Nutrition Across the Lifespan for Healthy Aging Proceedings of a Workshop (2017) / Chapter Skim
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4 Changes in Organ Systems Over the Lifespan
4 Changes in Organ Systems Over the Lifespan
Pages 37-86
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From page 37... ...
First, focusing on the cardiovascular system, Tamara Harris, senior investigator and chief, Interdisciplinary Studies of Aging Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, emphasized that separating cardiovascular disease from aging-related cardiovascular change is difficult, as both can lead to the same end-stage heart disease. She highlighted two age-associated cardiovascular changes in particular -- atrial fibrillation and hypertension -- both of which are common in old age and have unsettled clinical issues.
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From page 38... ...
Finally, Rafael de Cabo, senior investigator, chief of the Translational Gerontology Branch, and chief of the Experimental Gerontology Section in the Aging, Metabolism, and Nutrition Unit, National Institute on Aging, NIH, described several studies in which scientists have been able to alter both the onset and the progression of aging in laboratory animals by restricting daily total caloric intake. He discussed how efforts to identify the underlying mechanisms have led to the identification of molecular targets that can be activated or deactivated by pharmacological compounds to produce the same effects, but without actual caloric restriction.
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From page 39... ...
. But separating cardiovascular disease from aging-related cardiovascular change is difficult, she said, partly because both cardiovascular risk factors (e.g., dyslipidemia, hypertension, diabetes, smoking, obesity)
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From page 40... ...
. The consequences of cardiac aging, she explained, are that cardiac output falls as people exercise, the ability to increase heart rate in response to stress declines, aortic volume and systolic blood pressure increase (but with no change in resting heart rate)
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From page 41... ...
The leading risk factor for atrial fibrillation is increased age, Harris reported, which she said is believed to lead to fibrosis of the electrical conducting system in the heart. Other risk factors for atrial fibrillation include hypertension, diabetes, heart failure, valvular heart disease, and myocardial infarction.
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From page 42... ...
However, she noted, this recommendation was issued before findings from the Systolic Blood Pressure Intervention Trial (SPRINT) were published and before a recent meta-analysis showed that reducing blood pressure below current recommended levels further decreases the risk of heart disease, and that there is no threshold below which lowering blood pressure does not provide this benefit (Ettehad et al., 2016)
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From page 43... ...
cholesterol, total cholesterol, systolic blood pressure, smoking, and diabetes among individuals aged 50-54 markedly affect the estimated 10-year risk of cardiovascular disease (Mozaffarian et al., 2016)
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From page 44... ...
She characterized this high prevalence as "amazing." She pointed out that even in midlife, as many as 54-55 percent of adults aged 55-64 have high blood pressure. She described high blood pressure as a chronic condition that increases with age in the United States and other Western countries.
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From page 45... ...
Kris-Etherton described a study that examined the relative risk of various risk factors for cardiovascular disease in adulthood among participants in four different studies of children aged 3-18 who were overweight or obese in childhood. Juonala and colleagues (2011)
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From page 46... ...
. She concluded that, given the importance of controlling risk factors for cardiovascular disease in children to lower cardiovascular disease risk later in life, "we have a long way to go." In her opinion, added sugar is one constituent of the diet on which "we can really have an impact." She added that children aged 2-5 are consuming
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From page 47... ...
Additionally, Harris noted that the first generation of individuals who have had their blood pressure treated are now entering old age. She said it will be interesting to see what happens to the incidence of cardiovascular disease as this population continues to age.
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From page 48... ...
Bone mass begins a slight decline following adolescence, she said, and the decline accelerates during menopause among women and more gradually among men. Peak bone mass is important, Weaver asserted, because of its relationship to the risk of osteoporotic fracture, with a 5-10 percent difference in peak bone mass resulting in a 25-50 percent difference in hip fracture risk later in life (Heaney et al., 2000)
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From page 49... ...
The long bones increase in both length and diameter; their increase in diameter, she said, confers greater strength relative to increases in their mass or density with age. This growth is partially driven, she continued, by sex steroid hormones, which increase prior to the launch of rapid bone growth that occurs around the time of onset of menarche in females.
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From page 50... ...
. Based on a systematic search of the literature since 2000, she and other members of the team identified two predictors of peak bone mass with an "A" grade for the strength of the evidence: calcium and physical activity.
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From page 51... ...
(Wright et al., 2014) , an estimated 10.2 million Americans have osteoporosis, and another 43.4 million have low bone mass.
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From page 52... ...
. She noted that clinical risk factors for osteoporosis independent of bone mass density include age over 65, low body weight, family history of fracture, and history of postmenopausal fracture (including vertebral fracture)
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From page 53... ...
. She explained that among all 68,719 postmenopausal women participating in the study no significant relationship was seen between calcium and vitamin D and hip fracture, nor were there significant relationships between calcium and vitamin D and several other outcomes (myocardial infarction, cardiovascular disease, breast cancer, and death)
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From page 54... ...
Fielding said he suspects that these trends would hold up in many other parts of the world as well. Sarcopenia Fielding believes that many mobility changes associated with aging are related to changes in skeletal muscle known as sarcopenia, which he defined as age-associated loss in muscle mass and function (see also the discussion of sarcopenia in the summary of Gordon Jensen's presentation in Chapter 3)
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From page 55... ...
Over time, however, this relationship between muscle mass and strength becomes more complex. To illustrate, Fielding cited longitudinal data from the Baltimore Longitudinal Study of Aging showing that from about age 30 onward, muscle strength (or force-generating capacity)
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From page 56... ...
(Dam et al., 2014) and the mobility implications of age-associated loss in muscle mass and function, sarcopenia as a clinical syndrome still has no broadly accepted clinical definition, consensus diagnostic criteria, or treatment guidelines.
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From page 57... ...
. Much is known about the role of physical activity and exercise interventions in the health and function of skeletal muscle, Fielding continued.
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From page 58... ...
Protein metabolism plays a central role in sarcopenia, Fielding explained, because skeletal muscle mass is regulated by the balance of protein synthesis and degradation. He mentioned that some evidence suggests that protein intake is inadequate in some older adults, while other evidence suggests that protein intake is related to change in muscle mass with aging.
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From page 59... ...
Weaver added that the combination of energy deficit and reduced protein intake affects bone as well. Johanna Dwyer, workshop participant, expressed concern that dietitians and nutritionists are not paying enough attention to sarcopenia.
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From page 60... ...
He replied that some small studies have showed that omega-3 fatty acids can increase protein synthesis and lean mass accumulation in skeletal muscle in older adults. This is just one example of what is known, he noted.
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From page 61... ...
It may be, she observed, that the olfactory epithelium in the anterior region of the nose is exposed to more irritants, pollutants, and potentially infectious agents traveling up into the nose; indeed, anatomical studies have shown more patchiness and more infiltration of respiratory epithelium in the anterior regions. In other words, Rawson said, the receptors may simply no longer be present in that part of the nose in older adults.
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From page 62... ...
Of these factors, Rawson said, she found the association between smell dysfunction and lack of regular exercise to be particularly interesting, as well as the association with having had ear tubes inserted. With regard to the biological underpinnings of olfactory dysfunction, Rawson emphasized the importance of hydration in maintaining the right composition of the olfactory mucus, which plays a key role in protecting and transporting odors across the olfactory epithelium.
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From page 63... ...
There are ways, she said, to culture human olfactory epithelial cells and study their functional characteristics in vitro. One of the more interesting recent studies on olfactory epithelium regeneration, in her opinion, demonstrated in a mouse model that telomere shortening impaired regeneration from injury, but did not affect recovery of cells under normal homeostatic conditions (Watabe-Rudolph et al., 2011)
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From page 64... ...
. People do not want to give up their teeth, she said, but unfortunately, the teeth they are keeping are unhealthy, with root decay being more common than diabetes, heart disease, mental illness, arthritis, 8 This section summarizes information presented by Dr.
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From page 65... ...
Denture wearers also have lower weights and skinfold-test results and lower levels of plasma albumin, carotenoids, and vitamin B12. In sum, Papas said, "The nutrient quality of the diet significantly goes down as you lose teeth," and this, in turn, increases the risks for stroke, coronary heart disease, and diabetes (Lara et al., 2014)
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From page 66... ...
, those who took a multivitamin or supplemented their diet with calcium experienced less severe increases in periodontal disease, and intake of both too little and too much vitamin A was detrimental. Papas said she suspected that high vitamin A intake was detrimental because of its effect on bone density.
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From page 67... ...
Individuals with periodontitis have the greatest number of microbial organisms. They have what Papas described as the "red complex," a group of bacteria that have been associated with heart disease.
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From page 68... ...
Papas replied that 20 years ago, she and colleagues examined people in 28 nursing homes and found severe dental problems. What bothers her now, she said, is that "nothing has changed." She commented on ongoing work to include oral health in the nursing curriculum so that nurses can examine patients' mouths and address these problems.
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From page 69... ...
" Davis asked. She described a recent case-control study conducted on a "Blue Zone" pocket of people living in Italy, where researchers examined the gut microbiota of healthy individuals from several different age categories, including 24 individuals aged 105-109 (Biagi et al., 2016)
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From page 70... ...
; prebiotics (i.e., nondigestible food ingredients, such as inulin and other oligosaccharides, that selectively stimulate the growth of Lactobacillus or other gut bacteria) ; synbiotics (i.e., combinations of prebiotics and probiotics, with the prebiotics serving as an energy source for the probiotics)
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From page 71... ...
; butyrate (one of the short-chain fatty acids produced by colonic bacteria upon fermentation of dietary fiber) ; and the relationship among fiber, butyrate, and colon cancer (butyrate decreases the proliferation of cancer cells and increases cancer cell apoptosis)
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From page 72... ...
. One of the most interesting examinations of the relationship between dietary fiber and microbial diversity, in Davis's opinion, is a recent animal study showing that a high-fiber diet was associated with high microbial diversity (Sonnenburg et al., 2016)
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From page 73... ...
This type of nutrient–nutrient interaction is not limited to allicin, Davis remarked. She cited the example of resveratrol, which has been shown to have a similar protective effect, and she suggested that this effect may explain the so-called French paradox, whereby red wine in combination with meat consumption protects against cardiovascular disease.
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From page 74... ...
collected data on 800 individuals, ran a computer model, and conducted a dietary intervention study, and found that differences in glycemic response to the same foods could be predicted based on information about the gut microbiome. Davis interprets these results to mean that different people respond differently to the same food.
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From page 75... ...
She explained that human milk contains bioactive components (such as human milk oligosaccharides and immune proteins) that serve non-nutritional roles, including stimulating development of the gut microbiota.
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From page 76... ...
The effect of formula on the infant microbiome, Donovan noted, depends on whether probiotics or prebiotics have been added to the formula. A Noninvasive Approach to Studying the Infant Gut Microbiome Donovan remarked that many studies of the early human gut microbiome are descriptive, with very few having examined potential mechanisms of action.
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From page 77... ...
As one example of their findings, she observed that the linear discriminate analysis identified endothelial PAS Domain Protein 1 (EPAS1) as the best gene classifier, or biomarker, of a breastfed versus formula-fed infant.
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From page 78... ...
They identified some two- and three-gene combinations that could serve as potential biomarkers of breastfeeding versus formula feeding in infants. The differentially expressed genes not only provide insight into potential mechanisms whereby human milk regulates intestinal development, but also represent potential targets for manipulation of the composition of infant formula.
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From page 79... ...
40 X(2) 30 20 10 0 FIGURE 4-6 Percentages of five phyla found in the gut microbiota of breastfed (BF)
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From page 80... ...
Janet King, workshop presenter, asked Donovan whether her finding that the gut microbiome in breastfed infants is more diverse than that of formula-fed infants may be due to the fact that breastmilk itself is diverse and, if so, what factors in breastmilk may be contributing. Donovan replied that much of the diversity in human breastmilk is diversity in the HMOs, which she said researchers have only begun to understand in the last 5-10 years.
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From page 81... ...
He then described the almost exponential increase in the prevalence of disease with increasing age and emphasized that the major risk factor for the leading causes of death (heart disease, cancer, stroke, emphysema, pneumonia, diabetes, accidents, kidney disease, Alzheimer's) is aging itself, not obesity or some other factor.
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From page 82... ...
. According to de Cabo, caloric restriction has been shown to have an effect on lifespan in every species tested.
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From page 83... ...
. He calls such compounds "caloric restriction mimetics." The goal, he explained, is to develop caloric restriction mimetics that have the same FIGURE 4-8 Change in the human survival curve over time, 1541-1991.
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From page 84... ...
In addition to caloric restriction mimetics, de Cabo mentioned several other similar strategies that have been proposed as ways to elicit the same effects as caloric restriction but without that form of restriction. These include time-restricted feeding, which involves providing food for very short periods of time; intermittent fasting, for example, eating one day, but not the next; and restriction of amino acids, such as methionine.
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From page 85... ...
a 3-month experiment in which they treated wild type and db/db (prone to diabetes) mice with either 40 percent caloric restriction or feeding every other day, both with and without exercise (running)
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From page 86... ...
showed that periodic shortterm fasting can protect against carcinogenesis and other risk factors of aging. In conclusion, de Cabo believes that in the future, more tools will be available with which to identify for whom, when, and how longevity interventions can or should be applied.
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