More exercise correlates with younger body cells.

Reynolds points to work by Loprinzi et al. showing physicaly active people have longer telomeres at the end of their chromosomes' DNA strands than sedentary people. (A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration from from fusion with neighboring chromosomes. It's length is a measure of a cell's biological age because it naturally shortens and frays with age.) Here is their abstract, complete with three (unnecessary) abbreviations, LTL (leukocyte telomere length), PA (physical activity) and MBB (movement based behaviors), that you will have to keep in your short term memory for a few seconds: 

INTRODUCTION: Short leukocyte telomere length (LTL) has become a hallmark characteristic of aging. Some, but not all, evidence suggests that physical activity (PA) may play an important role in attenuating age-related diseases and may provide a protective effect for telomeres. The purpose of this study was to examine the association between PA and LTL in a national sample of US adults from the National Health and Nutrition Examination Survey.  

METHODS: National Health and Nutrition Examination Survey data from 1999 to 2002 (n = 6503; 20-84 yr) were used. Four self-report questions related to movement-based behaviors (MBB) were assessed. The four MBB included whether individuals participated in moderate-intensity PA, vigorous-intensity PA, walking/cycling for transportation, and muscle-strengthening activities. An MBB index variable was created by summing the number of MBB an individual engaged in (range, 0-4).  

RESULTS: A clear dose-response relation was observed between MBB and LTL; across the LTL tertiles, respectively, the mean numbers of MBB were 1.18, 1.44, and 1.54 (Ptrend less than 0.001). After adjustments (including age) and compared with those engaging in 0 MBB, those engaging in 1, 2, 3, and 4 MBB, respectively, had a 3% (P = 0.84), 24% (P = 0.02), 29% (P = 0.04), and 52% (P = 0.004) reduced odds of being in the lowest (vs highest) tertile of LTL; MBB was not associated with being in the middle (vs highest) tertile of LTL.  

CONCLUSIONS: Greater engagement in MBB was associated with reduced odds of being in the lowest LTL tertile.

More exercise correlates with younger body cells.

Reynolds points to work by Loprinzi et al. showing physically active people have longer telomeres at the end of their chromosomes' DNA strands than sedentary people. (A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. It's length is a measure of a cell's biological age because it naturally shortens and frays with age.) Here is their abstract, complete with three (unnecessary) abbreviations, LTL (leukocyte telomere length), PA (physical activity) and MBB (Movement based behaviors), that you will have to keep in your short term memory for a few seconds:

INTRODUCTION: Short leukocyte telomere length (LTL) has become a hallmark characteristic of aging. Some, but not all, evidence suggests that physical activity (PA) may play an important role in attenuating age-related diseases and may provide a protective effect for telomeres. The purpose of this study was to examine the association between PA and LTL in a national sample of US adults from the National Health and Nutrition Examination Survey.

METHODS: National Health and Nutrition Examination Survey data from 1999 to 2002 (n = 6503; 20-84 yr) were used. Four self-report questions related to movement-based behaviors (MBB) were assessed. The four MBB included whether individuals participated in moderate-intensity PA, vigorous-intensity PA, walking/cycling for transportation, and muscle-strengthening activities. An MBB index variable was created by summing the number of MBB an individual engaged in (range, 0-4).

RESULTS: A clear dose-response relation was observed between MBB and LTL; across the LTL tertiles, respectively, the mean numbers of MBB were 1.18, 1.44, and 1.54 (Ptrend less than 0.001). After adjustments (including age) and compared with those engaging in 0 MBB, those engaging in 1, 2, 3, and 4 MBB, respectively, had a 3% (P = 0.84), 24% (P = 0.02), 29% (P = 0.04), and 52% (P = 0.004) reduced odds of being in the lowest (vs highest) tertile of LTL; MBB was not associated with being in the middle (vs highest) tertile of LTL.

CONCLUSIONS: Greater engagement in MBB was associated with reduced odds of being in the lowest LTL tertile.

Does exercise change your brain?

After yesterday's post suggesting no effects of common dietary supplements on cognitive changes with aging, I thought I would note work regarding exercise and brain health. mentioned by Reynolds, in particular a study by Burzynska et al. that monitored the daily activities of non-athletes:

...the most physically active elderly volunteers, according to their activity tracker data, had better oxygenation and healthier patterns of brain activity than the more sedentary volunteers — especially in parts of the brain, including the hippocampus, that are known to be involved in improved memory and cognition, and in connecting different brain areas to one another. Earlier brain scan experiments by Dr. Burzynska and her colleagues had established that similar brain activity in elderly people is associated with higher scores on cognitive tests.

Again, there is the caveat that a correlation does not prove a cause.

Exercise for the aging brain - how much is necessary?

Gretchen Reynolds points to interesting work on exercise and the aging brain by Vidoni et. al. Increasing amounts of aerobic exercise (75, 150, 225 minutes per week of walking) correlated with correspondingly increased cardiorespiratory fitness, but the degree of improvement in thinking skills, compared with non-exercising controls, was the same regardless of the duration of exercise. This suggests that a small dose of exercise may be sufficient to improve many aspects of thinking.

Habitual exercise correlates with lower distractibility.

Yet another demonstration of the salutary effects of long term exercise on mental function:

Aging is associated with compromised executive control functions. Several lines of evidence point to beneficial effects of physical activity on cognition which indicate that regular physical activity may counteract the age-related decline of some executive functions. Here, we investigate the effects of lifelong physical activity (about 50 years) on interference processing in two matched groups of 20 physically high active and 20 low active healthy older men using event-related potentials (ERPs). In a low interference block of the Stroop task, participants had to indicate the meaning of color-words, while color was either compatible or incompatible with the meaning. In the high interference block, participants were asked to respond according to the ink color of the word and to ignore its meaning. Physically active seniors showed faster reaction times, lower individual variability in reaction times, and higher accuracy compared to low active seniors, particularly in the high interference block. This result was confirmed in the classic paper-and-pencil version of the Stroop task showing higher interference score in the low active than high active individuals. ERPs revealed a shorter latency of the P2 and generally more negative amplitudes of the fronto-central N2 and N450 components in the high active group compared to the low active group. The amount of interference was negatively correlated with objectively measured fitness and self-reported physical activity. The positive effect of physical fitness on interference processing in the behavioral data was related to N2 and N450 amplitudes. Taken together, this suggests that seniors reporting long-term physical activity may exhibit generally enhanced activity in the frontal cortex which enables more efficient interference resolution in the Stroop task.

New stuff on exercise, brain, and body.

I'll use this post to point readers to several recent interesting articles on physical activity. Hutchinson does a review of work that distinguishes the effect of strength and endurance training versus balance and stability training. The former isn't all that useful without the later, especially in older adults (have you tried standing on one leg with your eyes closed lately?). A German study followed aged adults for 12 months comparing those who did cardiovascular (walking) exercise three times a week, with those who did coordination training. Both groups showed improvement in cognitive functioning, but in different ways. Cardiovascular training was associated with an increased activation of the sensorimotor network, whereas coordination training was associated with increased activation in the visual–spatial network. Mouse studies show that aerobic exercise and strength training trigger brain chemicals that enhance neuron growth and survival, while balance and coordination exercises also recruit higher-level cognitive processes that seem to increase the number of synapses connecting neurons. Work by Kumpulainen et. al. suggests that novelty and unpredictability (as in gymnasts or dancers), rather than repetition (as in endurance athletes), are essential in brain plasticity and engagement.

In another item, Reynolds updates the story on the beneficial effects of intense interval training. Just a few minutes of very intense exercise are much more effective in improving health and cardiovascular fitness than slow and steady repetitive exercise. To try to deal with the problem that most people really don't enjoy zonking themselves out with intense intervals, Bangsbo and collaborators tried a different approach, asking runners to run gently for 30 seconds, then accelerate to a moderate pace for 20 seconds, then sprint as hard as possible for 10 seconds. Repeat five times, rest for a bit, and continue the sequence during a 5-km run. They observed the same beneficial effects on blood pressure and endurance observed with more arduous (several minute) bouts of high intensity training. I tried this 30-20-10 sequence with my favored aerobic exercise, swimming (just counting the intervals to myself made them pass more quickly), and I came out of the routine feeling way more wired than after my usual moderately active swim period.

Lack of exercise disrupts body’s rhythms.

Natural daily rhythms in spontaneous movement patterns in both humans and mice show scale invariance, i.e., movement patterns repeat over time scales of minutes to hours. These scale invariant patterns decay with aging in both humans and mice, apparently correlating with progressive dysfunction of circadian pacemaker circuits in the brain's suprachiasmatic nucleus. Scheer and collaborators have now shown that in both aged and young mice exercise is a crucial variable. Loss of scale invariance associated with both inactivity and aging can be restored by exercise, even in old animals.

In healthy humans and other animals, behavioral activity exhibits scale invariance over multiple timescales from minutes to 24 h, whereas in aging or diseased conditions, scale invariance is usually reduced significantly. Accordingly, scale invariance can be a potential marker for health. Given compelling indications that exercise is beneficial for mental and physical health, we tested to what extent a lack of exercise affects scale invariance in young and aged animals. We studied six or more mice in each of four age groups (0.5, 1, 1.5, and 2 y) and observed an age-related deterioration of scale invariance in activity fluctuations. We found that limiting the amount of exercise, by removing the running wheels, leads to loss of scale-invariant properties in all age groups. Remarkably, in both young and old animals a lack of exercise reduced the scale invariance in activity fluctuations to the same level. We next showed that scale invariance can be restored by returning the running wheels. Exercise during the active period also improved scale invariance during the resting period, suggesting that activity during the active phase may also be beneficial for the resting phase. Finally, our data showed that exercise had a stronger influence on scale invariance than the effect of age. The data suggest that exercise is beneficial as revealed by scale-invariant parameters and that, even in young animals, a lack of exercise leads to strong deterioration in these parameters.

Physical activity's 'modest' effects on cognitive vitality

Prakash et al., in the Annual Review of Psychology, have reviewed the epidemiological literature on physical activity and exercise and their relationship to cognition and age-associated neurodegenerative diseases such as Alzheimer's disease. While the abstract uses the word "modest" to describe the effect of physical activity on preserving or enhancing cognitive vitality, the numerous studies and meta-analyses they cite demonstrate a reduction in all-cause mortality of 20-30% associated with physical activity, and a 38% reduction in risk of cognitive decline in nondemented participants with high physical activity levels, and a 35% reduction in participants with low to moderate levels. Thus there is no evidence for an increase in relative risk reduction in cognitive decline as a function of increasing levels of physical activity. Here is their abstract:

We examine evidence supporting the associations among physical activity (PA), cognitive vitality, neural functioning, and the moderation of these associations by genetic factors. Prospective epidemiological studies provide evidence for PA to be associated with a modest reduction in relative risk of cognitive decline. An evaluation of the PA-cognition link across the life span provides modest support for the effect of PA on preserving and even enhancing cognitive vitality and the associated neural circuitry in older adults, with the majority of benefits seen for tasks that are supported by the prefrontal cortex and the hippocampus. The literature on children and young adults, however, is in need of well-powered randomized controlled trials. Future directions include a more sophisticated understanding of the dose-response relationship, the integration of genetic and epigenetic approaches, inclusion of multimodal imaging of brain-behavior changes, and finally the design of multimodal interventions that may yield broader improvements in cognitive function.

Another study on exercise keeping us young - and other fitness trends

Because there are currently no generally agreed on markers of human ageing, Pollock et al. (see review by Reynolds) decided to examine the relationship between age and physiological function by removing inactivity as a factor. They recruited and performed physiological and psychological profiling on a cohort of 55-79 year old very active cyclists. As a group, even the oldest cyclists had younger people’s levels of balance, reflexes, metabolic health and memory ability. Despite studying a large number and diverse range of indices, the authors were not able to identify a physiological marker that could be used to reliably predict the age of a given individual.

Other items from my queue of potential posts:

Reynolds does a review of recent fitness trends such as the super short workout with high intensity bursts, and Brody adds further information on high intensity interval training as an antidote to several chronic ilnesses.

Exercise and intermittent fasting improve brain plasticity and health

I thought it might be useful to point to this brief review by Praag et al. that references several recent pieces of work presented at a recent Soc. for Neuroscience Meeting symposium. The experiments indicate that exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases by enhancing neurogenesis, synaptic plasticity and neuronal stress robustness.  (Motivated readers can obtain the article from me.) Here is their central summary figure:

Exercise and IER/fasting exert complex integrated adaptive responses in the brain and peripheral tissues involved in energy metabolism. As described in the text, both exercise and IER enhance neuroplasticity and resistance of the brain to injury and disease. Some of the effects of exercise and IER on peripheral organs are mediated by the brain, including increased parasympathetic regulation of heart rate and increased insulin sensitivity of liver and muscle cells. In turn, peripheral tissues may respond to exercise and IER by producing factors that bolster neuronal bioenergetics and brain function. Examples include the following: mobilization of fatty acids in adipose cells and production of ketone bodies in the liver; production of muscle-derived neuroactive factors, such as irisin; and production of as yet unidentified neuroprotective “preconditioning factors.” Suppression of local inflammation in tissues throughout the body and the nervous system likely contributes to prevention and reversal of many different chronic disease processes.

Antidepressant and nerve growth stimulating effects of exercise - a mechanism.

Yau et al. find that a hormone secreted by fat cells during exercise alleviates depression-like behaviors in mice and boosts new nerve cell synthesis in the hippocampus. The hormone, or compounds that enhance its effectiveness, are potential antidepressant drugs. I copy below their significance section and the abstract with some of the chemical details.

Significance

This study unmasks a previously unidentified functional role of adiponectin (a hormone secreted by adipocytes) in modulating hippocampal neurogenesis and alleviating depression-like behaviors. To our knowledge, this is the first report showing that adiponectin may be an essential factor that mediates the antidepressant effects of physical exercise on the brain by adiponectin receptor 1-mediated activation of AMP-activated protein kinase. Our results reveal a possible mechanism by which exercise increases hippocampal neurogenesis and also suggest a promising therapeutic treatment for depression.

Abstract

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, anti-inflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

Aging: sit less and shape up your attitude

I'm continuing to clean out my queue of aging articles that have been languishing as potential posts...

Reynolds points to two studies. In one, Swedish researchers showed that a group of 68 year old couch potatoes who spent less time sitting and more time in an exercise program had longer telomere caps at the end of their DNA (the caps shorten with aging). The interesting finding was that this was related not to the exercise, but to simply not sitting down as much. A second article reviewed a large database of Canadian adults to find that longer amounts to time spent standing correlated with lower mortality rates.

Span does a review (linking to original articles) of work showing, for example that people who hold more positive views towards aging live 7.5 years longer on average than those who think negatively about aging, and recover more quickly from disabilities. Age stereotypes have a powerful effect, people become what they think. Thinking of older age as a time when one can feel capable, active, full of life, a time of wisdom, self-realization and satisfaction, is rather different from imagining it to be a time of becoming useless, helpless or devalued. A growing body of research shows that people with the latter attitudes are less likely to seek preventive medical care and die earlier, and more likely to suffer memory loss and poor physical functioning.

One interesting bit of work shows that subliminal intervention (flashing positive about aging on a screen so briefly that the brain registers them but they are not perceived) significantly strengthened positive age stereotypes and self-perceptions of age. The abstract:

Negative age stereotypes that older individuals assimilate from their culture predict detrimental outcomes, including worse physical function. We examined, for the first time, whether positive age stereotypes, presented subliminally across multiple sessions in the community, would lead to improved outcomes. Each of 100 older individuals (age = 61–99 years, M = 81) was randomly assigned to an implicit-positive-age-stereotype-intervention group, an explicit-positive-age-stereotype-intervention group, a combined implicit- and explicit-positive-age-stereotype-intervention group, or a control group. Interventions occurred at four 1-week intervals. The implicit intervention strengthened positive age stereotypes, which strengthened positive self-perceptions of aging, which, in turn, improved physical function. The improvement in these outcomes continued for 3 weeks after the last intervention session. Further, negative age stereotypes and negative self-perceptions of aging were weakened. For all outcomes, the implicit intervention’s impact was greater than the explicit intervention’s impact. The physical-function effect of the implicit intervention surpassed a previous study’s 6-month-exercise-intervention’s effect with participants of similar ages. The current study’s findings demonstrate the potential of directing implicit processes toward physical-function enhancement over time.

Exercise protects retinas.

Gretchen Reynolds points to an article by Lawson et al. showing that the increase in blood levels of brain-derived neurotrophic factors (B.N.D.F.), known to promote neuron health and growth, apparently also raises BNDF levels in the retina. In a mouse model for retinal degeneration (vaguely analogous to human macular degeneration), exercise that raises BNDF levels inhibits the retinal deterioration caused by brief (4 hour) exposure to very bright lights.

Aerobic exercise is a common intervention for rehabilitation of motor, and more recently, cognitive function. While the underlying mechanisms are complex, BDNF may mediate much of the beneficial effects of exercise to these neurons. We studied the effects of aerobic exercise on retinal neurons undergoing degeneration. We exercised wild-type BALB/c mice on a treadmill (10 m/min for 1 h) for 5 d/week or placed control mice on static treadmills. After 2 weeks of exercise, mice were exposed to either toxic bright light (10,000 lux) for 4 h to induce photoreceptor degeneration or maintenance dim light (25 lux). Bright light caused 75% loss of both retinal function and photoreceptor numbers. However, exercised mice exposed to bright light had 2 times greater retinal function and photoreceptor nuclei than inactive mice exposed to bright light. In addition, exercise increased retinal BDNF protein levels by 20% compared with inactive mice. Systemic injections of a BDNF tropomyosin-receptor-kinase (TrkB) receptor antagonist reduced retinal function and photoreceptor nuclei counts in exercised mice to inactive levels, effectively blocking the protective effects seen with aerobic exercise. The data suggest that aerobic exercise is neuroprotective for retinal degeneration and that this effect is mediated by BDNF signaling.