Longevity

The Benefits Of Fasting: Part 2 – Slowing Ageing?

Posted on 27 November 2020

In last week’s article, we explored the most immediate benefit of fasting – weight loss – and why fasting may be more effective than other weight loss strategies. In that article, we hinted that the effects of fasting on pathways like insulin signalling could have more profound health benefits than simply helping you to burn fat. In this article, we will explore perhaps the most enticing and intriguing of these benefits – the possibility that fasting could slow the rate at which you age.

Metformin: First pill that purportedly treats age-related illnesses in  review for approval for trials | Genetic Literacy Project

What Would It Mean To Slow Ageing?

Before we begin, we need to be clear on what would actually constitute a true slowing of the ageing process. Over the past century, average human lifespan has greatly increased, but this is simply because we are far less likely to die before we reach our maximum lifespan. In fact, there is no evidence to suggest that the maximum age to which a human can live has increased over the last hundred or even the last thousand years. Throughout our lives, our tissues, our cells and our DNA accumulate damage. Part of this damage is influenced by the environment, but much of it is inherent, and we will eventually succumb to it. This sets our maximum lifespan, and extending it is likely to require significant breakthroughs in biotechnology and longevity research.

Healthspan, on the other hand, refers to the period of life spent in good health, free of chronic diseases of ageing. Improvements in healthspan don’t necessarily translate into increased lifespan or vice versa, and this is exemplified by today’s ageing demographic. People are living longer with debilitating diseases than ever before, as modern medicine has become better at keeping people with chronic conditions alive than preventing those conditions from developing to begin with.

Modified from:
https://www.slideshare.net/GFHEU/confessions-from-a-doctor-from-the-21st-century-how-doctors-travelled-from-low-tech-to-high-tech-but-actually-might-consider-going-back-again-a-bit

If an intervention truly slowed the ageing process, we would expect maximum lifespan to increase. The inherent rate at which damage accumulates should be slowed, raising the ‘hard cap’ on human lifespan. We would also expect healthspan to improve, as we would hope that a reduced rate of damage would make an older person’s body biologically equivalent to that of a younger person.

Fasting In Animal Models

One of the reasons fasting could be seen as a path to slowing the ageing process is the promising evidence in animal models. Forms of dietary restriction such as intermittent fasting can dramatically increase the lifespan of C.elegans worms, fruit flies, mice and rats (by around 60 – 80% or even more), and also reduces their risk of developing age-related disease.

Genes to Genomes: a blog from the Genetics Society of America
C.elegans worms

Animal studies have also reported that biomarkers of ageing, such as shortened telomeres and dysfunctional mitochondria, can be reduced by fasting. This seems to suggest that fasting slows some of the fundamental processes that underlie ageing. Together with the reported lifespan-extending effects, many scientists now consider fasting (and calorie restriction in general) to be an intervention capable of slowing the ageing process in animals. The important question is of course: do these benefits hold true in humans? Well, we’ll get to that. First, though, let’s ask another important question: why does something as simple as the withdrawal of food lead to such dramatic effects on lifespan?

Fasting Slows Ageing At The Cellular and Molecular Level

Organisms can typically experience significant and sudden variations in the amount of nutrients available to them. In order to survive, living organisms need to be able respond to these variations, utilising and storing resources when they are plentiful, while conserving them when they are scarce. In order to do this, cells have evolved nutrient-sensing pathways – molecular messaging systems that control the activity of different genes based on how much energy is available.

These pathways are complex, but there are a few key molecules:

  • AMPK senses the amount of energy (in the form of ATP) that is present within the cell.
  • mTOR responds to the availability of nutrients (lipids, amino acids, glucose) and growth factors.
Deregulated Nutrient Sensing | Life Science Research | Merck

A low availability of nutrients, growth factors, and energy causes cells to shift their focus from growth to survival, getting rid of ‘junk’ and unnecessary components that can be rebuilt in a more functional way upon refeeding. The most significant anti-ageing effects include:

  • Reduced cellular senescence: Senescent cells are unable to divide, and can secrete harmful signalling molecules. The build-up of senescent cells within tissues is associated with most chronic diseases of ageing.
  • Reduced inflammation and oxidative stress: Ageing is characterised by an increase in background inflammation and the production of reactive oxygen species – metabolic by-products that damage other molecules.
  • Repair of damaged DNA: The accumulation of damage to DNA, including the telomeres, is thought to contribute to the ageing process.
  • Autophagy: Autophagy (literally self-eating) is the destruction and recycling of damaged cell components. Defective autophagy is associated with age – related disease.

Hopefully, you now have some understanding of how fasting can slow ageing at a molecular level. Perhaps you are considering fasting or calorie restriction as a means to age more slowly and live longer. Is it reasonable to expect fasting to have tangible anti-ageing effects in humans?

Does Fasting Slow Ageing In Humans?

Dietitian: Intermittent fasting not sustainable long term | Stuff.co.nz

Measuring whether fasting can affect human lifespan is not an easy task. Unlike in animal studies, we cannot make a group of humans fast under controlled conditions throughout their entire lives, and the high life expectancy of humans makes long term studies of fasting and lifespan impractical. This is compounded by the fact that the effects of fasting on lifespan are almost certainly more prominent in short-lived species.

We may not be able to perform controlled longitudinal studies of lifespan extension in humans, but we can study our close non-human relatives. Research in rhesus monkeys suggests significant increases in survival with calorie restriction (which, while not the same as fasting (see below) works through many of the same mechanisms), as well as reduced incidence of chronic diseases of ageing. However, some such studies have also found no effect on survival.

We can also study the lifespan and healthspan in populations with below average calorie intake without malnutrition. However, such populations are abnormal by their very nature, and tend to follow other practices associated with increased lifespan and healthspan. For example, the long lived population of Okinawa in Japan not only consume less food than average, but also consume healthier foods and exercise more. This makes it difficult to say whether increases in lifespan seen amongst such populations are actually due to the effects of dietary restriction.

Okinawa's Longevity Lessons - Blue Zones

While fasting and calorie restriction are both forms of dietary restriction that act through many of the same mechanisms, they are not the same thing and do not elicit the same metabolic responses. There are still unanswered questions about the relative benefits of these two dietary interventions, but a discussion on this will have to wait until a later article.

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One thing that can be said with confidence is that fasting can reduce risk factors for age related diseases in humans. These include insulin resistance, oxidative stress, inflammation, mitochondrial dysfunction and high blood pressure. Unfortunately, conclusive evidence for the effects of fasting on other important markers of ageing (like telomere shortening) is currently lacking, though that’s not to say that future studies won’t uncover benefits.


References

Influence of short-term repeated fasting on the longevity of female (NZB x NZW)F1 mice: DOI: 10.1016/s0047-6374(00)00109-3

Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans: https://doi.org/10.1038/nature07583

Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension: DOI: 10.1016/j.cub.2018.04.015

Effects of intermittent feeding upon growth and life span in rats: DOI: 10.1159/000212538

Downregulation of mTOR Signaling Increases Stem Cell Population Telomere Length during Starvation of Immortal Planarians: DOI: 10.1016/j.stemcr.2019.06.005

Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle: doi: 10.1371/journal.pone.0195912

Dietary Restriction, Growth Factors and Aging: from yeast to humans: doi: 10.1126/science.1172539

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