Latitude and cancer rates in US states: Aaron Blaisdell’s intuition confirmed

In the comments section of my previous post on cancer rates in the US states () my friend Aaron Blaisdell noted that: …comparing states that are roughly comparable in terms of number of seniors per 1000 individuals, latitude appears to have the largest effect on rates of cancer.

Good point, so I collected data on the latitudes of US states, built a more complex model (with several multivariate controls), and analyzed it with WarpPLS 4.0 ().

The coefficient of association for the effect of latitude on cancer rates (path coefficient) turned out to be 0.35. Its P value was lower than 0.001, meaning that the probability that this is a false positive is less than a tenth of a percent, or that we can be 99.9 percent confident that this is not a false positive.

This was calculated controlling for the: (a) proportion of seniors in the population (population age); (b) proportion of obese individuals in the population (obesity rates); and (c) the possible moderating effect of latitude on the effect of population age on cancer rates. The graph below shows this multivariate-adjusted association.



What is cool about a multivariate analysis is that you can control for certain effects. For example, since we are controlling for proportion of seniors in the population (population age), the fact that we have a state with a very low proportion of seniors (Alaska) does not tilt the effect toward that outlier as much as it would if we had not controlled for the proportion of seniors. This is a mathematical property that is difficult to grasp, but that makes multivariate adjustment such a powerful technique.

I should note that the 99.9 percent confidence mentioned above refers to the coefficient of association. That is, we are quite confident that the coefficient of association is not zero; that is it. The P value does not support the hypothesized direction of causality (latitude -> cancer) or exclude the possibility of a major confounder causing the effect.

Nonetheless, among the newest features of WarpPLS 4.0 (still a beta version) are several causality assessment coefficients: path-correlation signs, R-squared contributions, path-correlation ratios, path-correlation differences, Warp2 bivariate causal direction ratios, Warp2 bivariate causal direction differences, Warp3 bivariate causal direction ratios, and Warp3 bivariate causal direction differences. Without going into a lot of technical detail, which you can get from the User Manual () without even having to install the software, I can tell you that all of these causality assessment coefficients support the hypothesized direction of causality.

Also, while we cannot exclude the possibility of a major confounder causing the effect, we included two possible confounders in the analysis and controlled for their effects. They were the proportion of seniors in the population (population age) and the proportion of obese individuals in the population (obesity rates).

Having said all of the above, I should also say that the effect is similar in magnitude to the effect of population age on cancer rates, which I discussed in the previous post linked above. That is, it is not the type of effect that would be clearly noticeable in a person’s normal life.

Sunlight exposure? Maybe.

We do know that our body naturally produces as much as 10,000 IU of vitamin D based on a few minutes of sun exposure when the sun is high (). Getting that much vitamin D from dietary sources is very difficult, even after “fortification”.

Aging and cancer: The importance of taking a hard look at the numbers

The table below is from a study by Hayat and colleagues (). It illustrates one common trend regarding cancer – it increases dramatically in incidence among those who are older. With some exceptions, such as Hodgkin's lymphoma, there is a significant increase in risk particularly after 50 years of age.



So I decided to get state data from the US Census web site (), on the percentage of seniors (age 65 or older) by state and cancer diagnoses per 1,000 people. I was able to get some recent data, for 2011.

I analyzed the data with WarpPLS (version 4.0 has been just released: ), generating the types of coefficients that would normally be reported by researchers who wanted to make an effect appear very strong.

In this case, the effect would be essentially of population aging on cancer incidence (assessed indirectly), summarized in the graph below. The graph was generated by WarpPLS. The scales are standardized, and so are the coefficients of association in the two segments shown. As you can see, the coefficients of association increase as we move along the horizontal scale, because this is a nonlinear relationship. The overall coefficient of association, which is a weighted average of the two betas shown, is 0.84. The probability that this is a false positive is less than 1 percent.



A beta coefficient of 0.84 essentially means that a 1 standard deviation variation in the percentage of seniors in a state is associated with an overall 84 percent increase in cancer diagnoses, taking the standardized unit of the number of cancer diagnoses as the baseline. This sounds very strong and would usually be presented as an enormous effect. Since the standard deviation for the percentage of seniors in various states is 1.67, one could say that for each 1.67 increment in the percentage of seniors in a state the number of cancer diagnoses goes up by 84 percent.

Effects expressed in percentages can sometimes give a very misleading picture. For example, let us consider an increase in mortality due to a disease from 1 to 2 cases for each 1 million people. This essentially is a 100 percent increase! Moreover, the closer the baseline is from zero, the more impressive the effect becomes, since the percentage increase is calculated by dividing the increment by the baseline number. As the baseline number approaches zero, the percentage increase from the baseline approaches infinity.

Now let us take a look at the graph below, also generated by WarpPLS. Here the scales are unstandardized, which means that they refer to the original measures in their respective original scales. (Standardization makes the variables dimensionless, which is sometimes useful when the original measurement scales are not comparable – e.g., dollars vs. meters.) As you can see here, the number of cancer diagnoses per 1,000 people goes from a low of 3.74 in Utah to a high of 6.64 in Maine.



One may be tempted to explain the increase in cancer diagnoses that we see on this graph based on various factors (e.g., lifestyle), but the percentage of seniors in a state seems like a very good and reasonable predictor. You may say: This is very depressing. You may be even more depressed if I tell you that controlling for state obesity rates does not change this picture at all.

But look at what these numbers really mean. What we see here is an increase in cancer diagnoses per 1,000 people of less than 3. In other words, there is a minute increase of less than 3 diagnoses for each group of 1,000 people considered. It certainly feels terrible if you are one of the 3 diagnosed, but it is still a minute increase.

Also note that one of the scales, for diagnoses, refers to increments of 1 in 1,000; while the other, for seniors, refers to increments of 1 in 100. This leads to an interesting effect. If you move from Alaska to Florida you will see a significant increase in the number of seniors around, as the difference in the percentage of seniors between these two states is about 10. However, the difference in the number of cancer diagnoses will not be even close to the difference in the presence of seniors.

The situation above is very common in medical research. An effect that is fundamentally tiny is stated in such a way that the general public has the impression that the effect is enormous. Often the reason is not to promote a drug, but to attract media attention to a research group or organization.

When you look at the actual numbers, the magnitude of the effect is such that it would go unnoticed in real life. By real life I mean: John, since we moved from Alaska to Maine I have been seeing a lot more people of my age being diagnosed with cancer. An effect of the order of 3 in 1,000 would not normally be noticed in real life by someone whose immediate circle of regular acquaintances included fewer than 333 people (about 1,000 divided by 3).

But thanks to Facebook, things are changing … to be fair, the traditional news media (particularly television) tends to increase perceived effects a lot more than social media, often in a very stressful way.

Nevermind body fat; put focus on muscle with age

With all the attention given to body fat, a result of the high prevalence of obesity and type 2 diabetes, skeletal muscle is often given the back seat. Yet holding on to lean muscle mass alone, in itself, may be the most important factor in avoiding health problems above. What's often forgotten is that skeletal muscle is a metabolically active tissue that plays a critical role in consuming energy and determining metabolic rate, it's the large site for fat burning, and it's a primary site for blood glucose disposal. It's time to give muscle its due.

When you reach age 60 or older, it gets harder to keep, let alone build, muscle. The reasons are a combination of lack of energy, exercise, dietary protein, and hormones. One more is a blunted protein synthesis response that is described as anabolic resistance in aging. Left to run their course, these factors eventually bring on a decrease of muscle mass over time, or sarcopenia. The loss is also often accompanied with an increase in fat mass, or sarcopenic obesity. Sarcopenic obesity brings along with it the lack of both mobility and physical function, with compounding effects, that eventually lead to increased risk of chronic disease.

The typical recommendations for adults as they lose muscle and gain weight by nutritionists is to simply exercise at least 30 minutes three times a week, eat fewer calories, and get the recommended daily intakes of protein (0.8 g per kg). But this advice has had little to offer for guarding against the heavy toll that time has on muscle. However, in the last few hours of Experimental Biology 2012 on April 25, I was fortunate enough to meet a scientist who gave a lecture on a different approach to overcoming anabolic resistance in aging.

 Kinesiologist Stuart Phillips, a professor McMaster University, is a lifelong athlete who has participated in several sports enjoying everything from hockey, football, rugby to swimming and triathlons. "Muscle has always been near and dear to my heart (no pun) and my passion," he told me via email after the event. "I don’t compete in sports much anymore except with my wife and my three boys (13, 10, and 7), who are my stiffest competition yet! So now it's about staying healthy, active, and maintaining my muscle mass, strength, and health and high-quality protein is a big part of that."

Anabolic resistance, as Phillips defines it, "is the inability of skeletal muscle in aged persons to mount a full protein synthetic response similar to that seen in the young. In other words, older people just don’t put the protein they eat into their muscles as efficiently as young people. That means as we age that our muscles gradually begin to make less protein and so out muscle mass declines otherwise called sarcopenia." But according to Phillips, the quality of protein and how much can make all the difference for holding on to muscle with age. Specifically proteins with a higher concentration of branched-chain amino acids including leucine are key to repairing and gaining muscle with age. That means a greater reliance on animal-sourced proteins like whey protein. Plant-based sources just don't cut it because of the difference in amino acid profile. Now, there's something to think about before ever considering a completely plant-based diet.

Phillips explains, for example, that soy is an excellent high quality protein as its PDCAAS (protein-digestibility corrected amino acid score) would suggest. But whey is superior for repairing and gaining muscle, as shown in several studies (1-4). Even milk protein (containing a combination of whey and casein) is better than soy for promoting lean mass gain (2; 3).

 "Our work, and that of other research groups also, suggests that it's the high leucine content of whey protein, which is an amino acid that is highly stimulatory for muscle protein synthesis and muscle growth," Phillips told me, "that along with all of the other ‘essential' (i.e., we need to eat them because we cannot make them ourselves) amino acids are present in just the right quantities to support an optimal rate of protein accretion."

Adults at an age past 60 will also need dietary protein in amounts that exceed RDIs, Phillips adds. Consuming greater quantities of proteins high in leucine such as whey can help aging adults "'overcome' (or at least minimize)" the anabolic resistance of aging and slow sarcopenia. "I'd never say you could reverse sarcopenia, but good food choices and good high-quality proteins, along with physical activity, are a big part of slowing it down!"

Exactly how much protein per day and when to get it? According to two dose-response studies by Phillips and his colleagues (5;6) young men required 20g of quality protein to maximally stimulate muscle synthesis after exercise; older men needed approximately double the dose, 40g, to gain the same maximal stimulation. That, Phillips thinks, suggests that the young should eat at least 20g per meal and older people 40g per meal.

 This is a far cry from the typical American diet of which usually consists of about 5-6g of protein at breakfast, 10-12g at lunch, and upwards of 60g at dinner. "That’s not the best way to hang onto your muscle mass," Phillips said.

 Exercise certainly is an important factor, too. Because it increases the sensitivity to leucine in muscles, Phillips suggests that it be physical activity needs to happen every day in aging adults. "In a sense, exercise, for a short-time, 'reverses' aging! In fact, what it really does is reverses the effects of inactivity, but oftentimes aging and inactivity are one and the same! So even aged muscle, when exercised, becomes sensitive to leucine and amino acids again." 

Summing up his advice, Phillips offers four steps to keep muscle (again, a critical metabolically active tissue), important to guard against sarcopenic obesity and chronic disease:

1. "Exercise and get some form of physical activity every day"
2. "Consume protein at levels higher than the current RDA" 
3. "Consume three equal protein-containing meals throughout the day containing at least 20g to 40g of high-quality protein" -- high quality meaning proteins high in BCAAS like whey, fish, or other animal-sourced proteins; simply put, most plant-based proteins have poor concentrations of BCAAs 
4. Lastly, "it should maybe go without saying, but fruits, vegetables, and dietary fiber are also important – I like the DASH [eating plan], for example, but with more protein." -- a DASH (Dietary Approaches to Stop Hypertension" eating plan is a diet rich in low-fat, low-sodium dairy products, fish, chicken, lean meats along with a large amount of whole grains, fruits, and vegetables. 

Ultimately, the research of Phillips and his colleagues could have large implications considering that the world's population of people ages 60 and older will reach an estimated two billion people by 2050 -- all who could benefit from holding on to muscle as long as possible.  

References provided by Dr. Phillips 


1. Burd NA, Yang Y, Moore DR, Tang JE, Tarnopolsky MA and Phillips SM. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men. Br J Nutr 1-5, 2012. 
2. Hartman JW, Tang JE, Wilkinson SB, Tarnopolsky MA, Lawrence RL, Fullerton AV and Phillips SM. Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. Am J Clin Nutr 86: 373-381, 2007. 
3. Josse AR, Tang JE, Tarnopolsky MA and Phillips SM. Body composition and strength changes in women with milk and resistance exercise. Med Sci Sports Exerc 42: 1122-1130, 2010. 
4. Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA and Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 107: 987-992, 2009. 
5. Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA and Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr 89: 161-168, 2009.

6. Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA and Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr 1-9, 2012.

Depression and telomeres

Reference: Wolkowitz et al. 2011 March.

People who suffer from major depression have a higher risk of age-related illness and earlier mortality (1 &2). Researchers from University of California, San Francisco (UCSF), investigated (1) telomere length in depressed individuals versus matched controls and assessed other biological factors associated with telomere shortening.

Led by Nobel laureate Elizabeth Blackburn, Ph.D., the team of researchers published their findings in the March issue of PLos One. Their hypothesis was that not all depressed subjects would show shortened telomeres equally because of a large variance in depressive episodes over a lifetime. However, they predicted that those who suffered from depression for long durations would have shorter telomeres due to longer exposure to oxidative stress and inflammation induced by psychological stress.

The scientists recruited 18 subjects diagnosed with Major Depressive Disorder (MDD), excluding those with psychosis or bipolar histories, as well as those with Post-Traumatic Stress Disorder to eliminate confounding variables due to interferences with stress hormone regulation. Results from depressed individuals were compared to those of the matched control group.


Blood samples were taken to measure leukocyte (white blood cell) telomere length, as well as oxidative stress markers (F2-isoprostanes and vitamin C) and inflammation (IL-6). The severity of MDD was determined using the standard Hamilton Depression Rating Scale and total lifetime duration of depression was estimated using a life history method interview. The history-taking and telomere assays were performed blind to each other.

The average age (ranging 36 to 47 years) of the depressed and control subjects in the study didn’t differ significantly, nor did the sex of the subjects, ethnicity distribution, or body mass index. The subjects also did not differ significantly in current or past consumption of alcohol or nicotine, marital status, or highest educational level or socioeconomic status.
The authors reported that, across the broad range of chronic depression types, the “depressed individuals did not significantly differ from controls in leukocyte telomere lengths. However, those individuals with longer courses of major depression had significantly shorter leukocyte telomeres than controls.

Additionally, regardless of depressed status, plasma vitamin C concentrations were significantly correlated with telomere length as was F2-isoprostane levels (a marker of oxidative stress).
“Importantly, the relationship between telomere length and lifetime duration of depression was significant after age was controlled, the authors wrote.

The researchers concluded that, since telomere length is a proposed biomarker of cell aging, their findings could explain why chronically depressed individuals are at higher risk of disease and mortality.

References
1. Wolkowitz et al. Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings. PLos One. 2011 March:6(3):e17837.
2. Brown et al. Association of depression and medical illness: Does cortisol play a role? Biol Psychiatry 55:1-9.

Safe weight loss for seniors through diet and exercise

In the United States, the number of obese older adults has reached disturbing heights—now affecting approximately 20 percent of those ages 65 and older—and is only expected to rise as more Baby Boomers become senior citizens.

Weight loss through calories reduction or exercise are generally good for most people as an intervention in obesity, although the appropriateness of these methods has historically been a matter of controversy in older, obese adults.

A major concern with weight loss is the accompanying loss of lean tissue, which can accelerate existing sarcopenia (age-related loss of muscle and strength), and result in reduction of bone mineral density that could worsen frailty. This could lead to greater risk of bone fractures and broken hips. Studies have yet to provide sufficient evidence, one way or another, as to whether or not weight loss provides a true enhancement to quality of life.

In a one-year, randomized, controlled trial, researchers from Washington University School of Medicine in St. Louis evaluated independent and combined effects of weight loss and exercise in nearly 100 obese older adults with an average age of 70.

The study, published their findings in the March issue of New England Journal of Medicine, randomized subjects into one of four groups:

1. Control group – participants of which did not receive any advice to change diet or activity.

2. Diet group – prescribed a diet with a deficit of 500 to 750 Calories per day and containing 1 gram of high-quality protein per kilogram of body weight per day

3. Exercise group – prescribed a diet to maintain weight while participating in three group exercise trainings weekly, which included 90 minutes of aerobic exercises, resistance trainings, and flexibility and balance exercises.

4. Diet-exercise group – prescribed a combination of the weight management instructions and exercise trainings as described in 1 and 2.

To "even the playing field" and reduce confounding variables of vitamin D and calcium status, the researchers gave all participants supplements: approximately 1500 milligrams of calcium and 1000 IU of vitamin D per day.


Results from this carefully designed study show the "diet-exercise group" preserved more lean muscle and bone density when compared to the other groups. They gained significantly better physical function and were less frail than other groups and outperformed other groups in all measured parameters: Physical Performance Test (PPT), peak oxygen consumption (VO2pseak), and Functional Status Questionnaire (FSQ) (see graphs).

"Weight loss combined with regular exercise may be beneficial in helping obese older adults maintain their functional independence," the authors concluded.

Generally, most older, obese adults are able to safely engage in regular physical activity; however, a medical professional can determine which exercises are appropriate for an individual's specific needs. Because fitness levels vary, it's important to consult a physician prior to beginning any exercise program. Certain medical conditions, as well as medications, can also affect a person’s tolerance for exercise.

Engaging in a variety of exercises, such as aerobic exercises, resistance training, and flexibility exercises, can lead to optimal health benefits. Each is essential for healthy aging.

Aerobic Exercise

Aerobic exercise of moderate intensity, 30 minutes a day, five times per week is currently recommended for adults ages 65 and older, according to the guidelines presented by the American College Sports of Medicine (ACSM). Those who are not used to exercising can start out with a shorter duration at a lower intensity and work their way up to the recommendations.

Aerobic exercise can lead to improved cardiovascular function, better quality of sleep, improved mental health, weight loss and enhanced immune function. Suggested aerobic activities for older adults include low-impact exercises such as walking, biking, low-impact aerobics, and water activities such as swimming or water aerobics.

Resistance Training

Resistance training is essential to preserve lean muscle and bone density or even reverse previous losses. In addition to improving physical function, resistance-based exercises can also reduce risk of some medical conditions like diabetes and hypertension.

Older, obese adults should perform resistance-training exercises two times weekly. The trainings should consist of 8 to 10 different strength exercises with 8 to 12 repetitions each. Again, it's best to start out slow, with lighter weights and fewer repetitions.

There are many different types of strength training exercises and a variety of equipment that can be used, including: weight-training machines, dumbbells, resistance bands, medicine balls, weighted bars, resistance of water or even one’s own body weight.

For optimal benefits, it is best to work muscles to the point of fatigue, without overstraining, while taking enough time between workouts to allow the muscles to rest and recover.

Flexibility Exercises

Flexibility and balance are also factors important to health that decrease with age. Leading a sedentary lifestyle can cause connective tissues to weaken and joints to stiffen. Ultimately, the lack of activity affects a person's range of motion, balance and posture.

Performing stretching exercises regularly can help improve flexibility and increase freedom of movement. Every workout should begin and end with proper stretching exercises to help warm up and soothe the muscles. Stretching, along with strength exercises, can also improve balance, which can help reduce the risk of falling – particularly important for elderly individuals.

Final Word

It's never too late to begin a weight-control and exercise program. Along with a healthy diet, engaging in individually-appropriate physical activity—aerobics, resistance training, and flexibility exercises—can provide older adults with improved physical function and a variety of health benefits.

Reference

Villareal DT, Chode S, Parimi N et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med 2011;364:1218-29.

Is there a link between telomeres and dietary fiber?

New evidence published in Archives of Internal Medicine has it that eating more dietary fiber, particularly from whole grains, could lead to a longer life. The large study found a high-fiber diet reduced risk of heart disease and cancer, as well as infectious and respiratory illnesses.

This is great news for those eating diets high in fiber. What’s also interesting is that another reason why dietary fiber is protective to health is because of its influence on telomeres. Telomeres are the protective caps at the end of chromosomes, and their length is considered the closest way to measure lifespan in humans.

As reported in a prospective cohort study published in the March 2010 issue of American Journal of Clinical Nutrition (AJCN), telomere length is positively associated with higher fiber intake in women. Dietary fiber from whole grains appears to provide the strongest benefit.

In addition, in the AJCN study, the researchers found telomere length was negatively associated with increased waist circumference and higher intake of omega-6 fatty acids in the diet.

Because the study was only observational, the authors reported that further investigation is necessary to further illuminate the link between dietary fiber and telomere length.

Whole grains examples are rolled oats, buckwheat, whole wheat, and wild rice. The grains contain the entire grain kernel, which include the bran, germ and endosperm. Less than 5 percent of Americans consume the minimum recommended amount of whole grains, which is about 3 ounce-equivalents per day, according to U.S. Department of Agriculture.

Americans barely receive half the amounts of dietary fiber recommended daily. How much dietary fiber is enough? The recommended amounts are 25 grams of fiber for women and 38 grams of fiber for men.

The AJCN study was among the first to document the relationship between diet and telomere length. The authors of the study concluded that the results provided more support that an improved diet and lifestyle would indeed help to slow the aging process.

"Telomere shortening is accelerated by oxidative stress and inflammation, and diet affects both of these processes," the authors report.

Studies have also found that the following changes in diet and lifestyle are all positively associated with telomere length:

•  not smoking
• exercising regularly
• maintaining a normal body weight
• healthy management of stress
• consuming sufficient long-chain omega-3 fatty acids from fish weekly
• maintaining a healthy vitamin D status
• consuming a quality multivitamin daily
• consuming antioxidants such as CoQ10 and green tea

Sources:

Park Y, Subar AF, Hollenbeck A, Schatzkin A. Dietary Fiber Intake and Mortality in the NIH-AARP Diet and Health Study. Arch Intern Med 2011.
Cassidy A, De V, I, Liu Y et al. Associations between diet, lifestyle factors, and telomere length in women. Am J Clin Nutr 2010;91:1273-80.

Post originally written to be posted here.

Living longer with an ideal BMI

Maintaining a healthy body mass index, or BMI, is one of the most important ways to help you live longer, according to a new study published in the December issue of New England Journal of Medicine.

BMI is not a perfect measure, but it is one of the simplest for estimating body weight. It is calculated by weight in pounds divided by height in inches squared and multiplying the number by 703, or by weight in kilograms divided by height in inches squared. What’s your BMI? Find out using this free calculator provided by the National Heart Lung and Blood Institute, of the National Institutes of Health.

The study’s findings support an optimal BMI in the “normal weight” range of 20 to 24.9, which is generally associated with the lowest risk of death from all causes including chronic diseases such as cardiovascular disease and cancer. The association was strongest among participants who were younger than 50 years old.

A BMI of 25 or more was associated with the highest mortality risks. The higher the BMI, the higher the likelihood of dying from cardiovascular disease.

“The results of our analysis are most relevant to whites living in affluent countries,” write the authors who pooled and analyzed data from 19 prospective studies encompassing 1.4 million white adults ages 19 to 80.

In the United States, among non-Hispanic whites, there was an estimated 11 percent of men and 17 percent of women with a BMI of 35 or higher in 2008.

The authors restricted the study to non-Hispanic whites based on self-reported ethnic group and controlled for pre-existing conditions, alcohol consumption, barbital status, education, and physical activity. They also excluded those with a BMI of less than 15 or higher than 50.

Smokers made up 25 percent of the study participants in the lowest BMI category of 15 to 18.4 and 8 percent of those in the highest BMI category.

Source: Berrington de Gonzalez A, Hartge P, Cerhan JR et al. Body-Mass Index and Mortality among 1.46 Million White Adults. NEJM 2010;363:2211-9.

Thoughts:

BMI is easy for anyone to measure, so this study gives us some back-up for using it as a way to speak to clients about real implications of obesity causing a shortened lifespan because of increased risk of cardiovascular disease and cancer.

It's important, however, to realize that while BMI may be easy it's possible for someone to be at a "normal weight" and still be "obese" -- dubbed normal weight obesity. This is still hazardous to your health, so you can't completely rely on BMI. Opt instead for body fat percentage measurement.

Aubrey de Grey Response to Rose and Coles

Aubrey de Grey

Next up at H+ @Caltech this afternoon was the famous and fast-talking Aubrey de Grey, who provided a response to previous talks by Michael Rose and Stephen Coles.

This is my take as how I understood the arguments. It was, admittedly, a bit hard to follow.

What we heard from Rose and Coles, explained de Grey, was that we have an exponential rise in deaths and then, we have what de Grey called, a "weird leveling off."

So, he said that as we get older, the data point to the fact that we eventually do reach a plateau in old age when mortality rates decline (passing the "aging phase" into a "biological immortality phase"), an argument of which Coles vehemently disagrees with.

He also said that it would probably not be a plateau like the type that Rose discussed in his talk, and as he showed in fruitflies.

Basically the data are sparse in these older populations, so there's no way we can really know what to expect.

"We definitely need more data," de Grey summarized.

And everyone else appeared to agree with that.

He also re-hashed his SENS approach for ridding the "accumulation of damage" that he says eventually causes the end of an individual's life.

De Grey pointed to the Gompertz Curve to support his arguments and the fact that because there are so few old people, there's too few data to make any kind of sense of whether there's an immortality phase or not.

Previously, about de Grey:
- Anti-Aging with Aubrey de Grey
- How to Prevent an Aging Crisis 

Building Methuselahs

Michael Rose, evolutionary biologist

Michael Rose is an evolutionary biologist, of University of California at Irvine, who knows how to sum up the complexity of aging.

He told us at H+ @ Caltech that aging is just a normal process of natural selection. It's obviously a "big picture" view versus a cellular or molecular view.

But to prove his point, he decided to trick natural selection and produce fruitflies that live five times longer than the average.

The trick? Take the fruitflies that can reproduce in old age, which still have most of their physiological function, and repeat.

Pretty simple. Eventually, you get longer-living fruitflies selected for late-life reproduction. And he shared data on how this all worked.

From the fruitfly data, Rose then explained, we can learn a bit about why humans age in the way they do, with pressures of reproduction playing in as a major factor. Also, we can make use of data on the flies and other animals that suggests that species enter a "biological immortality" phase once reaching an older age.

Then, he gave a two-part strategy into how humans can deter aging using "natural immortality technology." The strategy is easy and can be started tonight, he said.

What is natural for humans?
-It's not industrial lifestyle with cars, Twinkies, TV
-But is it the agricultural lifestyle or the hunter-gatherer lifestyle that is natural for us?

As an experimental evolutionist, Rose has research that shows that populations have adapted well to new environments in just 30 to 60 generations, so Eurasian populations are better adapted to the agricultural lifestyle.

How this happens? History in the environment, smaller effective population sizes, and lots of early accidental mortality leading to earlier plateaus.

So, people of ages under 30, should take an Andrew Weil approach to diet (as opposed to a Paleo diet and lifestyle) with plenty of fruits and vegetables, whole grains, and dairy.

However, he adds that as we age, the physiology of people with Eurasian ancestry progressively reverts back to the hunter-gatherer lifestyle.

"You will lose that adaptation to the novel environment as you age," Rose said.

So, the recipe for natural immortality?

- adopt a hunter-gatherer lifestyle after 40 if Eurasian, earlier if ancestry is less Eurasian

- use best modern medicine

- use autologous tissue repair when it becomes available (5+ years)

- use next-generation pharmaceuticals with less side effects

Interestingly, Aubrey de Grey expressed outrage that his recipe of immortality did not include rejuvenation research. He'll be speaking soon.

UPDATE: I ended up writing a more in-depth take into Michael Rose's talk for KurzweilAI, which can be found here.

Is there a maximum human lifespan?

Stephen Coles

"Death is an imposition on the human race and can no longer be tolerated" - Alan Harrington

With Harrington's quote, Stephen Coles opened his talk on whether or not there is a maximum limit to human lifespan at H+ @ Caltech in Los Angeles.

As a biogerontologist, Coles studies old people, as well as old yeast, microscopic worms, flies and primates. Each of these species have lifespan limits, and, indeed, he answers, there is a maximum number of years that humans live.

However, he adds, the more we understand aging, and the diseases that kill us, it is possible to extend life's max limit.

"All bets are off if we can do something about it," Coles said.

Although, he explains that the entire process of aging is so complex that it is sort of like the blind men touching the elephant because, if your blind, it has a different shape depending on where you're touching.

Putting together the pieces that make up aging is the AMMG, which has met several times in the last couple of decades and has an accumulated "a whole lot of data."

Coles remains optimistic that Calment Limit of 120 will be surpassed, as he shows us data on the increase in the number of centenarians and supercentenarians in the world.

In addition, the average life expectancy has increased over these years. 

Average life expectancies historically:

100 KYA 18

5 KYA (Ancient Egypt) 25

1400 AD (middle ages) 30

... Anyone else know the rest?

Most of us now die in our 70s from cardiovascular disease and cancer.

There's seriously a revolution going on in the understanding of aging, partly because of Stephen Coles's research in supercentenarians, including analysis of there genomes, etc. He's also worked with autopsies of centenarians.

Coles also showed data on autopsies of supercentenarians that revealed that most of them succumb to TTR (transthyretin amyloidosis).

He argues that if real life extension is to come in the future because of new technologies, then "we need a bridge plan."

These bridges are outlined here . 

What can beetles tell us about slowing aging? Answers are in the mitochondria

Mitochondrial genes influence life expectancy in beetles, a new study reports.

Genetic research into aging and longevity revolves mainly around the nuclear genome, which encodes most of our multicellular bodies, but a new Monash University study performed on beetles suggests shifting focus to the mitochondrial genome.  

The mitochondria—kidney-shaped organelles often referred to as the cell's powerhouses—each contain their own set of DNA, passed on from mother to offspring, and according to the study, it's these strands that may hold key genes that determine one's life expectancy, at least in bugs.  

The study, published in the August issue of The American Naturalist, found evidence that particular combinations of genes (haplotypes) in the mitochondrial genome influenced lifespan in a species of seed beetles (Callosobruchus maculates).  

As a result, the research supports growing evidence that particular mitochondrial gene combinations could also play a major role in accelerating the aging process in humans because they could cause mitochondria to produce greater amounts of toxic molecules called free radicals causing oxidative damage to cells, cellular proteins and DNA.  

Evolutionary biologist Damian Dowling of Melbourne, who conducted the study, hopes his research will help medical scientists identify which gene combinations accelerate aging, as well as develop gene therapies that alter the combinations, or develop antioxidant therapies that neutralize free radicals and protect cells from oxidative damage. Do mothers show favoritism toward daughters?  

Although Dowling found his discovery interesting, he said it was not the original intent of his research; in fact, he was testing a debated theory that mitochondrial genes make an impact on the tug-of-war between the sexes in the beetles. Previous research in beetles and fruit flies has explored a ubiquitous phenomenon in insects commonly called the "cost of mating"—that is, that the simple act of sexual reproduction can take a toll on mothers, and sometimes fathers, by reducing their life expectancy.  

Dowling’s wanted to find out if mitochondria bestowed any reward to female beetles. He explained to me: "Because the mitochondrial genome is maternally inherited it has been hypothesized that it will take the female's best interests at heart." 

But, he adds, "Our study was the first experimental test of this idea, and we didn't support the controversial idea." However, what Dowling did find was something more exciting—that different mitochondrial gene combinations, sourced from different geographic locations from around the globe, produced large differences in life spans in the beetles.  

“Beetles that harbored certain mitochondrial DNA sequences could live up to 30 percent longer,” he told me. Thirty percent longer is about 20 more days for the life of a beetle, which is nothing short of a leap for the crawling critters—when scaled up to human years, it amounts to adding about 23 more years.