≡ Menu

Lifelong Fitness and Ageing Conference

This past week I attended the conference: Lifelong Fitness and Ageing: Can we Monitor, Can we Treat? in Hasselt, Belgium. They invited me to come speak on Quantified Self technologies, which I was happy to do. The workshop ended up being more geared towards academic researchers than I had anticipated, but nevertheless there were some good practical tips on health and aging that I picked up. My understanding of the molecular biology of aging was certainly deepened.
It was also a great pleasure to meet Aubrey de Grey and hear him present SENS, his strategic approach to combating the diseases of old-age by tackling the most fundamental processes driving aging. He is one of the most idealistic and determined people that I have ever met. That combination has been present in the greatest movers and shakers in history, and I think he fits the mold well. He has made his life into a crusade against aging, and I don’t think he will stop at anything to see it vanquished.
Unlike my previous summary of the Wearable Technologies Europe 2013, this writeup will not be a full summary, but will only highlight that knowledge which seems most useful to the individual in combating aging. Apologies to the speakers whose excellent talks I have omitted.

Air pollution and population susceptibilities: from epidemiology to molecular mechanisms of ageing – Tim Nawrot

There’s rather strong evidence that particulate air pollution at levels common in our cities is harming our health. The evidence begins with epidemiology: large US cohort studies indicate air pollution correlates with cardiovascular mortality [4] and shorter mean leukocyte telomere length. Early life exposure to pollution seems to be disproportionately impactful. Smoking bans result in improvements in cardiovascular mortality, even in the nonsmokers in a city [9]. Lung organ transplant is more successful in those living in the country as compared to in cities.
Causality and mechanisms for the above have been well understood by RCTs in mice and rats. They cause systemic (starts in lungs but spreads) oxidation and inflammatory effects. The atherosclerotic effects occur because very small ( ~ 2.5 μm) particles are able to enter the blood from the lungs, where they provoke an inflammatory immune response, which exacerbates the pathology of oxLDL leading to plaque formation.
What are safe levels? I’m not aware of any health benefits to having non-zero levels of particulate pollution, but even if there were some, it’s unlikely that levels in cities are ever low enough to be optimal. Currently, different organizations have different standards for acceptable levels of particulate pollution. For particles  ≤ 2.5 μm in size, standards range from about 10 − 25 μg ⁄ m3 for average daily exposure to severe thresholds not to exceed 25 − 35 μg ⁄ m3 within one day, depending on the advising group [3, 2, 1].
Where to find current levels? US, Europe, China.
Preventative measures: Checking the pollution level on a day, and perhaps exercising inside, depending on levels, is one basic tactic. But we will obviously be stuck with some exposure until we really start powering ourselves with green energy. If you live somewhere with very poor air quality, or are just concerned about this risk factor, you might want to consider donning a protective mask on occasion. They are inexpensive.

Telomeres as a biological clock of human aging: time to change the metaphor – Dr. Abraham Aviv

The differences in telomere length (TL) between humans are mostly due to differences at birth, secondarily due to differences in shortening rates during our growth years, and only mildly influenced by differences in shortening rates after growth has finished. TL is highly heritable, and counter-intuitively, the TL of most men’s sperm cells increases with the age of the man, partially explained by the fact that telomerase is active in male germ-line cells. It’s been proven in breeding experiments of lab organisms that selectively using sperm from fathers as they age produces offspring with longer telomeres, and that this effect can accumulate generation-upon-generation.
Dr. Aviv agreed with some of the findings in my review of telomere science, such as that the rate of TL loss in a given organism and cell type (such as in leukocytes, the most studied one) is nearly synchronous to that in most other tissues in the same organism (save rapidly-dividing cell lines like skin, hair, germline, etc). Therefore, repeated measurements of any of these tissues in an individual over time could be used to infer a TL shortening rate.
It’s a fact that TL has great predictive capacity for atherosclerosis and heart disease. Dr. Aviv also believes that the existing evidence is sufficient to make it probable that TL is not just a biomarker for aging, but is a cause of these diseases. He cited what we know about the inflammatory processes that play a role in atherosclerotic plaque development necessitating greater hematopoietic stem cell differentiation for repair. This process is sensitive to division limitations imposed by too short telomeres.
Dr. Aviv expressed doubt that any of the trials or epidemiology on mid-life practices to reduce rates of shortening of telomeres are very convincing towards the primary objectives of benefiting healthspan and/or lifespan. As I mentioned in my article, there is RCT evidence in humans that interventions such as omega-3 supplementation, meditation, qigong, and some extracts of Astragalus have been effective in humans over months or years at reducing TL attrition. However, this evidence is preliminary, in that it hasn’t been independently replicated. If you aren’t already familiar with the poor replicability of major biomedical research, then you should familiarize yourself with it now:

There’s reason to believe that most scientific studies reporting significant effects that have not yet been independently confirmed are in fact false [8][7].


Ageing, stem cells, and regeneration – Dr. Karen Smeets

Although his talk didn’t contain actionable information, it was so cool that I must say a few words about it. Planaria are worms that can totally regenerate themselves. I.e. cut one into many pieces and each piece will grow into a fully functional organism. Scientists subjected these worms to removal of some of their dopaminergic neurons from their brains, inducing Parkinson’s-like symptoms. However, the worms regenerated them, and cured themselves. One important difference that regenerative processes have as compared to the uncontrolled division in cancer is that the former obeys stopping signals, and must also follow nuanced cell differentiation signals. The worms that can regenerate don’t develop tumors very often. Needless to say, the potential for harnessing the regenerative pathways in the worm towards human health is very exciting stuff, seemingly out of science fiction. I don’t see why it shouldn’t be possible in principle, but it’s probably not something we will see tomorrow.
Humans do have some (far more limited) regenerative capacities, relying on our stem cell reserves to differentiate and replace dead or damaged cells. But this pathway can become dysfunctional in several different ways as aging plays out.

Wearable smart systems for personal healthcare and lifestyle – Dr. Ruud Vullers

Imec is an independent, nonprofit Flanders-based research organization. They are producing exciting breakthroughs in Quantified Self technologies, which I also mentioned in the Wearable Technologies Europe 2013 summary. Here some glimpses of future technologies were presented:
  • ECG patch – Low power, non-bulky, sticks on, bluetooth, can be worn for the entire day.
  • EEG – Wireless, dry electrodes, active electrodes, low-noise, low power. They imagine improvements to driving and equipment operation by monitoring drowsiness levels. E-learning that adapts to concentration. Prediction of epilepsy.
  • Patch – They have a heart-patch that combined with an accelerometer is >90% accurate for metabolic rate, and that they compared vs the best proper caloric burn tracking.
  • Stress monitoring – Bracelet for skin conductance, 3D accel, skin temp, skin humidity, ambient temperature, ambient humidity. Seems like a competitor for the Basis band.
  • Pollution – Idea is that you can measure atmosphere through your mobile phone. They want to crowdsource this to go from a body area network to a personal area network.


Ways to enhance health and life: what model systems of ageing can teach us – Dr. Adam Antebi

Life expectancy has increased nearly linearly in the developed world for the last 150y or so. It’s not stopping just yet. However, maximum lifespan has been capped at about 120y, so the former is bound to stop unless the latter can be extended.
You may have heard about experiments successfully demonstrating life extension in model organisms such as the worm C. elegans, the fruit fly Drosophila, and the lab mouse. Almost all of these successes rely on exploiting variations of the same basic metabolic pathways that activate in response to famine or other nutrient shortage. The gold standard mechanism that is probably the most natural environmentally triggered one is food scarcity, usually called caloric restriction (CR) when imposed chronically as a treatment in scientific trials. Although there are many seemingly different individual genetic manipulations, suppressions, and activations that extend life in these model organisms, they are not additive, since most of them just promote this same pathway in different ways.
IGF – The insulin-like growth factors are two molecules (IGF-1 and IGF-2) that are important in signaling growth to occur, and CR alters IGF signaling. Reduced IGF signaling is believed to be an important mechanism by which CR, protein restriction, and intermittent fasting work to promote longer lifespan and healthspan. Reducing the effective signaling of IGF pathways either by reducing receptors and/or signaling molecules can have similar life-extending effects to CR in model organisms. One gene that presents some evidence for doing this in humans is the FOXO3A gene in humans (8 ind epidemiological studies correlating it with longevity), which 23andMe reports. In models of neurodegeneration, limiting IGF signaling can even have benefits for Alzheimer’s. It’s not totally clear that lower IGF per se is favorable for longer life. Very low IGF-1 is associated with increased diabetes and heart disease. On the other hand, Laron sydrome sufferers have very, very low IGF-1 and seem to be immune from diabetes and cancer.
The growth-reproduction see-saw: One thing that I think is massively obfuscated in the health and fitness blogosphere is that there appear to be strong tradeoffs between robust, high-performance living and longevity. Case-in-point: research presented in this talk saw a huge gain in longevity in C. elegans when they ablated (vaporized with a laser) the germline (reproductive cells) of the worms. Some epidemiology was also mentioned observing that Korean eunuchs live longer than lifestyle-matched Koreans.
As I mentioned above, there’s evidence that pathologically reduced levels of IGF found in Laron syndrome can be incredibly protective from cancer and diabetes. Yet spiking IGF levels via concurrent consumption of fast-digesting carbohydrates and protein is a principle strategy of those looking to gain muscle mass. That might be a dangerous game to play.
TOR – The TOR pathway (mTOR in mammals) is one of the metabolic pathways that is very well-conserved across different organisms, making findings in model organisms more likely to be relevant to humans. Mild suppression of TOR is associated with lifespan increases, and is probably why rapamycin has been an effective mimetic of CR, proven to slow aging in mice. Other mTOR inhibitors in vitro include epigallocatechin gallate (EGCG), caffeine, curcumin, and resveratrol, but I’m unaware of evidence showing that they are effective in vivo, when taken as supplements.

Regenerative medicine: a route to true preventative geriatrics – Dr. Aubrey de Grey (SENS Research Foundation)

Metabolism in all its forms causes intermediate biomolecular damage, which in turn causes macro-pathologies like heart disease, joint stiffening, cancer, etc. Although the intermediate damage accumulates throughout our lifetimes, it doesn’t seem to cause macro-pathologies until certain critical tipping points are reached. But after those points, then pathologies can build in severity very rapidly.
One of the themes of this workshop was that when people discuss aging, they are often talking past one another, because they have different definitions of what aging is. Aubrey’s definition:

“Aging is the set of processes that progressively reduce the time before the individual is likely to suffer a permanent loss of physical or mental capacity.” [13]

He defines death from aging as all deaths due to causes that primarily affect old people. By this definition, 100k of the 150k people who die per day die of aging. In the developed world, >90% die from aging. He stressed the importance of this logical point: If you are for eradication of the named diseases that people die from, such as heart disease, cancer, pathogenic infections, etc, then logically you should be for the eradication or at least amelioration of aging, since remediating the damage caused by aging would be effective at reducing all of those diseases and the deaths due to them.
Aubrey also provided some facts about how we currently spend our resources fighting the diseases of old age: After age 60, the average care given in the last-year-of-life of an individual than the cumulative care given up to that point in life. We should question whether that is really a good use of our medical funds.
We currently treat and study aging in 2 subfields:
  • Gerontology – Slow down aging by slowing the creation of the intermediate biomolecular damage.
  • Geriatrics – Ameliorate and manage the pathologies resulting from biomolecular damage.
Aubrey’s opinion is that gerontology has completely failed, and that failure is due to the complexity of metabolic pathways – basically it’s totally implausible to modify metabolism w/o unintended side effects, many if not most of which would probably be adverse side effects. He offers another path forward, through SENS:
  • Regenerative medicine – Interventions that restore structures of tissues and organs to undamaged states.
He sees regenerative medicine as acting at an intermediate location as compared to gerontology and geriatrics, acting directly on the damage itself to repair it, much like how those who like to keep old cars running while driving them regularly take them to the mechanic often enough to fix damage caused by use.
SENS is currently working on/funding research to:
  • Enable the body to dispose of oxLDL better – Which could remediate atherosclerosis and massively improve outcomes for heart disease.
  • Prevent macular degeneration – A2E is the problem molecule, since it builds over time and is undegradable by the body. Can reach 20% of mass of eye cells with old age.
  • Mitochondrial DNA – Aubrey says that mitochondrial DNA mutations can’t definitively be implicated as a fundamental cause of aging. He thinks there’s enough circumstantial evidence though to strongly suspect it. Mitochondrial DNA only codes for 13 proteins. The plan is to make mutant mtDNA harmless via allotopic expression, i.e. expressing these genes in the nucleus, which is far more protected from mutations than the mitochondria. The trick will then be getting the mRNA or proteins to the mitochondria where they are needed.
Aubrey believes that they are far enough along with some of SENS’s objectives to implement in mice within 10y, and within 25y in humans. He sees the potential for middle-aged humans to get 30y of extra life at that point.

Vitality and aging – Dr. Frans van der Ouderaa

This talk focused on the clinical research surrounding aging and the diseases of old age. It was divided into a component on epidemiology and on intervention trials.

Epidemiological studies

Some of the big human epi-studies are: Framingham (oldest and longest), EPIC-UK, Leiden Lang Leven, Rotterdam, Honolulu, Physicians Health, Nurses Health, New England, Midus, LASA, Whitehall.
  • Over the last 170y, we have seen an increase on avg of 6 hours in average lifespan per day of time (includes child mortality).
  • In the developed world from 2000 to 2010 the chance of a 65 year old living to reach 90 went from 10%/25% to 20%/34% for men/women.
  • Blood pressure and (pre)diabetes are two of the biggest predictors of mortality and quality lifespan.
  • It seems that the common lifestyle factors stack in terms of benefit – e.g. activity, fruit and veg cons, nonsmoking, social connectedness/support.
  • As a society, we probably haven’t paid sufficient attention to the robust epidemiological findings on good social connectivity/support as a predictor of health and longevity. It has about as much explanatory power for longevity as the strongest lifestyle choice (smoking). A study within the UK civil service revealed that higher status jobs correlated favorably with longer lifespan. The HPA axis and cortisol show up as potential explanators of these findings.
  • Polymeal – a meal based on data-mining dietary findings that correlated with longevity and health. Nice diet if you ask me 😀
    • 150 mL/d of red wine (about one glass)
    • 100 g/d of dark chocolate
    • 400 g/d of fruits and vegetables
    • 2.7 g/d of garlic
    • 68 g/d of almonds
    • 118 g of fish four times per week.
  • The ApoE gene is the gene whose (common) variants best predict longevity (23andMe measures it).


Diabetes Prevention Study (Finland) [10]The population was Finnish prediabetics. Lifestyle counseling suggesting diet lowish in fat, low sat fat, higher fiber, and a lifestyle of higher exercise/activity. Diabetes development eventually dropped to 58% as compared to controls after 6 years. The cohort that adopted 4 or 5 of the 5 suggested lifestyle changes nearly had zero diabetes. Weight change was very correlated with good outcomes.
Diabetes Prevention Program (DPP) (US) [6] – A prediabetic group that was coached towards lifestyle changes involving more activity. Compared to a metformin intervention (the most effective pharmaceutical for diabetes), the lifestyle intervention did better.
Dr. van der Ouderaa believes that future dietary experiments should move towards better monitoring of diet and activity using technology. I think this is right on.

My Takeaways

Caution is warranted regarding indiscriminately increasing one’s antioxidant capacities – Trying to re-engineer your oxidation/reduction pathways, by e.g. decreasing oxidation with large, diverse, and chronic antioxidant consumption is probably not a wise game to play. Oxidation in the body serves many important signaling roles embedded in very complex signaling networks. Trying to re-engineer this system better for health and longevity seems about as wise as tinkering with your hormones.
Maybe it makes sense to try to target normal youthful levels of antioxidant capabilities and hormone levels, but if you exit these bounds you are probably going to cause at least some undesirable ripple effects elsewhere in the network. Furthermore, antioxidant supplementation trials and epidemiology in humans by-and-large have returned null or even some deleterious findings for antioxidant supplementation and the endpoints of heart disease and total mortality [12]. Antioxidants can also block many of the beneficial adaptive changes caused by exercise, such as increased insulin sensitivity [11].
Done with overeating: I’ve been drifting in this direction for awhile now, but I think I’ve finally decided to stop eating beyond-full. I started force-feeding myself about a year ago as an experiment to see what it would take for me to put on some muscle mass, and I eventually had some limited success with that. But I think this is too risky of a game to be playing for those of us interested in living a long time. Different threads of evidence suggest to me (note: I haven’t conducted a rigorous review, but [5]) that energy overload in and of itself (i.e. independent of food quality, glycemic load, protein, etc) is a principle mechanism for causing metabolic dysfunction and insulin resistance. The value in avoiding that outcome is hard to overstate for both healthspan and lifespan. One also should suspect that high carb/protein consumption to be a cancer risk via growth hormone and IGF elevation. Although it’s feasible that we might have gene therapeutic or other techniques to overcome these problems by the time they would likely be an issue for me, I still don’t think it’s worth the risk.
What is the current state of gene therapy in humans? I was hoping that this would be addressed in the workshop, but there was little on it. I used to hear about this in the press some years ago, but have heard almost nothing of late. I’ll take a look into it in a future post.
Keep an eye on [and even actively help] the SENS program – To my non-expert brain, SENS has the only plausible all-encompassing plan for massive enhancements to human longevity. Given that a call for attacks on SENS was commissioned with $20k reward, and subsequently a panel of independent experts judged that none of the three submissions had demonstrated that the plan was implausible, it makes sense that we as a society would donate at least a small fraction of the resources that we put towards disease-prevention research to SENS. Yet that hasn’t appreciably happened. I hope that it does in the future, and to that end I have made a small donation myself. SENS is funding and carrying out some great research already, even with their small budget.

Further Information

For a video overview of SENS, see Aubrey de Gray’s TED talk, or the more recent talk. I’m currently reading his book.For a lay-friendly editorial discussing the fallibility of scientific findings that have not yet been independently confirmed, see: Freedman, David H. “Lies, damned lies, and medical science.” The Atlantic 306.4 (2010): 76-84.

More on VIB, the sponsoring organization of the workshop.

Note: Some of the links in this post are affiliate links, meaning that if you purchase through them then you help support Biohack Yourself. You will always get the same or lower price as compared to the retailer’s default price.


[1] : Air Quality Standards – Environment – European Commission. http://ec.europa.eu/environment/air/quality/standards.htm, . URL http://ec.europa.eu/environment/air/quality/standards.htm.

[2] : National Ambient Air Quality Standards (NAAQS) \textbar Air and Radiation \textbar US EPA. http://www.epa.gov/air/criteria.html, . URL http://www.epa.gov/air/criteria.html.

[3] : WHO \textbar Air quality and health. http://www.who.int/mediacentre/factsheets/fs313/en/index.html, . URL http://www.who.int/mediacentre/factsheets/fs313/en/index.html.

[4] Robert D. Brook, Sanjay Rajagopalan, C. Arden Pope, Jeffrey R. Brook, Aruni Bhatnagar, Ana V. Diez-Roux, Fernando Holguin, Yuling Hong, Russell V. Luepker, Murray A. Mittleman, Annette Peters, David Siscovick, Sidney C. Smith, Laurie Whitsel, Joel D. Kaufman: “Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association”, Circulation, pp. 2331—2378, 2010. URL http://circ.ahajournals.org/content/121/21/2331. PMID: 20458016.

[5] Andrea S. Cornford, Alexander Hinko, Rachael K. Nelson, Ariel L. Barkan, Jeffrey F. Horowitz: “Rapid development of systemic insulin resistance with overeating is not accompanied by robust changes in skeletal muscle glucose and lipid metabolism”, Applied Physiology, Nutrition, and Metabolism, pp. 1—8, 2012. URL http://www.nrcresearchpress.com/doi/abs/10.1139/apnm-2012-0266.

[6] Diabetes Prevention Program (DPP) Research Group: “The Diabetes Prevention Program (DPP): description of lifestyle intervention”, Diabetes care, pp. 2165—2171, 2002. URL http://www.ncbi.nlm.nih.gov/pubmed/12453955. PMID: 12453955.

[7] Ioannidis JA: “Contradicted and initially stronger effects in highly cited clinical research”, JAMA, pp. 218—228, 2005. URL http://dx.doi.org/10.1001/jama.294.2.218.

[8] John P. A. Ioannidis: “Why Most Published Research Findings Are False”, PLoS Medicine, 2005. URL http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/. PMID: 16060722 PMCID: PMC1182327.

[9] James M. Lightwood, Stanton A. Glantz: “Declines in Acute Myocardial Infarction After Smoke-Free Laws and Individual Risk Attributable to Secondhand Smoke”, Circulation, pp. 1373—1379, 2009. URL http://circ.ahajournals.org/content/120/14/1373. PMID: 19770392.

[10] Jaana Lindström, Anne Louheranta, Marjo Mannelin, Merja Rastas, Virpi Salminen, Johan Eriksson, Matti Uusitupa, Jaakko Tuomilehto: “The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity”, Diabetes care, pp. 3230—3236, 2003. URL http://www.ncbi.nlm.nih.gov/pubmed/14633807. PMID: 14633807.

[11] Michael Ristow, Kim Zarse, Andreas Oberbach, Nora Klöting, Marc Birringer, Michael Kiehntopf, Michael Stumvoll, C. Ronald Kahn, Matthias Blüher: “Antioxidants prevent health-promoting effects of physical exercise in humans”, Proceedings of the National Academy of Sciences, pp. 8665—8670, 2009. URL http://www.pnas.org/content/106/21/8665.

[12] Yizhou Ye, Jing Li, Zhongxiang Yuan: “Effect of Antioxidant Vitamin Supplementation on Cardiovascular Outcomes: A Meta-Analysis of Randomized Controlled Trials”, PLoS ONE, pp. e56803, 2013. URL http://dx.doi.org/10.1371/journal.pone.0056803.

[13] Aubrey D.N.J. de Grey: “The Desperate Need for a Biomedically Useful Definition of “Aging””, Rejuvenation Research, pp. 89—90, 2013. URL http://online.liebertpub.com/doi/full/10.1089/rej.2013.1428.

{ 3 comments… add one }

  • EddieO 2013/05/11, 04:58

    Hey Winslow,

    Once again a great report, thank you! On the longevity commentary I checked my 23andme SNP’s for the key markers and thought you, and your readers, may find it helpful to know which SNPs to check:

    Marker rs2764264 – the FOXO3A gene.
    A 2008 study compared 213 Japanese men who lived 95 years or longer to 402 Japanese men who died before the age of 81. The researchers found that the longer-lived Japanese men were more likely to have a C at one or both copies of rs2764264, a SNP in the FOXO3A gene. Each C at rs2764264 was associated with about 1.6 greater odds of reaching age 95 or beyond compared to having a T at this position. The FOXO3A gene has been shown to modulate longevity in laboratory animals.
    I have TT ie Typical odds of reaching age 95 or beyond.

    The APOE variants are a bit trickier but 23andme gives a decent report as part of the Alzheimer’s health report for each subscriber. SNPs determine three APOE variants? Variant rs429358 rs7412
    ε2 = T + T
    ε3 = T + C
    ε4 = C + C
    Since the fourth combination—rs429358(C) + rs7412(T)—has never been observed, we can determine APOE variant status clearly from these two SNPs. For example, people with the CT genotype at both SNPs must be ε2/ε4, and people with CT at rs429358 and CC at rs7412 must be ε3/ε4. In addition, we can determine APOE variant status to varying degrees even if an individual has no data at one of the two SNPs. People with the TT genotype at rs7412 must be ε2/ε2 even if they have no data for rs429358. For people who have genotype data at rs429358 but no data for rs7412, we can determine how many copies of ε4 must be present, although we cannot always determine the exact variant combination.

    Happily I am in credit in this area. 4.9% chance where the average risk is 7.5%.

    Another Marker related to genetic longevity is rs2542052: 23andme cite a study comparing 213 Ashkenazi Jewish subjects ranging in age from 95 to 107 to a group of counterparts about 30 years their junior. Members of the longer-lived group were more likely to have a C in both copies of the SNP rs2542052. People with this genetic signature tended to be more sensitive to insulin and were less likely to have high blood pressure, which suggests it may promote longevity by protecting against cardiovascular disease.
    I was CC ie happily higher odds of living to 100! :)

  • college campus 2020/01/19, 12:42

    I like writing textual essays (such as blog posts!).

Leave a Comment