Longevity Science, Anti-Aging Drugs, and the Beauty of Cell Biology
It is not just the quality of longevity science breakthroughs that are exciting, it is the increasing pace of progress.
The beautiful complexity of life is still far from being unravelled. Medicine has yet to accept aging as a root cause of disease that can be targeted. Add a popular press keen to paint longevity as the selfish goal of spoiled billionaires, and you start to see the challenges.
Genetic pathways, signalling mechanisms, novel drugs, gene therapies and the root causes of the diseases of old age are being uncovered all the time. Funding from tech giants, sovereign wealth funds and crowdfunding are increasing the pace of new discoveries.
Once you dig into the breakthroughs, you’ll see that healthy aging is possible right now, and that extending active lifespans is all-but inevitable.
This section of the Age Well Times covers the research, drugs and background longevity science making all this possible.
What is Aging? And What Makes Longevity Scientists Believe They Can Reverse it?
When I was first asked the question ‘what is aging?’ I naturally focused on the visible signs of getting older.
Wrinkles, grey hair, and eventually a stooped back.
It only takes a moment to realise that these are not definitions of what aging is at all. They are its symptoms.
Aging itself is a process, or collection of processes, which take place in our cells, organs, and tissues. It turned out that clearly defining aging is not as simple as you might think.
The debate among longevity scientists is nuanced.
Here is a summary of the key theories:
- The Nine Hallmarks of Aging: Instead of a single marker of biological aging, this concept states that there are nine hallmarks, or measurable factors. They are: Genomic instability, telomere shortening, epigenic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial disfunction, cellular senescence, stem cell exhaustion, altered intercellular communication.
- The Information Theory of Aging: Popularised by Dr David Sinclair in his book ‘Lifespan,’ this theory focuses cells losing their ability to perform specific roles. Over time accumulated epigenetic damage leads to reduced functioning and eventually ‘exdifferentiation’ from specific cell roles.
- Disposable Soma Theory of Aging: A programmed theory based on evolutionary biology. The idea is that we age and die after our peak reproductive years as that is what was best for the specifies over millions of years of evolution. Death of older individuals was a way to free up vital resources to younger generations
- Theory of Antagonistic Pleiotropy: A different angle on evolutionary biology. This theory states that genes are optimised for our reproductive years at the expense of post-reproductive years. Adaptions which boost the chances of having offspring are what cause the symptoms of aging, and ultimately our death.
- Damage Accumulation Theories of Aging: There are multiple ideas that share the damage-accumulation concept. DNA damage beyond our ability to repair, oxidative damage from free radicals and the breakdown of cellular signalling pathways or mitochondrial function are all examples. Telomere shortening with the resulting cellular senescence is a recent example of a damage accumulation theory of aging.
Longevity Science: Will Aging Ever Be Solved?
Over and above individual definitions is the debate on whether aging can be solved at all. The bookends of this debate are that 120 is our evolutionary maximum, or conversely that effective immortality is in our future.
While I’m naturally cautious, the quality of science and accelerating pace of discoveries are hard to deny. With money, brilliant researchers, and the power AI – I’m optimistic that by the time we hit the 2030’s there will be measurable breakthroughs in longevity.
Whether society is ready – particularly when it comes to sustainable lifestyles – is a question we should all be addressing right now.
The Thorny Problems of Measuring Biological Age
Clinical trials for longevity interventions would take a prohibitively long time to complete if we waited for data on when each participant died.
Instead, researchers use measurements which estimate biological age.
As with everything else in the bio-science field, aging clocks are controversial.
The issue is that we can compare specific measures (for example DNA methylation, inflammation markers) against the average for people at different ages. I could have DNA methylation of a 35-year-old, yet still die at a decidedly average 83. Other biomarkers, functional measures and organ health might point to a different biological age.
Let’s pick an extreme example, I could have low DNA methylation and enough plaques in my arteries to be a major heart attack risk.
Individual clocks are useful, especially in early-stage trials.
They are also useful for individuals to measure the effects of longevity habits. A simple DNA methylation test once a year will show whether your new food, sleep and exercise habits show promise at a cellular level.
Find out more on the many measures of aging, from Horvath Clocks to the newest multi-functional measures, in this page on measuring biological age.
Longevity Drugs: Promising Compounds and Surprising Supplements
Whatever the snake-oil salespeople might tell you, there is no miracle cure for aging – at least for now.
That said, promising longevity drug candidates are already showing results in formal clinical trials.
Some are prescription drugs – while others are compounds found in food. With new cellular pathways to investigate, accelerated discovery using AI and the first clinical trials directly measuring aging, the future is bright.
Again, the cellular mechanisms that provide life are unfathomably complex.
We simply don’t know the second, third and ninth order effects of many compounds.
At least for now.
Types of Longevity Drugs
Here are the main categories of longevity / anti-aging drugs.
- Scarcity Mimetics
- Telomere / Telomerase Boosters
- Mitochondrial Health Boosters
- Antioxidant / Anti-inflammatory Drugs
- NAD precursors
Add to this list new compounds targeting novel gene pathways, or focused on signalling mechanisms, specific tissues, or even microbiome populations. Next add interdependencies. What happens if you take more than one type of each drug? Do they work together, multiplying the effect?
My introduction to longevity drugs page covers the key anti-aging drugs – and the most promising areas of research.
Personally, I set the safety bar super high for any new anti-aging drugs. With so many ‘unknown unknowns,’ the risk of one mistake undoing years of healthy living is too big. You can follow my personal journey with healthy aging drugs and supplements in my longevity blog.
Longevity Science: Popular Anti-Aging Drugs
Below is a list of the most popular anti-aging drugs:
Metformin: This is a popular treatment for pre-diabetics. It has a modest effect on extending lifespan in animal models. Metformin is the focus of the TAME clinical trial, which will measure aging.
Rapamycin and mTOR
Rapamycin: The leading longevity candidate is approved as an immune suppressant for organ transplant patients. Multiple clinical trials are underway to demonstrate the dramatic anti-aging effects already demonstrated in mouse models.
Quercetin: A natural flavonoid, this is a powerful anti-inflammatory and antioxidant. It has a measurable effect on boosting NAD levels (which naturally decline with age). Quercetin increases skin elasticity and reduces wrinkles.
Fisetin: Another naturally occurring polyphenol. Fisetin is more than just a powerful antioxidant. It demonstrates powerful senolytic properties – reducing the harmful effects of senescent cells.
Resveratrol: Famous as a component of red wine, Resveratrol is associated with SIRT1 activation – alongside its powerful antioxidant and anti-inflammatory properties. Clinical data links this drug to obesity, and inhibition of carcinogens – as well as mitochondrial heath. This compound is controversial, with mixed data in trials.
NMN / NR / Niacin: NAD+ is essential to the movement of electrons (the energy that powers life) inside our cells. It declines with age, and in obese people. Boosting NAD+ has positive effects on multiple age-related diseases. You can’t directly replace it, as NAD+ is broken down during digestion. Instead, a class of drugs called NAD precursors are used. They include NMN, NR and Niacin.
This is just the tip of the longevity drugs iceberg. You will find explainers of many more drugs and compounds here at the Age Well Times.
My personal hope is that when we look back in five years, some of these compounds will be in widespread use to control the mechanisms of aging – and many new candidates will be in clinical trials.
Supplements for a Longer, Heathier Life
Over the counter supplements range from the mundane (think Vitamin C, or zinc) to the novel.
Beneficial compounds including sulforaphane, antioxidants and natural senolytics are found in food. Add supplements which aid sleep, help us exercise and replace hormones that decline naturally with age – and you get a lot of ‘quick wins.’
Of course, nobody wants to waste money on aging supplements which are ineffective.
My detailed overview of longevity and healthy aging supplements breaks through the science, snake-oil and risks of deficiency in vital minerals.
The Popular Press is Anti-Supplement
The corporate press is quick to push any paper which casts doubt on the effectiveness of supplements. A recent, and hugely damaging campaign railed against vitamin D supplements.
What they miss is that having low levels of key vitamins, minerals and specific hormones is the much bigger risk.
For example, an average person might have safe levels of zinc. A study using only people with high levels will quickly show that supplementation is ineffective. However, someone with low levels of zinc will have a dangerously compromised immune system. Chronic inflammation, viruses and autoimmune disease are downstream of this. All of which contribute to aging.
I will give the corporate press one point. People with terrible diets, obesity and destructive habits like smoking or excessive drinking are unlikely to benefit much from an over-the-counter multivitamin.
Longevity Science Research: Aging as a Disease vs the Diseases of Aging
Aging is a not disease in the view of the WHO and global medical funding bodies – at least for now.
Research grants into the diseases which result from aging dwarf the money available for studies into the mechanisms of aging itself.
That is starting to change, slowly.
The TAME study has split longevity scientists. This is the first clinical trial funded by the NIH which specifically measures aging. It uses a safe diabetes drug called Metformin. It is the choice of Metformin which splits the community. With only negligible effects in animal models, other drugs (Rapamycin / NMN) are considered better candidates.
My view is that TAME is important, with even a small effect setting a president that aging is something that can be specifically targeted.
Hopefully, some of the private funding from the likes of Altos Labs, Hevolution Foundation, VitaDao and others will make longevity science breakthroughs too compelling for the WHO to ignore.
Here at the Age Well Times I will highlight breakthroughs in both the research and the approach to funding.
Longevity Science: Understanding Cellular Biology Will Boost Your Healthy Aging Habits
It is one thing to know that eating certain foods is ‘bad for you.’ Drill down into the details of what is happening to your cells, you get a fresh perspective on how the damage is caused.
For me, understanding the chain reaction of damage that sugar causes was a massive step when it came to resisting the ever present temptation of excessive chocolate.
The complexity of individual cells, the mechanisms which control which genes are expressed and the signalling pathways between and inside cells is amazing. The interconnectedness of processes amplifies this complexity to mind-blowing proportions.
I have covered the key processes, gene groups that researchers are targeting and background facts in explainer articles here at the Age Well Times.