Slow aging? – Sun 9.10.17
I like Lon Kilgore. He has an extensive training and education background. Here is his newest article at the CrossFit Journal:
Aging and exercise: Do this and you’ll slow aging. Eat this, or less of it, and you’ll live longer.
Before “do this” and “do that,” many of us simply need to know what aging is.
Most people associate aging with the passing of years—the inevitable journey through youth, adulthood, older age and a period of decrepitude followed by death. Despite a general understanding that age wears the body down and slows its functions, they don’t think of the anatomical and physiological realities of accumulated usage on the body and its systems.
Let’s be blunt: Nothing stops aging. People have been trying to find the mythical and pharmacological fountain of youth for millennia, and all have failed because you can’t stop the clock.
You can, however, change the outcomes of aging if you understand the concept with respect to human biology.
You can find myriad definitions of aging in print, some founded in science, some founded in myth or common beliefs, and most related to some very specific set of biochemical systems, tissues or appearances.
Some definitions are couched in a specific academic discipline. For example, in psychology you might find aging defined as follows: Age is the level of mental, emotional or educational development of a person as determined by a testing comparison of that person’s score with average test scores for other persons of the same chronological age.
Within the fitness industry, we are generally more closely guided by anatomical and physiological principles and outcomes. In this domain, the most common concept of aging is something like this: Aging is the deterioration of physiological function and anatomical structure over time, which creates intrinsic conditions of low organismic viability and high vulnerability.
But this definition is only part of the picture. In 1929, Albert Warthin published “Old Age” (1), in which he wrote:
“The senescent process is potent from the very beginning, involution is a biologic entity equally important with evolution—its processes are as physiologic as are those of growth. It is, therefore, inherent in the cell itself, an intrinsic inherited quality of the germ plasm, and no slur or stigma of pathology should be cast upon this process. Senescence is due primarily to the gradual weakening energy charge set in action by the moment of fertilization.”
Aging isn’t simply the decline of life but the complete life cycle. Further, Warthin proposed a timeline of aging. From birth to the mid-to-late 20s, human life is a period of evolution, a period in which the aging process is marked with many large developmental changes (not evolution as in Darwinian theory). Considering the magnitude of anatomical and physiological changes that occur between birth and the mid-20s, it is the young who age the fastest.
From the end of the period of evolution up to the late 50s or early 60s, humans are in a period of maturity in which changes to structure and function are a net of zero—essentially a balance between environmental demand and adaptive ability. As the period of maturity ends, the period of involution begins, and the body enters senescence and declines until death. It is notable that Warthin suggested the normal cycle of human life would end—death by age not by pathology—at approximately 90.
What we do in the stage of maturity and involution can directly affect the latter stages of aging.
Anatomy of an Aging Chromosome
Most aged people will tell you things break down more easily when they are older. This is indicative of the degradation of molecules, cells and tissues over time. Changes occur from the imperceptible molecular level up to observable levels that involve whole tissues and systems.
At the molecular level are telomeres, tiny bits of DNA that act as caps at the ends of chromosomes that change with age. For each year of chronological age, the size of the telomere cap gets smaller. Research suggests we lose about 24-27 base pairs from the DNA composing the telomere with every year of age after maturity (2). The aglets on your shoestrings provide a crude parallel for the function of telomeres: Aglets prevent fraying of the ends of the strings over time. Similarly, telomeres protect chromosomes from biochemical erosion over time. If they were not present, we would lose genetic information and functional genes with every cell division.
One of the important and compelling concepts surrounding telomere length is that the erosion of the telomere serves as a biological countdown clock. When the telomere of one or all of the 92 telomeres in a human cell is shortened to a certain length, cell senescence occurs. Senescence is, in part, the inability of a cell to duplicate itself. If cells cannot perform their replicative duties, they cannot replace themselves and repair tissues.
Think about this: Shortened or absent telomeres appear to impair repair and regeneration of cells and tissues. What happens to our ability to recover from training as we age? Most masters athletes will tell you they can’t recover as quickly as they did when they were in their teens and 20s. This suggests adaptive capacity, or physiological function, is slowed by the biochemical and anatomical changes related to telomere length. But does any evidence support this leap in concept?
While causality in humans has not been demonstrated, it has been shown through the use of “knock-out mice” from which a specific gene or genes were removed. Humans have been subject to extensive research on the length of telomeres in a number of pathological conditions. Telomere length is associated with a number of age-related syndromes and diseases:
- High blood pressure (3).
- Myocardial infarction—heart attack prior to 65 (4).
- Diabetes —Type 1 and 2 (5,6).
- Alzheimer’s disease (7).
- Cancer (8).
- Impaired glucose tolerance (9).
Believe it or not, graying hair and hair loss (10), as well as apparent skin age (11), might be associated with telomere length and the telomere’s ability to stabilize DNA.
So it appears that erosion of telomeres might affect many aspects of appearance and function as we age. But the astute among you will be quite right to point out that association (correlation) does not establish causation. We are, however, talking about the biological dogma first introduced by Francis Crick (of Watson and Crick fame): DNA codes for RNA, which codes for protein. If the structure of DNA is altered, as occurs with telomere shortening, then everything downstream can be affected.
(Most studies on whether exercise or physical activity delay telomere erosion are based on subject recall and correlation. We do have to be cautious in our interpretations of data relative to telomeres and longevity. Further, nearly all telomere studies use white blood-cell [leukocyte] telomeres as their measurement, intended to represent whole-organism telomere length. So when we read that muscular exercise affects telomere length, it is not referent to the DNA in muscle; it is referring to effects on blood-cell DNA. It is a proxy measure, not a direct measure.)
Of specific relevance to fitness are the effects of aging on our muscles. As expected, and as reported by older trainees, age brings about a decline in the regenerative capacity of muscle cells and tissue. We can see evidence of this in impairment of regeneration of cells and tissues after injury, where older individuals have more protracted and incomplete recoveries after injury (12).
Regeneration of muscle cells is thought to result from the functional compromise of satellite cells, the resident stem cells of muscle. As we age, our satellite cells experience a decrease in proliferative capacity and ability to differentiate, and they appear to decrease in number (13). This is partially explicative of why recovery from training is slower as we age.
Adding satellite cells from young mice “rejuvenated” satellite-cell function in older mice (14), but we can’t just add new satellite cells to our muscles willy-nilly even if we could find a source. We can, however, do things that keep them present for longer.
Satellite cells are a source of new DNA for active muscle cells. These stem cells are recruited to proliferate and differentiate into nascent muscle cells by training. This injection of new DNA and cells into working muscles might provide a source of longer telomeres, but this is conjecture as skeletal muscle cells are multinucleated and determining the behavior of newly incorporated nuclei is currently not possible because the new nuclei are drowned within the many thousands of existing nuclei. But we can estimate that the nuclei of a muscle turn over at about 2 percent per week (15), and we also know that muscle-associated satellite cells maintain their telomerase (telomere-maintaining enzyme) activity even in old muscle (16).
Changing Outcomes With Exercise
But let’s go back to the idea that we can alter the latter stages of aging. Can we preserve anatomical structure and physiological function by doing certain things or doing certain things better?
In a recent survey-based study it was noted that women who were physically active to the level of jogging 30 minutes per day five days per week on a multi-year basis had significantly longer telomeres than sedentary individuals. The study indicated that 40 minutes of activity was required to produce the same benefit for men. The authors calculated a loss of 15.6 base pairs per year, and the difference between sedentary and exercising populations represented an additional 8.8 years of lifespan (2). While the study relied on self-reported data combined with blood analysis and did not discriminate, exercise can slow the erosion of telomeres.
But let’s be even more specific: What about high-intensity exercise? How about the idea that the stronger you are, the longer your telomeres are likely to be? For example, highly trained subjects (they could squat 292.5 kg/644 lb. on average) had telomere lengths greater than those in subjects who exercised once per week or less (17). So at least some data suggests a relationship between intensity and telomere length, but the subjects in this study were very strong and dose response between strength and telomere length is unknown.
Endurance is similarly associated with longer telomeres. Older individuals who have higher aerobic capacity (VO2 max) and who train five or more days per week have longer telomeres than their peers who train less than two days per week or have a lower VO2 max. Further—and very important here—older individuals who have high aerobic capacity have telomere lengths similar to those of young trained adults (18). If exercising and enhanced fitness produce “anti-aging” results, then we would expect that not exercising would do the opposite. The data seems to confirm this conjecture, and we also have data that suggests no training might produce adverse effects when we consider obesity. High body-mass indexes at ages less than 60 are correlated with shorter telomere lengths (19). Yes, BMI is a measure rife with shortcomings, but clinicians like to use it because it’s easy to do so, and the data can give us a hint of a relationship.
It should be evident that frequent and long-term training—lifting, running and more—seems to protect telomere length. Conversely, sitting on your butt and packing on pounds of body weight appears to be a recipe for accentuated telomere erosion and a shorter lifespan.
Muting the Benefit
Sadly, many things we do and consider innocuous might negate or reduce the positive effects of exercise.
For example, caffeine reduces telomere length by 35 base pairs for each 100 mg consumed on a regular basis (20). This, however, is not catastrophic news. Interestingly, coffee, one of the primary sources of caffeine, has a synergistic effect on telomere length. For each 3.5 oz of coffee consumed on a regular basis, telomere length increases by 18 base pairs in women and 12 base pairs in men. So it seems that caffeine source is an important consideration: Coffee seems to be good while other caffeinated beverages seem to be bad with respect to telomere length.
Most humans tend to be sun worshipers, basking in the rays as soon as weather permits. Although we associate sun exposure with vitamin D synthesis and many other health benefits, direct sun exposure shortens skin telomere lengths more than if sunscreen is used to prevent UV penetration (21).
In our day-to-day lives we experience stress in a variety of forms and environments. Although we often consider this par for the course, stress can have a profound effect on us: Psychological stress has been associated with decreased telomere length (22). So if we do nothing about the stress we perceive in our lives, we might be paving the road to faster physiological dysfunction. What can we do about it? Quit our jobs? Become hermits? We don’t have to go that far. We have only to go as far as the gym because exercise reduces perceived life stress (23). If you are fit or getting fitter, you cope with external stress better. The stress doesn’t go away; you simply cope with it better, and thus the stress becomes less of a factor.
We can directly create the conditions associated with longer telomeres and a more elegant passage of years by training to improve strength and endurance. We can also support those conditions with relatively straightforward changes in lifestyle, such as eating better, watching our weight and working to mitigate the effects of stress from all sources.
For many of us or for our trainees, however, these simple changes are seen as intrusive or costly alterations to work-life balance. But this is not the case. CrossFit is time efficient and can develop strength and endurance in relatively short training sessions. CrossFit can also circumvent another issue—cost, a perennial barrier—because CrossFit publishes workouts and a host of training resources that are free to all on CrossFit.com.
As much as we would like to be able to turn back time, or to be able to slow its progression, available data strongly suggests that we cannot. What we can do is take steps, preferably steps to the gym, to ensure the inevitable march of time and decline to death occurs as late in life as possible.
- Warthin, AS. Old age. New York: Paul B. Hoeber Inc., 1929.
- Tucker L. Physical activity and telomere length in U.S. men and women: An NHANES investigation. Preventive Medicine 100: 145-151, 2017.
- Bhupatiraju C et al. Association of shorter telomere length with essential hypertension in Indian population. American Journal of Human Biology 24(4): 573-8, 2012.
- Brouilette S et al. White cell telomere length and risk of premature myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology 23(5): 842-6, 2003.
- Uziel O, Singer JA, Danicek V. Telomere dynamics in arteries and mononuclear cells of diabetic patients: Effect of diabetes and of glycemic control. Experimental Gerontology 42: 971-8, 2007.
- Salpea KD, Talmud PJ, Cooper JA. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis 209(1): 42-50, 2010.
- Panossian LA et al. Telomere shortening in T cells correlates with Alzheimer’s disease status. Neurobiology of Aging 24(1): 77-84, 2003.
- Willeit P et al. Telomere length and risk of incident cancer and cancer mortality. Journal of the American Medical Association 304(1): 69-75, 2010.
- Klelia DS, Humphries SE. Telomere length in atherosclerosis and diabetes. Atherosclerosis 209: 35-38, 2009.
- Nishimura EK, Granter SR, Fisher DE. Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche. Science 307(5710): 720-4, 2005.
- Magner U et al. Topical equol preparation improves structural and molecular skin parameters. International Journal of Cosmetic Science: Jun 2, 2017.
- Di Iorio A et al. Sarcopenia: Age-related skeletal muscle changes from determinants to physical disability. International Journal of Immunopathology and Pharmacology 19: 703-719, 2006.
- Gopinath SD, Rando TA. Aging of the skeletal muscle stem cell niche. Aging Cell 7: 590-598, 2008.
- Conboy IM et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433: 760-764, 2005.
- Schmalbruch H, Lewis DM. Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles. Muscle and Nerve 23(4): 617-26, 2000.
- O’Connor MS, Carlson ME, Conboy IM. Differentiation rather than aging of muscle stem cells abolishes their telomerase activity. Biotechnology Progress 25(4): 1130-7, 2009.
- Kadi F et al. The effects of regular strength training on telomere length in human skeletal muscle. Medicine and Science in Sports and Exercise 40(1): 82-7, 2008.
- LaRocca TJ, Seals DR, Pierce GL. Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity. Mechanisms of Ageing and Development 131: 165-7, 2010.
- Müezzinler A et al. Body mass index and leukocyte telomere length dynamics among older adults: Results from the ESTHER cohort. Experimental Gerontology 74: 1-8, 2016.
- Tucker L. Caffeine consumption and telomere length in men and women of the National Health and Nutrition Examination Survey (NHANES). Nutrition & Metabolism 14: 10, 2017.
- Ikeda H et al. Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis. Human Pathology 45(3): 473-480, 2014.
- Epel ES et al. Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences 101(49): 17312-5. 2004.
- Gerber M et al. Increased objectively assessed vigorous-intensity exercise is associated with reduced stress, increased mental health and good objective and subjective sleep in young adults. Physiology and Behavior 135: 17-24, 2014.