The genes that you and I have from cradle to grave are mostly the same. But we certainly look and feel different at each stage of life. And we heal differently given the same type of injury.
While the first and second term human fetus is likely to undergo surgery without any consequent scars, as soon as the fetus reaches the third trimester and onwards the situation changes without any warning. From this moment on, injuries will heal incompletely and scars will be deposited wherever is needed.
Fibrosis lies at the root of aging. The skin becomes rigid. So do the joints, hence mobility is impaired. The lungs get stiffer and the elderly lose their breath much faster than the young. The heart gets bigger and each new ischemic injury heals with fibrosis.
The excessive deposition of collagen that we call ‘scar’ makes the injured tissue to be incompletely regenerated. The new scar will never have the same physical and chemical properties as the original tissue. And inside the heart, scars will never conduct nervous signals like viable cardiac cells would, hence the increased frequency of branch blocks and arrhythmias in the elderly.
Fibrosis is a hack of nature while lacking a better solution. A solution which mammals have in their first days, but they seem to forget about on their way to adulthood and senescence.
A threshold exists between the time a fetus heals without scars and the time it develops scars post injuries.
This threshold varies depending on:
- the size and depth of the causing injury
- the age of the fetus
- the species itself
And in the human species at least, there are two types of cells with massive influence over this dynamic threshold:
- the platelet
- the fibroblast
You may remember the platelet from old biology classes. It is the cell responsible for stitching up blood vessels so that you don’t bleed to death in case you cut yourself. In mammals like us, platelets are anucleated cell fragments and they express different genes depending on the age of the subject – but don’t all cells do that anyway?
Fetal platelets don’t aggregate. And according to an intriguing review paper, the moment they start to aggregate (or their phenotype becomes adult-like) marks the moment when injuries are healed with scars. And while aggregation is necessary for stopping the leakage of blood, the platelet plug also sends out chemical signals calling other inflammatory cells.
Since fetal platelets don’t aggregate, the fetal response undergoes minimal inflammation, while the healing response in the elderly is often excessive in terms of damage and inefficient in terms of replacing the injured cells. Platelets aggregate in excess in metabolic disorders and autoimmune diseases. And these increase in frequency with age.
Going further on the age scale, the blood of the elderly is more viscous. The elderly are more prone to getting their narrower arteries blocked and platelets have a lot to do with it (but they are not the only factor involved). Drugs that impede the platelets from aggregating are called antiaggregant or antiplatelet drugs. Examples include aspirin and clopidogrel and together with anticoagulants, these drugs represent the bread and butter of geriatrics. And while the use of such drugs is responsible for delaying many cardiovascular deaths, they certainly don’t make the elderly heal without scars.
Which brings us to the next cell involved: the fibroblast. This is the cell responsible for synthesizing the collagen in the scar. And just like the platelet, fibroblasts in fetuses express different proteins compared to fibroblasts in the elderly. The rigidity of the scar itself is determined by a subset of cells called myofibroblasts which are differentiated fibroblasts. Once their role is completed, they commit apoptosis. In some diseases – like the Dupuytrenne disease – they refuse to commit suicide. These differentiated fibroblasts are a rarity in fetuses.
The two types of cells just mentioned – the fibroblast and the platelet – express different genes depending on the age of the subject. Consequently, injuries heal with different results.
And while nobody did comparative gene expression studies in humans before and after the scar-forming threshold (or at least not that I know of), we do know quite a bit about the molecules that are synthesized in the fetal and adult wounds.
My hypothesis is that a mixed chemical formula expressing the fetal proteins and blocking the elderly ones could make a huge leap in solving fibrosis and aging itself.
Such a mixed formula would need to make the elderly cells overexpress :
- hyaluronic acid
- fibromodulin
- metalloproteinases
- TGF-beta 3
- interleukin-10
- type III and IV collagen
- any collagen turnover proteins
and at the same time block the synthesis of:
- Interleukin-1
- TNF-alpha
- TGF-beta 1
- TGF-beta 2
- type I collagen
- platelet-derived growth factor
- interleukin-6
- interleukin-8
and finally block platelet aggregation and the differentiation of fibroblasts into myofibroblasts or at least the selective destruction of the latter.
Such a formula could initially influence the genetic expression of the fibroblast and platelet only and be refined as we understand more about the differences between the fetal scarless and the elderly scar-forming healing process. Comparative gene expression studies would certainly be helpful.
Anca Ioviţă is the author of Eat Less Live Longer: Your Practical Guide to Calorie Restriction with Optimal Nutrition ,The Aging Gap Between Species and What Is Your Legacy? 101Ways on Getting Started to Create and Build One available on Amazon and several other places. If you enjoyed this article, don’t forget to sign up to receive updates on longevity news and novel book projects!
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