogenesis7.
Increased inflammation is a problem in ageing (“inflammaging”1) that manifests itself in a number of pathologies. Older individuals often experience increased systemic inflammation in response to lifelong stress from antigens.