4 Ways to Prevent Premature Ageing

Let’s face it, the inevitability of ageing is both disturbing and a comfort. We know that everyone on the planet will eventually die, while maintaining hope that the end is quick and painless.

What if we could guarantee excellent health, right up to the moment of death?

Imagine how much happier we would all be, if our final years were active and productive, not to mention the enormous saving on healthcare and specialist accommodation.

The pursuit of anti-ageing products has driven the pharmaceutical industry for decades. Even before the advent of industrialised research and development teams, travelling snake oil pedlars sold magical elixirs that claimed to prolong life or reverse the effects of ageing. The truth is that no amount of moisturiser or tonics can prevent ill-health or the gradual decline of our tissues and organs.

How do cells age?

The mechanics of ageing are complex and are influenced by a great many personal factors, making it difficult for any drug to halt the deterioration. Our body’s ability to repair itself, relies on creating an exact copy of DNA for the new cell. Each time the cell divides, the protective end caps on our chromosomes, or telomeres, get a little shorter until they are no longer able to function. This is called the Hayflick Limit, after the American anatomist, Leonard Hayflick. When the cell can no longer replicate itself, it becomes senescent, or in easier terms, it experiences cell death.

There are other ways that a cell can achieve senescence, notably through mutation of genetic materials or through a damaging oxidative process, but suffice to say that our cells have a particular lifespan. When they die, they wait to be destroyed by other processes or sit in a state of limbo, secreting harmful proteins that can cause low level inflammation to the healthy cells around them. If these limbo cells are allowed to build up, they eventually cause tissue damage.

1. Pharmaceutical Compounds

Latest research techniques in the ageing field, have skewed their focus away from outdated notion of increasing lifespan, to improving health span instead. The change from the quest for immortality to vitality, is mainly in response to an ageing population who frequently spend their final decades in healthcare facilities suffering from a range of debilitating and degenerative diseases.

One such project at the Mayo Clinic in Minnesota, took senescent cells from old mice, and transferred them into young mice. Those young mice went on to age prematurely, and showed symptoms of diseases associated with the elderly. Lynne Cox, a biochemist at the University of Oxford states that; “If you remove senescent cells from old mice, they get better, they rejuvenate.”

With this premise in mind, the field of removing these limbo cells has spawned a whole raft of new studies into creating senolytics, to clear out the dead or dying cells and their waste products. One drug trial is just a few months away from obtaining approval for use on humans.

These drug companies are not just aiming for a sprightly older generation, they are actively searching for methods to target age specific diseases too. Idiopathic pulmonary fibrosis, a lung condition associated with the build-up of senescent cells, may also be eased by these senolytic compounds. A promising study conducted in January at the Mayo Clinic used two senolytic drugs, a leukaemia treatment called dasatinib along with the plant extract, quercetin. The fourteen people on the trial were not cured, but showed significant improvement.

Another study is underway trialling senolytics on osteoarthritis suffers, while other companies are attempting to kick-start senescent cells back into life with seno-modifying drugs. Further corporations are attempting to super-charge the effectiveness of white blood cells in their patrols around our bodies eradicating the dead cells.

Either way, the race to perfect the treatment of senescence is exciting. Whichever drugs giant gets there first will revolutionise healthcare as we know it, and generate billions in revenue as a result.

Senolytics isn’t the only game in town. An equal number of research teams have turned their attention to the harmful proteins released by limbo cells. One is called mTOR, or mechanistic target of rapamycin, and is known to be involved in cell ageing. Rapamycin is a drug used on transplant patients, but was later found to extend lifespan in worms and mice. Further study showed it was reacting with a protein complex in the cells.

This protein is a nutrient sensor of sorts. Scientists such as Mannick, from the drugs company resTORbio, claims that this protein is activated when you eat, prompting new cell division. When no nutrients are sensed, it switches off new cell growth, and activates protective processes. One of these protection mechanisms is autophagy, where old cells are dismantled and recycled for energy, therefore ridding the tissues of a harmful accumulation of senescent cells This begs the question of whether senolytic drugs are actually required, when starvation brings about a similar outcome.

There is also the problem that mTOR has a habit of getting stuck in the on phase as we get older. Either way, clinical trials on mTOR controlling drugs are yet another branch of health span medicine striving for board compliance ready for manufacture and sales.

One such mTOR inhibitor is about to launch its product without clinical human trials. It combines a number of existing chemicals which are ‘generally recognised as safe’ by the US Food and Drug Administration. Since it is food safety compliant, it can be sold as a supplement. If their lofty claims prove false, and the marketing generates a negative backlash, it could easily damage funding streams of those studies with more rigorous trials for some time.

Young blood and stem cells are another line of enquiry in the area of ageing. While the hype about blood plasma transfusions appear to be true, it is a dangerous and unregulated practice. It started in the 1970s, when biologists hoping to discover more about conjoined twins, plumbed the vascular systems of two mice together. They discovered that older mice regenerated many of their ageing biological systems, while the younger mice deteriorated and showed accelerated ageing. Recent experiments at Stanford University confirmed the older studies. In fact, injecting plasma from young people, or from umbilical cords, will rejuvenate mice. Not only has this led to an unprecedented number of risky transfusion services, but has triggered a slew of new investigation by research teams, to isolate the proteins at work. One company, Elevian is working on an age associated protein called GRF11, while another, Alkahest, is targeting a protein that could successfully treat an eye condition.

All these studies and theories are fascinating, but will no doubt take decades to reach market, if at all, and will probably be too costly for the average person. There are, however one or two things to alleviate the natural build-up of senescent cells in the body.

2 – Intermittent Fasting

Periodic fasting has shown some promising results in the field of ageing, but there is a fine balance to be maintained, since crucial repair nutrients are still required for optimal health. Dr Ming-Hui Zou, at Georgia State University, writes extensively on this subject, focusing on the regenerative properties of the cardio vascular system and bone density.

"We found this compound, β-Hydroxybutyrate, can delay vascular ageing," Zou says. "That's actually providing a chemical link between calorie restriction and fasting and the anti-ageing effect. This compound can delay vascular ageing through endothelial cells, which line the interior surface of blood vessels and lymphatic vessels. It can prevent one type of cell ageing called senescence, or cellular ageing."

This compound, β-Hydroxybutyrate, is a ketone released by the liver from fatty acids during fasting, starvation, low carbohydrate diets and intensive, prolonged physical activity. The ketone induces cell division, thus rejuvenating the lining of the vascular system. In so doing, Zou claims that a younger circulatory system would prevent the onset of age-related cardiovascular diseases and others such as Alzheimer’s and cancer. Interestingly though, Zou does not mention factors such as promoting cell division of cancerous cells or the Hayflick Limitation to the number of times a healthy cell can divide before cell death.

3 – Rigorous exercise

Hodson et al, at the University of Birmingham, has linked resistance exercise with the translocation of mTOR in muscle tissues. The Birmingham team traced the locations of two distinct forms of mTOR before and after exercise and feeding. One form regulated skeletal muscle growth, while the second regulated insulin sensitivity. As one would predict, after exercise and feeding, the first type of mTOR had migrated to the edges of the cells, whereas the insulin type of mTOR remained static in the membranes surrounding muscle fibres. This would indicate that prolonged excitation of muscles allows for the removal of mTOR.

Matthew J. Rossman et al, published in the American Journal of Physiology (2017), states:

“Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary ageing, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function.”

Both studies, and many more, state compelling evidence to suggest that even small increases in exercise can inhibit the harmful proteins, and in some instances, reverse the damage of inflammatory responses.

4 – mTOR inhibiting foods

Despite the undesirable name, eating foods rich in spermidine is harmless to try and may yet prove highly beneficial. Spermidine is a known senolytic, and is found naturally in some foods, such as fermented Japanese soy-beans, mushrooms, potatoes, aged cheese, meat, nuts, broccoli, wheatgerm, seeds, and pears.

A 2018 study published in the American Journal of Clinical Nutrition, linked higher dietary spermidine levels to lower mortality rates. Another study conducted at the University of Liege, Belgium, discovered a causal link between spermidine from mother’s breast milk and decreased incidence of allergies in infants. It went as far as stating that those raised on breast milk were unlikely to experience allergic reactions, if the spermidine concentration in the milk was above 13micromolar/millilitre (nmol/ml).

Since levels of spermidine in the body, decrease with age, it is important that nutrition provides a continuous source. Without sufficient quantities, more than just the rate of cell division can be impacted. A South Korean study (P.B.Tirupathi Pichiah et all, 2011), linked spermidine concentration to increased protection of pancreatic cells, which is especially important for those suffering from Type 2 Diabetes. Other researchers have found similar protective properties of this natural mTOR inhibitor within mammalian cardiac tissues and liver function.

So, as ever, diet and exercise seem to be key in maintaining good health into older age. For those of us without a regimented programme of fitness and healthy diets, we may yet be saved by the advances in the biochemical industries. Popping a pill to prevent disease might become the new panacea against ageing, rather than many drugs to combat the symptoms of diseases related to old age.

#senolytic #senescence #ageing

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