An Apple a Day – Or Perhaps Several

By Bret Kulakovich

It is certainly something that is on our minds. The seasons have turned through another rotation of holidays, and we find ourselves contemplating our recent enthusiasm at the dinner table.

Caloric restriction, as you may know, is the limitation of food intake to produce positive health and longevity results. In a way, while it would seem similar, it is the opposite of malnutrition, since the focus of caloric restriction is the regulation of the proportions of certain foods, while maintaining proper intake of vitamins and micronutrients. The average person is recommended a daily intake of 2000 to 2500 calories, while caloric restriction would prefer to put you in the 1800 calorie range, depending on your basal metabolic rate, or BMR.

While I do not consider myself “restricted” I am careful of what I eat. I try to measure calories, keep track of my sugars, and drink from vessels with ounces clearly marked on the side to remain mindful of how much I drink, and of what. I have over the years given up on soda except as a dessert option, and have been mindful of keeping up my water consumption since I read the science fiction novel Dune in the early 80s. I find using such a graduated drinking vessel helpful especially in the Fall when hydration can become more challenging in the Northeast. Humidity can drop like a stone in late October and can go down by 25% or more in a single week.

Earlier studies in caloric restriction, or “CR”,  led to theories that oxidative stress, caused by food intake, may be a cause of aging. The ingestion and processing of food is a constant source of free radicals and peroxides, many of which cause damage to just about every cellular component. This interaction in turn creates a wide variety of oxidants, some of which can go on to combine with LDL in your bloodstream to form plaque, or join with one another to produce even more adverse biochemical changes.. Some chemicals, such as organic hydroperoxide and hypochlorous acid (ROOH and HOCl, respectively) are then free to cause additional damage to cell structures and lipids, and break down beneficial proteins.

The accumulation of this damage is seen as a potential source or trigger of a great variety of diseases, including heart disease, Parkinson’s disease, and Alzheimer’s disease. The trend to treat free radicals with antioxidants in the past decade can find its roots firmly in this earlier research.

New findings are beginning to support the contention that age related hearing loss could be the result of a protein (known as Bak) that is leaked from mitochondria that have been damaged by these stresses. This protein goes on to damage the cells in the cochlea. We should consider the sensitivity of the cochlea and what damage may be occurring in other parts of the body that does not have such an apparent effect. This could be evidence that more robust systems are also losing function due to our diets.

Of course, human trials of caloric restriction – or trials of any organism with a significant lifespan – will take some time to complete. A few of the larger studies, such as CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) are underway to study the effect of CR on healthy human subjects. The study is looking not only for positive change in lifespan, but also for the mitigation of other age-related problems such as cancer and cardiovascular disease.

To date, the findings surrounding CR support many benefits, including decreased insulin resistance, positive weight loss, and lowered cholesterol – all the things you would normally associate with what would be termed “proper diet and exercise.” Subjects also displayed lower blood pressure, reduced fasting glucose, and higher HDL cholesterol levels.

What is unusual is that the findings show a lower standing body temperature, which in itself has been considered a key to longevity. Analysis has also shown decreased levels of radicals such as nitric oxide and superoxide in the blood, as well as other benefits that are not usually attributed to the traditional proper diet and exercise regimen.

Recently there have been publications with some pretty strong findings. The research indicates that just about any complex organism has the same physiological response to caloric restriction, and that CR plays a consistent and significant role in “life span regulation.” Some very promising results have come out of a study at Harvard that showed reversal of age-based nerve damage to the neuromuscular system.

The neuromuscular system is the pathway that the signals from the brain travel in order to reach your muscle fibers. It is similar in layout to a tree, with the branches ending in neuromuscular synapses, where the nerves plug in to receivers in the muscle tissue itself. Like a tree, over time these connections can weaken, bend, or even begin to wither. This degeneration causes electrical interference to signals coming from the brain that can eventually cut off communication to muscle fibers entirely, resulting in a type of muscular atrophy known as Sarcopenia. This is one of the key components of frailty due to the aging process.

The Harvard findings show that while exercise seemed to reverse a good amount of the synaptic damage in mice, caloric restriction reversed all of the damage. Work remains to be done to see that the structural preservation of neuromuscular synapses is relative to their proper function.

Another recent study from the University of Wisconsin–Madison has shown that an enzyme, known as Sirt3, is produced in greater amounts in calorically restricted mice. Sirt3 is thought to play a role in the “reprogramming” of the mitochondria inside the cell, due to the change in metabolism of restricted individuals. Experiments also showed that Sirt3 protected cells from oxidative stress and death caused by free radicals. While past studies have shown a relationship between the family of enzymes known as “Sirtuins” – of which Sirt3 is one – this is the first to conclusively show the role that a sirtuin plays in cellular preservation. So direct are the findings of this study, that one questions how soon a product could come to market. A compound to deliver Sirt3 where needed, or perhaps ldh2, the enzyme it induces, would I think be a high priority for a pharmaceutical company.

In this age we take everything into our own hands, and handle the advice of experts in application to ourselves. We want to know the diagnosis, we want to take copies of our MRIs home and look at them with iRad or OsiriX, to rotate the soft tissue display and see the point of pressure on the nerve. For those who want to have a go at self-maintenance and self-regulation there is of course the CRON diet and its variants, which focus on getting yourself to a “set-point” in your weight and adhering to certain volumes of particular foods, while eschewing others. There are a variety of online calculators and mobile applications to assist with calculating your BMR (Basal Metabolic Rate) should you wish to do so. Starting numbers for your Body Mass Index and other important information is just a doctor’s visit away, although a variety of BMI calculation tools are readily available, including electronic bathroom scales that now have built-in sensors for BMI, bone mass, hydration, and other important variables.

With regard to aging, it appears that what we are looking at are two distinct strategies: on the one, the evasion of damage, the other, the reversal of damage. Nothing stops you from engaging either stratagem, however some become more important during different life cycles – engaging in a caloric restriction regimen late in life may be ineffective in certain systems.

It is difficult to ignore such compelling evidence. Having only gotten any distance from soda in the past few years, larger changes to diet – and the infrastructure to support such a change – can seem daunting. The largest complaints from participants in the studies have not been about hunger pains, foregoing cake, or appetite fatigue. They have spoken most of all about needing to track meals, eat very specifically, and write everything down. I may be able to ease into something like this, especially if I continue to follow this work. For now I think I will head outside, feed our chickens, and try to walk off a few “unrestricted” calories.

Bret Kulakovich lives in Lakeville, MA with his wife Sarah and their three children. They have been Alcor members since 2005. Bret and his family were also featured in a member profile in Cryonics magazine, Summer 2006, Volume 27:3

References

Someya, S., Yu, W., Hallows, W., Xu, J., Vann, J., Leeuwenburgh, C.,  Tanokura, M., Denu, J.,  & Prolla, T. A. (2010, November 24). Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction. Cell, 143, 802-812.

Valdez, G., Tapia, J., Kang, H., Clemenson Jr., G. D., Gage, F. H.,  Lichtman, J. W., & Sanes, J. R. (2010, August 17). Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise. Proceedings of the National Academy of Sciences, 107, 14515-14938.

Chou, S.H., Lee, Y. C., Huang, C. F., Wang, Y.R., Yu, H.P., & Lau Y.T. (2010, March 25). Gender-specific effects of caloric restriction on the balance of vascular nitric oxide and superoxide radical. Cardiovascular Research, 87, 751-759.

Someya, S.,  Xu, J., Kondo, K., Ding, D.,  Salvi, R. J., Yamasoba, T., Rabinovitch, P. S., Weindruch, R.,  Leeuwenburgh, C., Tanokura, M., & Prolla, T. A. (2009, November 17). Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proceedings of the National Academy of Sciences, 106, 19432-19437.

Vaquero, A., Reinberg, D. (2009, July 16). Calorie restriction and the exercise of chromatin.