In the same way I find it crucial to mention progress in aging research and the possibility (no matter how distant and difficult) of curing aging, it is equally important to fight false publicity, particularly in a field with such a fraudulent past like aging research. Products that claim to cure or reverse aging mislead the public and impact on the reputation of those doing serious work. Here I review some of the available products aimed at the aging process and the misconceptions in which most are based.
Key words: ageing, anti-oxidants, antiaging, elderly, eternal youth, immortalism, immortality, life span, old age, rejuvenation, science, telomeres
I will be clear from the start: presently, there is no proven way to delay, even if slightly, the human aging process (Olshansky et al., 2002; Hayflick, 2004). Although companies, and often journalists and admittedly scientists too, like to tout whatever-anti-aging-product-is-currently-in-the-news as the "fountain of youth" or the "holy grail", the truth is we do not know of any way to even slightly delay the aging process, much less stop or reverse it (which is what the "fountain of youth" and the "holy grail" are all about). Unfortunately, understanding why a given anti-aging intervention is fantasy rather than science often requires time to gather the scientific data, which not everyone is willing to invest (Warner et al., 2005). If you are visiting this website to learn more about anti-aging science rather than find out about the latest anti-aging trends in Hollywood, then the discussion below is for you.
"Fountain of Youth" by Lucas Cranach. Reversing human aging so far remains fiction.
One can delay some of the many effects of aging. For example, if you avoid unprotected exposure to the sun, you delay skin aging. Similarly, a balanced diet can lower the incidence of heart disease. Given the complexity of aging, however, delaying the onset of a single age-related disease cannot scientifically be considered as equivalent to delaying the aging process as a whole (Hayflick, 2004). Just because a given product or lifestyle delays the onset of a particular age-related change or pathology does not mean it delays aging, in the same way that antibiotics used to treat opportunistic infections in patients with AIDS, even if they preserve health, are not targeting the ultimate cause of AIDS which is HIV.
There are also ways of living longer. Following all that motherly advice like regular exercise and adequate nutrition can make you live longer (Holloszy, 2000), and any therapy that ameliorates mortality from a specific disease will increase longevity. Still, living longer does not necessarily mean that the fundamental process of aging has been slowed down. Living a healthy life will lower your mortality across the entire lifespan, even if there is no impact on aging and age-related changes. For example, longevity increased roughly 50% in the past century and yet there is no evidence people age slower; we live longer now mostly because deaths caused by infectious diseases have gone down (Hayflick, 1994, pp. 84-88). This important distinction holds true for animal studies. Royal jelly and fish oil can significantly increase the average lifespan of mice (Jolly et al., 2001; Inoue et al., 2003), and yet that does not mean that aging has been delayed by these treatments; all it means is that these nutrients are healthy. Therefore, a great deal of care is necessary when interpreting life-extension studies and there is a lot of room for controversy of what represents delayed aging.
So how can we determine whether a given intervention delayed aging? Based on the definition of aging detailed elsewhere, a given intervention to be accepted as anti-aging must demonstrate that the onset or pace of multiple age-related changes, including pathologies, is delayed. In addition, while accurately quantifying the rate of aging is impossible, one method to estimate the rate of aging is to calculate the rate at which mortality increases with age and so determining whether a given intervention delays this rate can also help determine if the aging process was delayed (de Magalhaes et al., 2005a). Any intervention that fails to meet these criteria cannot be considered as truly anti-aging, even if it extends average lifespan or delays a given age-related change. This debate concerning what anti-aging means is the major source of confusion concerning anti-aging medicine and is often used by companies and even scientists to mislead the public. Certainly, some products pitched as anti-aging may be healthy and/or may soften the effects of aging. For example, a given anti-wrinkle cream may soften one particular effect of aging (wrinkles) but it will not impact on any other aging sign. Importantly, an anti-wrinkle cream will not increase longevity much less delay the mortality acceleration with age and so cannot be scientifically considered as anti-aging.
To complicate matters even further, because studying aging in humans is extremely expensive and time-consuming, it is virtually impossible to test whether a given intervention or product delays aging in humans and thus testing whether a product impacts on aging is usually done in animal models. Because animals may or may not be representative of human biology, interpreting the life-extending effects of products in animals must be done with caution. Even studies in animals might be artifacts of particular experimental conditions. For example, one of the largest increases in lifespan (44%) by a product was obtained by feeding worms a synthetic antioxidant called EUK-8 (Melov et al., 2000). Other scientists, however, failed to reproduce these results (Keaney and Gems, 2003), even though EUK-8 was shown to increase antioxidant levels (Keaney et al., 2004), which suggests that possibly very peculiar conditions are necessary for this particular product to increase lifespan.
As detailed elsewhere, senescence.info is not a medical website. It is a website about aging, namely about the whole aging process with a special emphasis on human aging, and thus the following products are interpreted in view of their potential impact on the human aging process as a whole. Hopefully, I can demystify some of hype surrounding these products and, based on scientific evidence, help clarify what they can and cannot do.
Caloric Restriction
The only known method that might be able to delay human aging is caloric restriction (CR). Given the large body of research on CR, and the many products trying to emulate its effects, a more detailed discussion is available elsewhere.
Hormonal Therapies
Many hormones' levels go down with age. Some of the oldest and still most popular anti-aging treatments emerged based on the assumption that hormonal changes are important in aging. The most famous of these involves human growth hormone (HGH). Growth hormone has been used as an anti-aging treatment for a long time and some evidence suggests HGH has beneficial effects in elderly people (Blackman et al., 2002): HGH supplements might increase muscle mass, strengthen the immune system, increase libido, etc. There are studies in elderly patients in which they claim to feel younger after HGH treatment. While HGH was once hailed as a major breakthrough, like many other anti-aging products, it failed to live up to expectations, in part because of its negative side-effects (Liu et al., 2007). The most serious side effect is probably cancer. Although HGH is not mutagenic, it makes cancer grow, which means that if you have a cancer and take HGH, the cancer will spread faster. Other side-effects might include weight gain, high blood pressure, diabetes, etc.
Studies in mice, however, do not by and large suggest a beneficial role for GH. If any, they suggest a harmful role. Though one study found that a low-dose GH therapy increases lifespan in aged mice (Khansari and Gustad, 1991), mice genetically modified to produce lots of GH live less than controls while mice producing less GH live longer (Coschigano et al., 2000; Laron, 2005). Of course, as mentioned above, studies in animals are not always relevant to human biology. Nonetheless, the results in mice suggest that higher GH levels will not make you live longer. The humans studies also suggest a sort of supernova effect: HGH makes you feel great but might actually diminish your lifespan. In conclusion, HGH might be useful in certain cases of depressed aged patients but otherwise should be seen as cocaine for granddad. Lastly, I should point out that there are (young) patients with GH deficiency that if untreated have a reduced longevity (Besson et al., 2003), so HGH does have clinical applications.
Insulin-like growth factor 1 (IGF-1) is another hormone that may play a role in aging and can be purchased as a dietary supplement. Like GH, IGF-1's levels decline with age and, in mice, low levels of IGF-1 appear to correlate with longevity; mutations in mice that lower IGF-1 seem to extend lifespan, as mentioned elsewhere. So, just like for HGH, IGF-1 injections could be counter-productive. In fact, there is some evidence that little people with low levels of IGF-1 live longer (Krzisnik et al., 1999). Interestingly, anti-aging therapies based on lowering IGF-1 may be possible (Miller, 2005). The idea would be to develop a therapy that could diminish the levels of IGF-1. As mentioned elsewhere, IGF-1 does appear to play a role in aging, but whether it can be used in anti-aging is pure speculation at this stage. Clearly, however, IGF-1 injections are unlikely to extend lifespan and may even be harmful.
Other hormones whose production decreases with age include DHEA and melatonin. DHEA has been reported to improve the well being of the elderly by a variety of ways: improved memory, immune system, muscle mass, sexual appetite, and benefits to the skin. Protection against cancer has also been argued but some types of cancer--namely prostate and breast cancer--actually appear to increase with DHEA. Minor side effects such as acne have also been reported.
Melatonin is a hormone mostly involved in sleep and circadian rhythms, the latter hypothesized by some to be associated with aging and life-extension (Froy and Miskin, 2007; Kondratov, 2007). It appears to have antioxidant functions--more about antioxidants below--in the brain and may have some beneficial effects in elderly patients in particular in terms of sleep (Poeggeler, 2005). Some of its proponents claim it delays the aging process and many age-related diseases, though this is far from proven. In mice, melatonin can increase lifespan but also appears to increase cancer incidence (Anisimov et al., 2001). In humans there is no data to even conclude that melatonin extends longevity (Karasek, 2004). Although it can be used for jet lag and some sleep disorders, it may also cause sleep disorders such as nightmares and vivid dreams. Recently, a study claimed that melatonin levels do not decrease with age, except maybe at night, although due to diseases or drugs elderly persons can have low levels of melatonin (Zhao et al., 2002). Melatonin may also aggravate asthma.
Finally, for women, estrogen is a popular anti-aging therapy. This hormone is generally used in conjunction with others in hormone replacement therapy. It does reduce the effects of menopause protecting against heart disease and osteoporosis. I've read of weight gain and thrombosis as side effects and I've read that it should not be taken for long periods--i.e., several years.
Antioxidants
One theory of aging is the free radical theory of aging. Succinctly, when oxygen is used to make energy in human cells, it releases reactive compounds called free radicals or reactive oxygen species (ROS). To fight ROS, cells possess an array of defenses called antioxidants many of which can be synthesized or extracted, purified, and then sold, generally in tablets, as anti-aging drugs (Ames et al., 1993). Common antioxidants include vitamins A, C, and E and co-enzyme Q10. Fortunately, there is probably little if nothing wrong with taking these products as serious side-effects have not been described. Unfortunately, there is little evidence any of these products actually work. In mice, for instance, many studies indicate that antioxidants do not slow aging although they can slightly increase longevity (Harman, 1968; Comfort et al., 1971; Heidrick et al., 1984; Holloszy, 1998; Saito et al., 1998). Resveratrol, which is discussed in more detail elsewhere, and other red wine constituents can also act as antioxidants (Pervaiz, 2003) and might be protective agents of brain aging (Tredici et al., 1999; Bastianetto and Quirion, 2002; Mokni et al., 2007). So antioxidants might be healthy in the same way vitamin supplements, often including antioxidants, are healthy. There is no proof, however, that antioxidants delay aging and one study even reported that antioxidant supplements may actually increase mortality (Bjelakovic et al., 2007).
Since one major source of ROS are mitochondria, a similar class of compounds are aimed at quenching ROS production in mitochondria. These can include not only antioxidants but products that allegedly "rejuvenate" mitochondria by optimizing metabolism or membrane potential. Like for many other products, however, none of these products has been proven to have any effect on aging, either in animal models or in humans.
ALT-711
ALT-711 is one of the latest anti-aging compounds to receive worldwide attention. It acts by catalytically breaking AGE crosslinks: Advanced Glycosylation End-product crosslinks occur when glucose is attached to a protein, like it can happen in arteries. For this, ALT-711 seems to be useful against heart disease by reducing pulse pressure and improving arterial elasticity. The full effects and side-effects of this drug are still unknown but it seems like a promising intervention to ameliorate aging's effects, though it probably does not delay aging as a whole.
Future Therapies
Telomerase is an enzyme that, at least in some cell lines, appears to overcome cellular senescence--for more details please see another essay. Some have reasoned that if telomerase can avoid aging in cells, maybe it can avoid human aging too (Fossel, 1996). There are now serious efforts to develop telomerase-based therapies to fight aging and at least one product, a telomerase activator called TA-65, is already available. Personally, and even though our knowledge of telomerase is in its infancy, I am skeptical such therapies will succeed (de Magalhaes and Toussaint, 2004a). Firstly, as detailed elsewhere, mice expressing lots of telomerase do not live longer. Moreover, telomerase is important in cellular proliferation but many of our organs, such as the brain, are mostly composed of cells that do not proliferate. Hence, telomerase will do little to alleviate aging in these tissues. Lastly, there is some evidence telomerase favors tumorigenesis and so telomerase-based therapies may foster cancer. Although research on telomerase is still in an early age, I have doubts about the efficiency and long-term safety of telomerase-based anti-aging therapies.
One gene that appears to influence aging in mice is klotho. As detailed elsewhere, high levels of klotho increase lifespan by about 30%, though it is not entirely clear if aging is delayed, and low levels appear to foster aging (Kuro-o et al., 1997). Human longevity has also been linked to allelic variants in this gene (Arking et al., 2002). Its functions are still largely a mystery but since the gene encodes one secreted form that acts as a hormone, it could be synthesized and presented as an anti-aging therapy. For now, however, we will just have to wait and see. There are many other aging-associated genes that hold promise of pharmaceutical intervention, and progress has been made in finding chemicals that can modulate specific aging-associated genes and thus extend lifespan (Ja et al., 2007), as also debated elsewhere. On average, however, it takes 12 years from discovery of molecular mechanisms to develop a drug, plus 10 years of tests to make a drug available. In the case of aging the timescale may be longer, though many companies trying to develop anti-aging products are focusing on specific age-related diseases as a way to overcome the legal barriers of a product targeting aging.
Conclusions
One question you may ask me is whether I take any of these so-called "anti-aging products." The answer is no. I don't see any evidence that any of these products actually work. Besides, the aforementioned antioxidants and fish oil are good examples of the old idea that it is possible to purify the components of healthy foods to avoid having to eat them. So far, however, there is no evidence to suggest that these dietary supplements are an adequate replacement for a balanced diet, as pointed out by many others (Bjelakovic et al., 2007).
Overall, I do try to take some care of my health--like I think everyone should--by practicing regular exercise, not smoking, avoiding alcohol, and having a moderately balanced diet. My diet is not extremely healthy and so I do take dietary supplements once in a while. Namely, I sometimes take vitamins and I used to take omega-3 fatty acids since I didn't eat a lot of fish (but that has changed now). Anyway, that's as far as I go. I'm not like that married couple who didn't drink alcohol, didn't smoke, didn't eat meat, and even their children were adopted!
| No, I am not under caloric restriction and I am not a vegetarian. |  |
Disclaimer: The information on this page is for informational purposes only and should not be used as medical advice. If you wish to undergo any of these treatments or take any of the products described in this page, you should talk to your physician. I often make generalizations that might not apply to your particular medical history. As with senescence.info, use this information at your own risk.
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Copyright © 1997 - 2001, 2004, 2005, 2007, 2008 by João Pedro de Magalhães, Integrative Genomics of Ageing Group. All rights reserved.