Written by Eva Hamrud, PhD
November 3, 2020
22 min read
Topic Review: Anti-Aging
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INTRODUCTION
Is anti-aging hype or science?
Aging is a universal part of life for all of us. Because of that, the market for ‘anti-aging’ compounds and products is huge. Over the years, a host of companies and sellers claim miracle benefits on products that seek to slow down or even reverse the aging process.
In 2017 for example, a US-based startup started selling young blood transfusions ($8k per litre of blood) on the back of some initial science published in 2005 showing some promise in mice. But like for so many anti-ageing claims, the science was cherry picked and misinterpreted. “Not only is it incorrect, it’s dangerous” said the scientist who did the original study.
Beyond the pseudo-science, there is solid science on aging and even anti-aging, but it’s hard to know what to believe, particularly in the beauty business. Trying to look youthful has given rise to a $53billion market for ‘anti-aging’ focused skin-care products. For decades, lifestyle magazines have been flush with articles claiming they know the secrets about celebrity anti-aging regimes and products. But looking younger is not the same as slowing or reversing aging at the cellular level.
So what are we to make of the ‘anti-aging’ claims we hear. Is it marketing hype or real science? Will a longevity pill be developed? Is intermittent fasting anti-aging? What about skincare products – do they have evidence behind them? We asked 50 of the world’s top experts in cell biology, aging and dermatology to share the facts on anti-aging.
Here’s what we found…
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NUMBERS
Meta-Index
15,000 Age in years of the longest-lived animal on earth – the Antarctic sponge Scolymastra joubini
5062 Age in years of the longest-lived tree on earth – the Great Basin bristlecone pine found in the west of USA
122 The oldest lifespan for a human. French woman named Jeanne Calment. Although it is somewhat disputed.
30 Average human life expectancy for human pre-historic hunter-gatherers.
72 Average human life expectancy worldwide in 2016
85 Average human life expectancy in Japan
83 Average human life expectancy in Australia or Switzerland
79 Average human life expectancy in the USA
1823 Compounds listed as potential ‘anti-ageing’ agents
268% Maximum increase of average life-span from 30 different species
194% Increase in lifespan for common fruit fly from one study via herb Guduchi Churna
0 Number of studies involving humans
$53,000,000,000 Global market for ‘anti-aging’ skin care products
ORIGIN STORY
The elixir of youth: from Cleopatra to modern-day celebrities
The idea to try and slow the ageing process and become youthful has been around for millenia. Around 69 BC, Cleopatra, the Egyptian Queen apparently took donkey-milk baths. The milk held alpha-hydroxy acids filled with skin-softening properties conducive to a more youthful appearance. Some 700 donkeys were needed to provide enough milk for Cleopatra.
In the 5th century Tang Dynasty Empress Wu Zetian used carefully harvested Chinese motherwort to create a “fairy powder.” She mixed it with cold water when washing her face each morning. To this day, there are anti-aging products incorporating herbs initially used in Chinese skincare thousands of years ago.
In the 16th century with countess Elizabeth Báthory, the word’s first documented serial killer, was known for bathing in the blood of her female victims. Meanwhile Mary Queen of Scots took regular white wine baths, which were claimed to improve general complexion. Other methods used in this period included wax found in the head of sperm whales, sweet almond oil and rosewater. Today the market for anti-aging skin creams has reached $52billion. Fuelled by selfies and Instagram, there is no shortage of treatments and influencers claiming anti-aging benefits.
But anti-aging is beyond simply looking youthful but the idea of living longer. Fasting (calorific restriction) and excercise have received more scientific attention recently as ways to promote longevity and slow-down cellular aging. Potential pharmaceutical compounds have also had some scientific interest with Resveratrol, Rapamycin, Spermidine and Metformin associated with some anti-ageing benefits. But how does the science stackup?
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EXPLAINER
The Biology of Aging
All of us grew from a fertilized egg into a complex organism with trillions of specialised cells performing miraculous tasks to sustain our lives. Cells are the fundamental building blocks of our bodies, so before we begin our review, we need to define a few concepts important to how we age.
Cell division is when a cell divides into two daughter cells with the same genetic material – called mitosis. Cell division occurs when there is a need for growth and development (for example in embryos and the young) or when there is a need to replace damaged or lost cells.
Cells can be programmed to die, called apoptosis (cell suicude), which serves to eliminate worn-out, unnecessary or damaged cells. Malfunctioning apoptosis is thought to be important for the onset of age-related diseases like Alzheimer’s and Parkinson’s.
Senescence and the Hayflick limit of our cells
In 1961 researchers Leonard Hayflick and Paul Moorhead published seminal work showing that a normal human cell can only divide and replicate ~50 times before it succumbs to something called senescence.
Senescence cells stop dividing but don’t die. Over time, large numbers of old (senescent) cells can build up in tissues throughout the body. These cells remain active and can release harmful substances that may cause inflammation and damage to nearby healthy cells. Senescence may play a role in the development of cancer and other diseases.
Now known as the Hayflick Limit in biology, the limited life of human cells shattered the previous 21st century paradigm that suggested cells could replicate forever. Human cells miraculously keep a record of how many times they have been divided towards the Hayflick Limit via something called telomeres. Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces. Any time a cell divides the telomeres get shorter and the ‘aging’ clock moves forward.
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THE CONSENSUS
Are telomeres linked to longevity?
Read the full answers to this question here. In humans there are many correlative studies that show an association between short telomeres and age-linked diseases. However, all experts caution that correlations do not entail causation. Dr Gerardo Ferbeyre, anti-aging expert from the University of Montreal writes about the discovery of telomeres for longevity:
The work of Maria Blasco has provided important demonstration that telomeres are linked to aging by studying the effects of expressing telomerase in mice. Telomerase, the enzyme responsible for telomere synthesis, was discovered by Blackburn and Greider for which they were awarded with the Noble prize. In Blascos’ experiments, she and her colleagues showed that telomerase can increase the average life span in mice. However, there are important issues that remain unclear.
In humans, the most convincing evidence comes from centenarians (those that live more than 100 years) writes cell biologist Dr Vincet Geli where longer telomeres helped to sustain a healthy functioning immune system.
Do some cells in our body live forever?
Theoretically, if a cell can divide forever, then it is ‘immortal’. “Some cancer cells and stem cells can theoretically divide forever” writes cell biologist Dr Markus Schosserer. “However, they will still be constantly exposed to stress, thereby suffer damage and if repair mechanisms at some point fail, the cell will die.” So although theoretically cells in our body can live forever, it’s unlikely say the experts.
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THE CONSENSUS
Is longevity primarily determined by genetics?
Read the full answers to this question here. “No” writes geneticist Dr Janet Thornton from the European Bioinformatics Institute. “Genetics accounts for less than 30% of the effect – but it is true that longevity tends to run in families – ie some families have many very old people!”
“There is no single answer to this question, since it can be construed in different ways” writes Dr David Gems from the University College London. For individual differences in lifespan between individual people, the answer is no. But between species, genetics does have a dominant role he says in shaping overall lifespan. For example the maximum lifespan of human beings is approximately twice that of our closest relatives among the higher primates, such as chimpanzees and gorillas. This difference is because of genetics.
“The fact that longevity is so variable across species indicates a strong genetic component” writes Dr Ferbeyre from the University of Montreal. “Whether aging itself is genetically determined is still unknown” he notes. Dr Nazif Alic from the University College London adds that “The variation in longevity of individuals within a species can often be attributed to environment…However, the between species variation is mostly thought to be genetic.”
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THE CONSENSUS
Is oxidative stress the primary cause of aging?
Read the full answers to this question here. The free radical theory of aging, later termed as oxidative stress theory of aging, was the dominant paradigm in the biology of ageing writes Dr Gems from University College London. The theory suggests that aging is due to the accumulation of reactive oxygen causing oxidative damage to macromolecules (lipids, DNA, and proteins) with age.
All experts confirm this oxidation theory is not the primary cause of aging since there are 9 different hallmarks of aging known so far (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication).
“Extensive testing of the theory particularly in animals models, such as mice, fruit flies and nematodes worms has failed to support the oxidative stress theory “ writes Dr Gems. “It is near certain that oxidative damage plays a contributory role in ageing…but it is also likely that much of the oxidative damage that accumulates with age is more a consequence of the many pathologies characteristic of old age than a cause of them” he writes.
Do anti-oxidants help longevity?
There’s no evidence for that writes anti-aging expert from UNSW Sydney Dr Lindsay Wu. “At the clinical level, meta-analysis of clinical trials testing the effect of anti-oxidant supplementation showed absolutely no benefit to health, and if anything a slightly increased risk of death. However at the mechanistic level, there is good data to suggest that many of the benefits of exercise and dietary restriction in health are in fact mediated by reactive oxygen species.”
Is aging linked to inflammation?
It is very likely writes Professor Karl Riabowol from the University of Calgary since inflammation induces cell turnover resulting in senescence (aging) at the cellular level. This process is self-reinforcing in that senescent cells produces further inflammatory response via cytokines. Inflammation also correlates with various aspects of biological aging such as arthritis and other forms of autoimmunity.
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THE CONSENSUS
Is Autophagy linked to aging?
100% Affirmative via 3 experts
Read the full answers to this question here. Autophagy (“self-eating”) is a process that can induce cell death and helps a starving cell to reallocate nutrients to more critical ones from unnecessary processes. At least in animal studies, scientists know that the machinery of autophagy declines with increasing age, and that triggering autophagy can improve late-life health and lifespan.
Autophagy can break down damaged components of the cell into smaller molecules that can be used as fuel and can be stimulated by exercise and dietary restriction, two interventions that could improve longevity. By not turning over these damaged parts of the cell, defective autophagy may contribute to poor health in ageing, and there are many examples from animal studies that have established a role for autophagy in ageing.
Defective autophagy results in the accumulation of damaged proteins in the cell and is one of the hallmarks of ageing that is linked to cellular senescence. Defective autophagy also results in the accumulation of damaged mitochondria in the cells and these release reactive oxygen species which further drive senescence writes Professor of Medicine Peter Barnes from the Imperial College London
Aside from fasting, are there compounds to promote autophagy? “Spermidine, a promising anti-aging compound, was shown to induce autophagy” writes cell biologist Dr Markus Schosserer from Vienna. Foods with highest amounts of spermidine include wheat germ, soybean, green peas, rice, aged cheese and mushrooms (see this article).
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THE CONSENSUS
Is biological ageing inevitable?
67% Affirmative via 24 experts
Read the full answers to this question here. A 2017 scientific article claimed that senescence (i.e., biological aging) was not inevitable – causing much debate. We posed this question to our pool of experts. While some were open to the idea that aging wasn’t guaranteed, the majority viewed biological aging as something that can be slowed down and/or postponed but not eliminated. So it is biological ageing is likely inevitable – with a range of fascinating responses.
A number of experts did point to other immortal species like the jellyfish, Turritopsis dohrnii, which when challenged by the environment or injured can revert to its juvenile polyp phase and seemingly escape ageing writes evolutionary biologist Zac Wylde from UNSW Sydney. Immortal species suggest that aging is an evolved trait and, indeed, that natural selection may lead to slow aging, fast aging, or no aging at all, depending on ecological context.
On whether aging can be turned off in humans, “the jury is still out, but I am optimistic” writes gerontologist Dr Josh Mitteldorf from Washington University. “Exercise and weight loss extend life span. There are a few drugs and supplements that modestly extend life expectancy. The next breakthrough in human life extension is likely to be in the field of senolytics, which means the removal of senescent cells. The full conquest of aging will require hacking our epigenetic life program, altering which genes are turned on and off at which stage of life. Our understanding of epigenetics is at an early stage, but we are learning fast.” says Dr Mittledorf.
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THE CONSENSUS
Is there a limit to how old we could get?
Read the full answers to this question here. As average lifespan of humans increases across the world, the question is whether there is a hard biological limit? Experts say it is likely such a limit exists. Dr Evandro Fei Fang, an anti-aging expert from the University of Oslo writes about the upper limit:
Prof. Jon Vijg proposed a limit of 115 years of average lifespan (see Nature 2016), although it raised a lot of questions. For me, because of the DNA codes, there must be a limitation on how long we can live if we do not consider genetic editing, but just interventions by food and exercise.
Professor Lorna Harries, aging expert from the University of Exeter, is skeptical that humans will ever get beyond about 120 years of age:
Even in areas such as the blue zones (like Japan, Italy, Greece, Costa Rica, California) where people have extraordinary lifespans, people don’t live much past 120. Some people believe that extreme life extension may be possible, but personally I haven’t seen any evidence that convinces me of that at the moment.
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THE CONSENSUS
Are there ways to delay aging?
Read the full answers to this question here. All experts suggest that the most worthwhile things to do are exercising and reducing calorific intake. Professor Janet Thornton, a world-leader in biology writes:
In many organisms it has been shown that ageing can be delayed – either through genetic interventions or through dietary restriction. This goes from yeasts through worms, flies and mice up to dogs and monkeys. In particular eating less tends to increase longevity (even in monkeys).
In humans it is not ethical to perform mutations, and there are so many conflicting forces at work that it is difficult to assess the impact of dietary restrictions. In the lab in worms life span can be increased 10-fold (by a combination of mutations); in flies and mice the max increase is just 1.5 fold, but an equivalent measure is not available in humans. It is likely that the human system is complex with many interconnections and buffering, so such extensions may not be accessible.
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THE CONSENSUS
Do any ‘anti-aging’ compounds or products work?
80% Uncertain via 5 experts and 3 here.
Read the full answers to this question here or here. There have alot of research on different compounds and their potential to be ‘anti-aging’.
Several candidate anti-aging compounds do exist such as metformin and rapamycin that have been shown to extend lifespan in test organisms such as worms, flies and mice. Compounds that eliminate senescent cells from the body called senolytics may also have anti-aging properties. However, to date, no experiments have demonstrated beneficial effects in humans but these are the early days of aging research.
Professor Karl Riabowol, expert on anti-anging from University of Calgary
Other experts agree. Dr Lizzy Ostler, biogerontologist from the University of Brighton confirms that Rapamycin has been found to have anti-aging effects for animals. She notes that another closely related compound called Everolimus, has also been shown to “rejuvenate the immune” system in older people.
There is also some very promising research on “senolytic” compounds writes Dr Ostler. These are designed to selectively remove senescent cells from the body and so reduce the consequences of their inflammatory behavior – such as arthritis, cardiovascular disease and even dementias.
Finally, there is evidence that some compounds can safely rejuvenate senescent cells in vitro (changing their behaviour back to that of young cells, without making them cancerous), and this may lead to alternative therapies for age related degeneration.
But all experts say there is little evidence that anti-aging products or supplements work in humans. “I am not aware that any of these compounds work in humans” writes Professor Janet Thornton. In any case, Dr Nazif Alic, an anti-aging expert from the University College London says we should focus on other things as we age:
I think this will really depend on what you consider as “anti-aging”. If we think about health as we get older, I think that diet, metal and physical activity, and a healthy lifestyle are more important than most commonly encountered products or supplements.
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THE CONSENSUS
Is a ‘longevity pill’ possible?
Read the full answers to this question here. Experts were divided on this question – but all agree the research is still in its infancy.
There are lots of groups looking for one (that humans could use), including potential ways involving selective killing of senescent cells to remove them from the body. Drugs that would do that are called “senolytic” drugs. This has been done in genetically engineered mice [not possible in humans], and mouse lifespan was lengthened by about 20%, with improved health at a given older age.
Professor Dot Bennet from St Georges University London is wary of such a pill:
No very clear results in humans yet, although potential senolytic drugs are being tested in clinical trials for activity against diseases of ageing like knee arthritis. This might work, because senescent cells produce factors that locally promote inflammation. But I have not heard any really striking outcomes as yet. The current drugs may not be selective enough.
Others like Professor Gerardo Ferbeyre from the University of Montreal were more positive:
Yes, research in model organisms already show that multiple compounds can extend life span. For example metformin increase life span in rodents. We showed two mechanisms by which this drug may work. Frist, metformin acts on reactive oxygen species (ROS) in a unique way. It does not prevent the formation of ROS in normal cells but in senescent cells and in tumor cells it decrease their production. We think it acts as a sort of ROS buffer. Second, metformin prevent the secretion of inflammatory cytokines by senescent cells.
‘Possibly’ writes Professor Thornton but “At the moment i believe that the most practical option would be to reduce food intake – but whether lifespan extension will occur if this is only done in old age, or whether such a regime should be applied from birth, is not known.”
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QUICK ANSWERS WITH CONSENSUS
Does mortality give life meaning? Arguably. Some studies suggest mortality gives life meaning by providing structure, appreciation, and understanding, while other studies indicate that meaning in life can exist independently of mortality.
Are there species that are biologically immortal? Yes. These studies suggest that species like Turritopsis dohrnii, certain simple animals, and planarians exhibit traits of biological immortality through rejuvenation and regeneration.
Are there ways to promote cellular senescence? Yes. These studies suggest that cellular senescence can be promoted through mechanisms such as telomere shortening, epigenetic changes, DNA damage, and activation of specific tumor suppressor pathways.
TOP ANSWER
Do any ‘anti-aging’ skincare claims have validity?
Desmond Tobin: An Professor and expert from University College Dublin in Dermatology
Uncertain. The quality of skin care interventions can be hugely variable; from those containing no ‘bio-available’ active ingredients to those that may have significant (and even technologically-advanced) power.
It is important to note that the vast bulk of skin aging is due to unprotected sun exposure, so limiting this by using sunscreen skincare will provide ‘anti-aging’ protection for the skin. Other skin care products many contain active ingredients to boost the synthesis of skin structural proteins like collagen, fibrillin etc. or to reduce age-related pigmentation spots, although these may be at too low a concentration in skincare products to make a detectable difference..
So, the advice is to check the ingredient lists, see if companies have been ‘brave enough’ to carry out laboratory & clinical research on their ingredients/products, and even more importantly that they have been brave enough to submit these data for peer-review scrutiny in the academic literature. If they have, then they are probable worthy of your attention.
TAKEAWAYS
- Lifespans have increased dramatically in the past century but there is likely an upper limit of ~120 on how much humans can age
- Oxidation is not an important aspect to aging and anti-oxidant supplements do not promote longevity
- Good evidence that exercise and calorie restriction help extend health and longevity
- Pharmaceutical compounds exist that extend life in animal models, but for humans there is no evidence yet
- Senolytic compounds eliminate senescent cells and hold promise, but much more research needs to be done
- ‘Anti-aging’ in skincare is misleading since no ingredient slows or reverses the aging process.
- The vast bulk of skin aging is due to unprotected sun exposure, so wear sunscreen. And always check the active ingredients and see if they have submitted trials to peer-review.
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