Ageing Deceleration

Globally, the average human life span has increased steadily over the past 30 years. However, our average health span – our years spent in good health – has not been able to keep pace, meaning that people are living longer in poor health.

In Australia, the average person can expect to live the remaining 13 years of their life in poor health which most commonly includes heart disease, stroke, neurological diseases, diabetes, and metabolic risks [33069327].

As we age, these health problems become more and more likely, so much so that aging is the greatest risk factor for chronic and debilitating disease.

Therefore, targeting aging processes provides the best opportunities for delaying disease and compressing morbidity.

By delaying disease we see an increase in health-span, life quality and productivity

By compressing morbidity we see a decrease in duration of frailty and the need for multiple medications to treat or prevent disease.

 

How do we target aging?

First, let’s explore what actually happens as we age:

Aging is best described as an increase in chronic disease and decrease in physical resilience.

The process commonly includes the following symptoms:

  • Increase in chronic inflammation, fibrosis, sarcopenia, and bone loss

  • Decrease in maintenance of tissue and organ systems

  • Decrease in capacity to repair damage

  • Accumulation in reactive oxygen species, misfolded proteins and glycated molecules

Eventually, the end of the process is marked by failure in one or more organ systems.

Figure 1: The 9 Hallmarks of aging 

The Hallmarks of Aging [23746838] leading to gradual deterioration of tissues and organs and other symptoms of aging are largely characterised by:

  • An ordered change to the epigenome and;

  • a gradual accumulation of random molecular defects in cells.

The epigenome is the layer between our genes and the environment which effectively switches certain genes ‘on’ and ‘off’ according to different environmental factors (e.g exercise, diet, pollutants, smoking).

You can think of this process much like a conductor guiding and orchestra. In this instance, a successful, harmonious performance relies on each instrument (the genes) being played properly and at the correct times by the musicians (the cells) under the direction of the conductor (epigenome).

As we age, our epigenome begins to falter and so that ability to efficiently regulate which genes are active or not starts to weaken and the ‘harmony’ is lost. This explains why our organs and tissues start to lose their functionality.

    Recent studies have shown that the rate of this epigenetic aging has a direct effect on our health, such that the faster the rate, the higher the risk for developing cardiovascular diseases and cancer [33632308] [35346416]. Conversely, environmental factors such as stress have also been shown to increase the rate of epigenetic aging [35113041].

    Now before you despair, let me tell you something really exciting. Not only have scientists discovered that the rate of epigenetic aging can be reduced with a high quality diet5 [34134146], there is growing evidence to suggest that it can even be reversed by as much as 2 years  [35390271] [31496122].

    This means that on the outside you may be 55 but on the inside, your body is only 53. Anyone that is experiencing aging can relate to how much difference a couple of years can make.

    When it comes to targeting aging, there are 5 key suspects we should focus on:

    • Senescent cells: these cells are both by-products and key drivers of the aging process. They are cells which have permanently stopped dividing and instead send out inflammatory and pro-aging S.O.S signals to other cells which intensifies the aging process. Removing senescent cells slows down aging, rejuvenates tissues and increases health span [30526770] [30395873].

    • Leaky mitochondria: when mitochondria become impaired during the aging process, they leak toxic oxidants which can damage DNA and produce senescent cells. Removing damaged mitochondria increases cell health and prevents senescence [34360946] [32308810].

    • Overactive mTor: mTor is a protein which combines signals from insulin, growth factors, nutrients, energy levels and oxygen and determines whether a cell should undergo cell division or autophagy (self-eating to renew cell components and inhibit senescent cells). As we age, overactive mTor reduces quality control and damaged cell components are not renewed. Inhibition of mTor is shown to extend health span and lifespan [29190625] [34718162] [31316753].

    • Inflammation: aging is marked by chronic inflammation and visceral fat further promotes inflammatory signals. High levels of pro-inflammatory markers in blood predict risk of cardiovascular disease, cancer, frailty, morbidity and decline of cognitive function. Decreasing inflammation shown to lower risk of various diseases [31806905] [30496103].

    • Supercentenarian genes: certain genetic factors influence longevity and decrease risk of cardiovascular, metabolic and neurodegenerative diseases. Identifying these genes helps us to develop compensatory lifestyle interventions to bridge the genetic differences between those lucky individuals with exceptional longevity and the rest of us [31690828] [31109447].

    Figure 2: Lifespan differences between non-supercentenerians and centenerians relative to healthy environment. The aim of anti-aging strategies to emulate super-centenarian biology in non-supercentenerians.