How the Agreed Hallmarks of Ageing Interact
How old you are and how many times Planet Earth has flown around the Sun are not the same thing.
People born on the same day can have a hugely different biological age decades later.
While the number of candles on your birthday cake are an accurate measure of chronological age (depending on how polite your friends and relations are), hallmarks of biological aging are a little more complicated.
Each hallmark is a measurable factor that progresses as we age. They are interdependent, moving together. Ageing hallmarks are also predictive of chronic conditions and life expectancy. They are also reversable – at least to an extent.
Gerontologists use nine hallmarks of ageing.
This interaction can be through shared causes, shared pathways or via knock-on effects.
You’ll find each of the nine ageing hallmarks explained on this page.
Image Credit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/
Nine Hallmarks of Ageing: Overview
Hallmark #1 – Genome Instability
Oxidation is happening millions of times per second in our bodies. Reactive Oxygen Species (ROS) are released as part of the cellular energy cycle. They are triggered by environmental toxins. We have checks and balances, though some level of DNA damage is inevitable.
Processes of DNA repair, and autophagy for damaged cells prevent genome instability becoming dangerous. As we age, the ability to repair unstable genes deteriorates.
Genome instability is measurable, via DNA Methylation clocks. The Horvath Clock is the most popular measure – though newer and more accurate versions are available.
Hallmark #2 – Telomere Shortening
Telomeres are caps on the end of our DNA.
They perform a key role – preventing DNA replication errors when cells divide. There are individual differences in the length of telomeres. The rate at which they shorten is controlled by both individual and environmental factors.
As we biologically age, our telomeres get shorter. There are ways to slow the shortening of telomeres, via diet changes and / or supplements. Telomerase repairs cell telomeres naturally. Supplementing telomerase is not recommended, as cancer cells may benefit from this. Antioxidant foods are positively associated with longer telomeres.
#3 – Epigenic Alterations
The Epigenome is made of proteins which determine which part of the DNA is used for that cell’s specialist role.
After all, the DNA of every cell, from brain neurones to liver cells is identical. Our epigenome blocks some parts of the DNA. It allows other parts to create proteins that fulfil its specialist role.
If the epigenome makes cells different, alterations in the epigenome stop cells being specialists. You may know this better as ‘exdifferentiation’ – via Dr David Sinclair and his ‘information theory of aging’ in the book Lifespan.
As we age, damage to our epigenome accumulates. Cells which are unable to do their role weaken our key cellular functions.
#4 – Loss of Proteostasis
Cells need multiple organelles and proteins to function.
While the epigenome is involved in the transcription of DNA, damage to the other parts will also lead to loss of cellular function. Ageing causes misfolded proteins. It also causes errors in protein biosynthesis. Over time, our mechanisms for removing problematic results of these errors diminishes – and loss of cellular function increases.
#5 – Mitochondrial Disfunction
Mitochondria have their own DNA.
They control the ATP / ADP cycle, which is how we store and use energy at the cellular level. Without this cycle, we die in seconds. The DNA of mitochondria suffers from oxidation, and their efficiency decreases. NAD (and it’s precursors) are critical for this energy cycle.
Knock-on effects are wide-ranging. Energy is needed for all the processes listed here – mitochondrial health is life-critical.
#6 – Deregulated Nutrient Sensing
Cells react to the levels of glucose, amino acids, fatty acids, and other messenger molecules.
Ageing reduces their sensitivity to these messengers. When specialist cell types are no longer triggered to perform their function, downstream processes are disrupted.
Pathways that become deregulated include Insulin, IGF-1, mTOR and AMPK. Each has complex chains of follow-on reactions.
#7 – Cellular Senescence
Cellular Senescence creates ‘Zombie Cells.’
These cells stop performing their specialist roles. Instead of being recycles and reused to create new, healthy cells – they are now zombies. Senescence is dangerous. Those cells send out SASP (senescence associated secretory phenotype) molecules, which are inflammatory. They will also induce senescence in neighbouring cells, creating a cascading effect.
Senescent cells accumulate with age. The low-level inflammation is itself aging – a vicious circle.
#8 – Stem Cell Exhaustion
We generate more than 300 billion cells each day. Stem cells are key. They are the master cells, with no specific role, they can become blood, brain, or lung (or many more roles) cells as needed. As we age, the number of stem cells diminishes. The speed at which they can divide slows too. There are strategies for retaining and rejuvenating our stem cell populations.
Inducing regular cells to become stem cells is a major line of longevity research. These are the Yamanaka Factors.
Hallmarks of Ageing #9 – Altered Intercellular Communication
This is an extension of the deregulated nutrient sensing covered above. Nutrient levels are a primary driver of metabolism. There are 100’s more ways in which cells communicate. Signalling molecules include markers inflammation. Inflammaging is chronic low-grade inflammation. This damages healthy cells and is net aging to our entire bodies.
Nine Hallmarks of Ageing: How the Hallmarks Work Together?
You’ll quickly see from the list above that the nine hallmarks of ageing overlap.
Get into the details and the mind-blowing complexity (and beauty) of our biology quickly reveals itself. As we age, the cascading effects of each system malfunctioning will damage others – creating a vicious cycle what leads to our death.
The big take away is that treating any one hallmark alone is insufficient for longevity. All the hallmarks must be slowed or reversed to extend our healthy lifespan.
Scientists including Charles Brenner state that biology is too complex for there to be a simple, single ‘cure’ for ageing. It is the myriad interactions, disorders, and potential for breakdown of life-critical processes that they are referring too.
I believe that health span extension will occur slowly and surely.
I also agree with those who recommend caution. Solving one factor behind aging could easily uncover five more. Let’s be optimistic, while acknowledging the best we can do right now is to optimise what nature gave us though sleep, exercise, and healthy eating habits.
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