The elixir of youth? The key may lie in senescent cells

Extend your life by 36%? Tempting idea, isn’t it! And it’s actually not that sci-fi, because it’s already been done with mice. All they had to do was remove the so-called senescent cells from their bodies. What’s the point?

The cells of all our tissues multiply by dividing. Once in a while they receive a stimulus from the outside to each divide into two new, identical ones. I mean, identical… Unfortunately, that’s only ideally true. In reality, the process of division produces a number of errors that not only reduce the function of a given cell, but can also be potentially dangerous – they can, for example, become the basis of a tumour.

Perhaps this is why the mechanism that prevents cells from dividing indefinitely was created. Each division shortens the ends of chromosomes, called telomeres. The DNA in the telomeres carries no genetic information, it does not form proteins, it just contains a repeating sequence of nucleotides (the building blocks of DNA). At each division, a few of these nucleotides are lost, so the telomeres gradually shorten. And when their length reaches a certain critical point, which occurs after about 50 cell division cycles, something strange happens to the cell. It doesn’t die directly, but it goes into a state called senescence.

When a cell becomes a zombie

The senescent cells live on, they continue to undergo metabolic processes, but they can no longer divide. On the one hand, this is fine – they have already undergone a large number of divisions, during which a large number of errors have accumulated, and if they were to continue dividing, they could become the basis of a malignant tumour. But at the same time, it’s not such a win either. In fact, senescent cells resist apoptosis, or cell death, quite ably, so they accumulate in the body over time. And it is the increase in the number of senescent cells in the body that is closely related to ageing.

The older the organism is, the more of these cells its tissues contain. Therefore, recently published experiments on mice, which focused on eliminating senescent cells from their bodies, look very promising – the researchers achieved this by using so-called senolytic agents, specifically mixtures of dasatinib and quercetin. Consequently, the aged mice experienced a significant increase in lifespan – from an average of 36%, or more than a third! At the same time, they showed improvements in some fitness parameters (walking speed, endurance, grip strength) and health status. It was simply a true elixir of youth.

Local administration of senolytic agents has also led to improvements in atherosclerosis and arthrosis in other studies.

Why are senescent cells harmful?

Senescent cells do not harm only by accumulating in tissues. It is true that they not only look slightly different from their young counterparts (they have a flattened shape and a different internal structure), but above all they also behave differently. Particularly problematic is the fact that they produce tiny molecules called cytokines that significantly increase the overall level of inflammatory processes in the body. And it is inflammation that is at the root of many serious diseases in the body – for example, cardiovascular disease, diabetes, arthritis and some cancers.

If senescent cells are present in large numbers in the blood vessels, they cause their narrowing. When they accumulate in the prostate, they contribute to its hyperplasia or overgrowth, in the joints they promote the development of arthrosis… The accumulation of senescent cells in the skin, for example, is also related to the formation of birthmarks – their incidence also increases significantly with age.

The accumulation of senescent cells also disrupts homeostasis and reduces the regenerative capacity of tissues, which also contributes to the acceleration of the aging process. Importantly, from an epigenetic perspective, they affect the activity of a number of important genes in surrounding cells, particularly in the area of histone modification, through cell signalling.

Paradoxically, senescent cells can also contribute to cancer. Each cell secretes substances into its surroundings that influence the so-called cell signalling of the surrounding cells. However, the substances produced by senescent cells are different from those produced by young cells – for example, in addition to the aforementioned inflammatory cytokines, they also produce molecules that may contribute to the formation of tumours in their surroundings.

However, senescent cells are not only harmful, but can play an important role in the wound healing process, for example. In fact, when a wound occurs, the cells in the surrounding area enter the senescent state much faster than those in the intact tissue. In doing so, they start to produce the growth factor PDGF-AA, which promotes wound closure. However, the negative effects are significantly more pronounced.

How to keep senescent cells at bay?

Senescent cells arise in the body quite naturally as more and more cells go through the aforementioned fifty or so cell cycles. Therefore, it is also true that the older a person gets, the more senescent cells there are in his body.

But then there are also factors that promote senescence. These generally include any stress, especially oxidative stress, i.e. excessive production of free radicals. Senescence is also accelerated by some negative epigenetic processes – i.e. reactions that take place in the body as a result of external stimuli (lifestyle, nutrition, exercise, environmental toxins, etc.) and which are capable of switching off or on some genes in our DNA. An important role is played by the genes by which the body produces enzymes called sirtuins, whose optimal levels are important for fighting ageing. Premature cellular senescence is also an unpleasant side effect of cancer treatment with chemotherapy.

Senescence is also affected by the level of an enzyme called telomerase, which slows the shortening of telomeres during cell division. However, a significant boost in its production is not desirable – it occurs naturally only in stem and germ cells, while in other cells its increased level is undesirable because it can promote tumour processes.

What can help?

Basically, everything we call a healthy lifestyle is important in preventing excessive production and accumulation of senescent cells. Nutrition is key. Here, excessive intake of carbohydrates in particular, as well as general overeating, are of particular concern. On the other hand, fasting, including intermittent fasting, as well as a general restriction of calorie intake, are positive. All this will promote the process of autophagy (a state in which the cell “eats” itself), which can help to eliminate senescent cells.

Regular exercise is also important, as well as reducing stressful stimuli.

Currently, clinical trials of drugs that can remove senescent cells from the body are already underway, but natural substances can also be of great service to us. It is particularly worth focusing on substances with epigenetic effects, which can also regulate, for example, excessive gene methylation, another important cause of ageing.

Sufficient intake of antioxidants, harmonization of sirtuin production, as well as support of immunity are also important, because immune cells can eliminate senescent ones to a certain extent.

Useful dietary supplements

Quercetin – this polyphenol, found in many plant foods, not only has significant antioxidant effects, but can also protect cells from going senescent, and has even been shown in cell culture studies to restore the ability to divide in cells that have already reached senescence. What’s more, it also has anti-cancer effects.

EGCG – epigallocatechin gallate, a polyphenol contained in green tea, can effectively counteract premature cell senescence, thanks to its combination of antioxidant and epigenetic potential.

Curcumin – a dye from turmeric root promotes the removal of senescent cells through the immune system. It also has a positive effect on all basic epigenetic processes, has an anti-cancer and anti-inflammatory effect. For better absorption and utilization, it should be taken together with black pepper piperine.

Vitamin E – this fat-soluble vitamin has senolytic activity (promotes the removal of senescent cells from the body) and has anti-tumor activity.

Resveratrol – a dye found in red wine skins, for example, is a known activator of sirtuins, which are associated with the aging process.

Genistein – this isoflavonoid contained for example in soy and other legumes has significant antioxidant, anticancer and antidiabetic effects, increases telomerase activity, slows the aging process and is characterized by senolytic action.

However, a number of other substances also show senolytic activity:

• sulforaphane and phenethyl isocyanate, which are found in cruciferous vegetables (e.g. broccoli, kohlrabi, cauliflower and kale),
• allicin contained, for example, in garlic,
• fisetin, a polyphenol found in many fruits and vegetables (e.g. strawberries, mangoes and cucumber),
• triptolide (a substance from the plant Tripterygium wilfordii, which is used in Chinese medicine),
• and even the cannabinoids in marijuana.