The science (not fiction) around ageing
This is a simple, practical guide for our patients to some of the current medications and supplements that are being tried in anti-ageing medicine.
It is not about facials, botox and fillers, masking what is going on inside us on a deeper level. It is not about the psychosocial and lifestyle factors which are hugely important and much has already been written about these things.
For now, we will not be talking about all the beneficial nutrient rich anti-inflammatory foods and pro and prebiotics. We will not be talking about dietary restriction. Although all these things will also improve lifespan in the same way as drugs and supplements work. They increase insulin sensitivity, reduce cell inflammation and oxidative stress. They improve mitochondrial function, reduce diabetes, lower blood pressure and cholesterol.
Hopefully we can answer questions we get asked daily. “What should or could I take? Where from? What doses?”. Firstly, a little bit of science around the theories of senescence and the language you will hear used. This should help to understand how and on what processes in our bodies the medications and supplements we use work.
Telomeres are repetitive DNA sequences at the end of chromosomes to protect the chromosomes from becoming frayed or tangled, each time a cell divides the layers shorten.
They are essential in protecting the integrity of chromosomes and organismal ageing. Specific cells that divide many times have an enzyme called ‘telomerase’ which helps to add the telomeres back to the chromosomes.
Senescent cells are effectively old or run-down cells that have reached the end of their lives or have been damaged beyond repair.
They produce a mixture of cytokines, chemokines, growth factors and extracellular matrix proteases which spread inflammation and are harmful to neighbouring cells.
In our youth, our immune system can clear them out by itself, but as we get older our body does this less effectively, leading them to accumulate and damage other cells. And the presence of a high number of senescent cells have been linked to age related diseases such as diabetes and cancer.
There are currently over 20 different clinical trials of drugs that combat senescent cells (known as senolytics), targeting several different age-related conditions from Alzheimer’s to Osteoarthritis and beyond. Whilst more data is needed, the hope
is that senolytics could be the key to slowing down (not just progression) of specific diseases and ageing more generally.
Senomorphics are another class of drugs being looked at. These instead of killing senescent cells, make them less aggressive.
Mitochondrial dysfunction is also often mentioned. Mitochondria in cells produce energy, they are little ‘powerhouses’ and with age their efficiency declines so they produce less energy and release chemicals that cause cell damage. This contributes to something known as oxidative stress where the body has reduced antioxidant defences.
Chronic Inflammation in the body as we age can also reduce antioxidant defences and reduce immune responses. Chronic inflammation contributes to many age-related diseases.
Proteins play a vital role in the body. Damaged proteins can accumulate in cells causing cell death.
Amyloid is a specific type of folded insoluble folded protein. This is implicated in degenerative diseases such as Alzheimer’s and Parkinson’s.
Autophagy is the process by which damaged protein is removed from cells to prevent toxicity. Dysregulation of autophagy is also implied in age-related diseases.
Epigenetics essentially looks at how external environmental and lifestyle factors can modify how genes are expressed without changing the DNA sequence. It is implicated in various degenerative diseases.
The gut barrier theory of ageing suggests that amongst other things, changes in the gut microorganisms and barrier function promote inflammation by increasing toxins and allowing microbes to enter the bloodstream.
METFORMIN
Belonging to a family of medications called biguanides, Metformin is the generic name of the drug.
It is the first choice of medication prescribed by doctors for type 2 diabetes and pre-diabetes; risk factors for developing heart disease, stroke, and other serious medical conditions.
It has been in use since the late 1950s and is considered to be a very safe drug with little in the way of side effects.
Currently there is a major ongoing clinical trial known as The Targeting Ageing with Metformin (TAME) Trial. This is a six-year clinical trial involving over 3,000 individuals.
It is also widely regarded as a ‘wonder drug’ because of its many modes of action:
It improves insulin sensitivity and metabolism and helps with weight maintenance.
It appears to have strong senomorphic properties making senescent cells less aggressive.
It improves the gut microbiome and therefore helps the immune system.
It decreases inflammatory markers.
It improves bone mineralisation – a modest 7% increase in tissue mineral density is associated with a three-fold increase in bone stiffness and a doubling in breaking strength.
Benefits:
Reduction of osteoarthritis and osteoporosis.
Reduction of coronary heart disease.
Potential effect in reducing the risk of neurodegenerative diseases such as Alzheimer’s. Reduces fatty liver disease.
Risks:
Some people may get mild gastrointestinal upset.
Very rare accumulation of lactic acid in people with underlying kidney or liver disease.
GLP-1 & GIP PEPTIDES
On an almost daily basis we read about Ozempic (semaglutide), which was licensed for diabetics, then Wegovy (also semaglutide), which was licenced for weight loss, and now Mounjaro (tirzepatide).
These drugs cause weight loss by increased insulin levels, appetite suppression, and burning fat. In addition to lifestyle improvements in sleep, diet and exercising, they will play a long-term role in the future of anti-ageing medicine. They may work in anti-ageing by improving mitochondrial function and reducing oxidative stress.
So, what is Semaglutide?
It is an analogue of GLP (glucagon like peptide)-1, which works at receptors in the pancreas, stomach, intestine and nervous system.
GLP-1 increases insulin. Insulin allows cells including muscle and liver to take up glucose and store it as glycogen. GLP-1 also inhibits the production of the antagonist hormone to insulin known as glucagon, which would otherwise cause glucose release into the bloodstream.
GLP-1 slows down gastric emptying, so you feel fuller for longer. This is probably the major source of the common side effects of nausea and constipation. GLP-1 also works centrally on the brain by telling the brain that we are full. This reduces hunger and appetite.
So, what is Tirzepatide?
This, in addition to working on GLP-1 receptors, works on GIP (glucose dependent insulinotropic polypeptide) receptors. These receptors are found in the pancreas, in fat cells and other areas of the nervous system.
Additional effects are due to the burning of fat known as lipolysis including in the central fat deposits like the liver.
It works at receptors for GLP-1 and GIP in the brain further enhancing appetite suppression.
It reduces cholesterol levels.
Side effects are much less common than Ozempic.
Ozempic/ Wegovy vs Mounjaro
Ozempic can result in weight loss of around 15% of your body weight in 12 months. Mounjaro can result in up to 25%. With increasing availability in the UK, it is superior at reducing blood sugar levels and reducing weight.
The inevitable dietary restriction and the need for exercise focusing on increasing muscle mass as opposed to cardiovascular exercise alone will best augment the metabolic effects associated with these hormonal mechanisms.
Benefits:
Reduce weight and all the complications of obesity. Calorie restriction has been shown to combat ageing.
Improve insulin sensitivity preventing and treating conditions like fatty liver, type 2 diabetes and polycystic ovarian syndrome (PCOS).
Tirzepatide has been independently shown in studies to reduce cholesterol levels.
Semaglutide has been shown to reduce heart attacks and strokes independent of its weight loss properties. This might be due to a direct effect on the blood vessels.
There is interesting documentation of reduction in addictive behaviour including drugs, alcohol and gambling.
Protecting the nervous system: GLP-1RAs can help protect the nervous system, which can help with age-related cognitive decline and neurodegenerative diseases. There is an ongoing study at Imperial University, London looking at the effects of GLP-1 Analogues in Parkinson’s Disease.
Anti-inflammatory properties.
Possible reduction in collagen breakdown implicated in ageing.
We can see these drugs being used long term at low doses (perhaps microdoses). I would like to aim, after initial weight loss, towards long term maintenance keeping weight stable, however maintaining all the benefits listed above.
Risks:
Gastrointestinal – nausea and constipation. Very little with tirzepatide.
FISH OIL
Fish oil, derived from fatty fish, like salmon, herring, tuna and mackerel, is rich in omega-3 fatty acids, Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) – essential fatty acids the body can’t make for itself.
These nutrients have anti-inflammatory effects, helping reduce inflammation associated with ageing. Omega-3s also promote cognitive function and heart health, slowing down age-related decline, while supporting skin hydration, leading to healthier looking skin.
Research suggests that omega-3 fatty acids may slow down the process of cellular ageing by protecting telomeres.
Benefits:
Omega-3 fatty acids have anti-inflammatory properties, which can help mitigate the effects of inflammation on the body.
DHA is crucial for brain health. It supports cognitive function and helps maintain the structure and integrity of brain cells.
Omega-3 fatty acids reduce the risk of cardiovascular disease by lowering triglyceride levels, reducing blood pressure and preventing the formation of blood clots.
Fish oil supplements have been found to reduce joint pain and stiffness.
Risks:
May interact with blood thinning medication.
HORMONE REPLACEMENT THERAPY (HRT)
HRT is simply what it says it is. It is used around the menopause when the ovaries essentially go to sleep and stop producing oestrogen.
Lack of oestrogen can produce physical symptoms like night sweats, hot flashes, irregular bleeding, reduced energy levels, dyspareunia and urinary tract infections. There is a loss of muscle mass, bone density and loss of skin elasticity.
There are also significant mental effects including depression, anxiety, mood swings, irritability and lack of libido.
Treatment involves replacement hormones like DHEA, oestrogen, progesterone and testosterone, all aimed to restore hormonal balance. This is mainly given transdermally or orally.
Benefits:
We would suggest starting HRT early to achieve the best effects, as soon as you notice any symptoms or signs.
Symptom relief – HRT reduces common menopausal symptoms such as hot flashes, night sweats, low energy.
Bone health – Oestrogen helps maintain bone density, reducing the risk of osteoporosis and fractures. It improves muscle mass.
Improved collagen levels, elasticity in skin and as such anti-wrinkle.
Heart health – Some studies suggest that HRT may have cardiovascular benefits lowering the risk of heart disease in younger women.
Reduction in colon cancer.
Mood stabilization – HRT improves mood swings, irritability, and anxiety. Although there is an improvement in cognitive function, there have been mixed views regarding reducing the risk of dementia.
Risks:
Increased risk is multifactorial and often related to family history and other associated health issues such as obesity and pre-existing disease.
A very small increase in breast and gynaecological cancers especially with long term use and a family history.
A small increase in the risk of blood clots, especially in women who smoke or have a history of this.
Some studies show a slight increase in the risk of stroke with HRT use, particularly in older women again with co-morbidity.
DEHYDROEPIANDROSTERONE (DHEA)
DHEA is a hormone produced by the adrenal glands. It is a precursor to testosterone and oestrogen, and it plays a significant role in making these sex hormones. Its levels in the body are highest during young adulthood and gradually decline with age.
DHEA is an essential hormone in the body because of its role in the production of other hormones and its potential effects on various aspects of health and ageing.
As an oral preparation it is not a prescription drug, however we think it needs to be used under medical supervision, a little bit like hormone replacement therapy (HRT).
We offer it to pre-menopausal women, and men for its potential beneficial effects. We don’t use it with oestrogen and testosterone HRT. Recently introduced preparations of DHEA can be prescribed (prasterone) to increase local levels of oestrogen and testosterone in post-menopausal women.
Benefits:
Improves skin health in terms of hydration and firmness, reducing the appearance of ageing such as wrinkles and age spots.
Mental well-being – improved mood and memory.
Improvement in bone health in perimenopausal and postmenopausal women.
Improved libido and sexual function.
It may improve the outcomes of egg freezing and in vitro fertilization (IVF) by stimulating ovarian function.
DHEA is often used as an adjuvant treatment in conjunction with other therapies.
Risks:
Hormonal side effects may include oily skin, acne and hair growth.
Avoid if you have heart issues, liver disease or a history of hormone sensitive tumours.
DHEA may interact with medications including antidepressants, antipsychotics, and hormonal treatments.
NICOTINAMIDE MONONUCLEOTIDE (NMN)
Nicotinamide mononucleotide (NMN) is a compound naturally found in the body and serves as a precursor to nicotinamide adenine dinucleotide (NAD+). NAD+ is a coenzyme involved in metabolic processes within cells, including energy production and DNA repair. NMN supplementation aims to boost NAD+ levels supporting mitochondrial function and DNA repair mechanisms both of which are linked to anti-ageing effects.
Benefits:
Enhanced Energy Production – NAD+ is essential for mitochondrial function, where it participates in oxidative phosphorylation, the process by which cells generate energy. By supporting NAD+ levels, NMN may help optimise mitochondrial function, leading to increased energy production and improved cellular metabolism.
Improved Metabolic Health – Studies show improvements in metabolic parameters such as glucose tolerance and insulin sensitivity. This suggests a potential role for NMN in managing metabolic disorders such as type 2 diabetes and obesity.
DNA Repair and Cellular Integrity – NAD+ is involved in DNA repair mechanisms, and higher levels of NAD+ may enhance the cells’ ability to repair DNA damage caused by various factors, including oxidative stress and UV radiation. This could contribute to maintaining genomic stability and cellular integrity, potentially reducing the risk of cancer and other age-related diseases.
Anti-ageing effects – NMN has been studied for its potential anti-ageing effects, with research suggesting that NMN supplementation may help mitigate age-related decline in cellular function and improve overall health span. This includes benefits such as improved cardiovascular health, cognitive function, and physical performance.
Neuroprotective Properties – NAD+ plays a crucial role in maintaining neuronal health and function. NMN supplementation has shown promise in animal studies for its neuroprotective effects, suggesting potential benefits in conditions such as Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders.
Cardiovascular Health – NMN may have beneficial effects on cardiovascular health by improving endothelial function, reducing inflammation, and enhancing vascular integrity. These effects could help lower the risk of cardiovascular diseases.
Longevity – Some studies suggest that NMN supplementation may extend lifespan and improve health span in animal models, indicating its potential as an anti-ageing intervention.
Risks:
NMN is safe when taken in recommended doses.
Can cause gastrointestinal upset.
Can cause flushing.
TESTOSTERONE
Hormone Replacement Therapy (HRT) is the word we associate with women, but HRT is also important in men.
We don’t like the term andropause /male menopause as there is no abrupt stop in hormone production as in women, however, signs and symptoms can develop insidiously. Oestrogen protects against the effects of ageing in women so why shouldn’t testosterone do the same for men? (and in low doses for women).
Testosterone is produced in the testes and adrenal glands and levels peak at age 18 and decline very slowly from about age 30.
What to use? Its personal preference. Gels give an absorption rate of up to 90% and are simple to use at home. Injections can be given every 3 months, so it is your preference.
Benefits:
Improve sexual drive, function and sperm production.
Improve muscle strength and mass, bone density and reduce abdominal fat. Exercise plays an important role here.
Improve mood, lethargy, motivation and possible aggression. There is apparently some association between testosterone levels and different professions.
Risks:
All will be dose dependent. So, if you replace what’s not there (and review) and you feel better, it’s our opinion that its right to use.
Acne and oily skin if too much is given. The latter might be helpful as age makes you lose skin elasticity.
RESVERATROL
Resveratrol is a natural compound found in various plants, particularly in grapes, red wine, berries, cocoa, soy and peanuts. It was first isolated in 1939 in Japanese knotweed and is often used in traditional Chinese and Japanese medicine.
Orally its potential health benefits are due to various mechanisms. These include anti-oxidation, anti-inflammation, and regulating cellular senescence. It is thought to activate sirtuins which are proteins associated with longevity.
Trans-resveratrol is a bioactive isomer and is more effective than resveratrol. Although found in red wine, you would have to drink too much red wine to gain therapeutic doses – based on a therapeutic dose of 500mg of trans resveratrol a day, it’s over 80 bottles a day!
Benefits:
Studies suggest that resveratrol may have positive effects on cardiovascular health by reducing LDL cholesterol and reducing insulin resistance.
Antioxidant properties may reduce the risk of age-related diseases including cancer.
Anti-inflammatory effects.
Skin protection via collagen synthesis, UV protection and regeneration. It is often used topically.
Risks:
Resveratrol is generally considered to be safe.
May cause side effects such as nausea, and headaches with higher than recommended doses.
Resveratrol may interact with blood thinners and drugs broken down by the liver. This should be assessed before starting.
Vitamin D3
Vitamin D is produced by the skin upon sun exposure and is key in the fight against ageing.
It supports bone health by aiding calcium absorption to maintain bone density and reduces the risk of osteoporosis.
Recent preclinical studies suggest that vitamin D exhibits anti-inflammatory effects, including the modulation of genes involved in immune regulation and pro-inflammatory factors.
Phytochemicals in fruits and vegetables upregulate the immune benefit and absorption of Vitamin D, maximising the potential health benefits.
Benefits:
There is a close interaction between vitamin D and the immune system. Vitamin D may have a direct impact on the body’s ability to fight off infections and diseases.
It aids calcium absorption and bone mineralisation, so helps maintain bone strength and density. Adequate intake is essential for optimal bone health.
It preserves muscle strength and mobility.
Maintains the gut barrier by the production of antimicrobial peptides and modulating gut hormone secretion.
Risks:
Vitamin D supplements are safe when taken in recommended doses.
Vitamin K2 plays a busy role in activating proteins essential in the fight against age-related diseases. Vitamin K2 helps with blood clotting so helps with wound healing. It strengthens bone health when used in combination with vitamin D3.
Benefits:
Vitamin D3 enhances calcium absorption in the intestines, while vitamin K2 aids in the activation of osteocalcin, a protein involved in bone mineralisation. Together, these vitamins contribute to maintaining optimal bone density and reducing the risk of fractures.
Vitamin K2 has been associated with a reduced risk of arterial calcification which is a risk factor for cardiovascular disease. Vitamin D3 also plays a role in cardiovascular health by helping to regulate blood pressure. The combination of these vitamins may have synergistic effects in promoting heart health and reducing the risk of cardiovascular events.
Some research suggests that vitamin D3 and K2 may play roles in cognitive function and reducing the risk of neurodegenerative diseases. They may help protect brain cells from oxidative stress and inflammation.
Both vitamin D3 and K2 have anti-inflammatory properties, which can help combat chronic inflammation age-related diseases.
Risks:
Vitamin K2 is safe when taken in recommended doses.
It can interact with blood thinning medication.
STATINS
Statins reduce harmful LDL (low density lipoprotein) and total cholesterol levels. They do this by reducing the production of LDL. They also increase beneficial HDL (high density lipoprotein) levels. They reduce triglyceride levels.
Overall they reduce the build-up of plaque in the arteries which can lead to heart attack or stroke. They also reduce the risk of developing diabetes and liver disease.
Preliminary research suggests that statins may have effects on telomeres, the protective caps at the end of chromosomes that shorten with age. Shortened telomeres are associated with cellular ageing and increased risk of age-related diseases.
Statins may help maintain telomere length or slow down the rate of telomere shortening. They may upregulate the expression of the Klotho gene and may play a protective role in age-related diseases.
Benefits:
Improved cardiovascular health in all ages. Some studies show that with a one-unit reduction in harmful LDL Cholesterol, the incidence of heart attack is reduced by 25% and stroke by 21%.
May reduce the risk of Alzheimer’s as cholesterol affects the protein (Amyloid Beta) that causes Alzheimer’s disease.
It is anti-inflammatory as it enhances the benefits of nitric oxide which improves blood flow and slows the progression of all cardiovascular diseases including vascular dementia.
Cognitive improvement. The evidence regarding the association between statins and cognitive impairment is mixed, with some studies suggesting an improvement in cognition, some a decline and some no significant association.
Risks:
Muscle pain which although very rare, often goes away by swapping one statin to another.
Statins work by promoting LDL cholesterol removal through the liver which can cause an elevation in liver enzymes. Again, this is rare.
RAPAMYCIN
Rapamycin, a compound discovered in the soil of Easter Island, has garnered significant attention for its potential to extend lifespan and improve healthspan.
Initially used as an immunosuppressant in organ transplants, rapamycin’s ability to inhibit the mTOR (mechanistic target of rapamycin) pathway has opened new avenues in understanding and addressing ageing.
Discovery and Initial Use
Rapamycin was discovered in the late 1960s by Canadian researchers on Easter Island. The compound, produced by the bacterium Streptomyces hygroscopicus, was initially recognised for its antifungal properties and later for its immunosuppressive effects, leading to its use in
organ transplants under the brand name Rapamune (Sirolimus).
Mechanism of Action
Rapamycin inhibits the mTOR pathway, which regulates cell growth, metabolism, and cellular ageing. By inhibiting mTOR, rapamycin shifts the body from a state of growth to repair and maintenance, promoting cellular clean-up (autophagy) and reducing inflammation.
Current Research and Future Directions
Several clinical trials are underway to evaluate rapamycin’s effects on human ageing. These studies aim to determine the optimal dosing and assess the drug’s safety and efficacy in extending healthspan and lifespan.
Researchers are also exploring next-generation rapalogues and combination therapies to enhance the benefits while minimising risks.
Conclusion
Rapamycin holds significant appeal as a potential anti-ageing drug. Its use should be clinically-led and closely monitored. Ongoing research will provide more insights into its long-term safety and effectiveness, adding to the significant evidence from animal studies. However, it remains a promising and viable option for extending human lifespan and healthspan.
Benefits:
Animal studies have shown that rapamycin can extend lifespan by up to 25%. Its effects appear significant even when administered later in life. It also delays the onset of age-related diseases such as heart disease, cancer, and cognitive decline.
Rapamycin appears to improve healthspan by promoting autophagy, reducing chronic inflammation and preventing cellular senescence.
At lower doses used for anti-ageing, rapamycin seems to enhance elements of immune function in older adults, improving their response to infections and vaccines.
Evidence from animal studies suggests rapamycin may help
prevent neurodegenerative diseases such Alzheimer’s and Parkinson’s Disease.
Risks:
At higher doses, rapamycin can suppress the immune system increasing the risk of infections.
Prolonged use can lead to glucose intolerance and insulin resistance, potentially increasing Type 2 Diabetes risk. NOTE: The use of another anti-ageing, anti-diabetic medication, Metformin, can mitigate this.
Some users report mouth ulcers as a side effect.
Though there is no evidence of significant harm, the long-term effects of rapamycin use for longevity are not yet fully understood.
DISCLAIMER
This information does not include all medications and supplements used in the rapidly evolving science of anti-ageing but represents commonly used products that we are familiar with at our practice.
The information is very much our personal view and does not necessarily concur with all current scientific research.
The most important things in maintaining yourself remain a good diet, a good sleep pattern, regular exercise, avoiding excessive alcohol and smoking and looking after your mental health.
To enquire further about our Anti-Ageing Programme, Preventative Health Assessments, or GP Services:
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