Nutrition Across the Lifespan for Healthy Aging Proceedings of a Workshop (2017) / Chapter Skim
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3 The Spectrum of Aging and Health Over the Lifespan
3 The Spectrum of Aging and Health Over the Lifespan
Pages 19-36
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From page 19... ...
He focused most of his talk on homeostatic dysregulation, specifically dysregulation of inflammation, which he said can have "devastating" effects, including impaired mobility. Finally, Gordon Jensen, senior associate dean for research and professor of medicine and nutrition, University of Vermont Larner College of Medicine, emphasized that obesity is a much stronger predictor of all-cause mortality at younger than at older ages, and spoke about the so-called obesity paradox -- that mild obesity in the elderly is paradoxically associated with lower, not higher, mortality risk.
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From page 20... ...
Chronic oxidative stress and inflammation in young adults are in turn linked to an increased risk of metabolic disease at older ages. The Link Between Fetal Undernutrition and Increased Risk of Metabolic Disease Later in Life The first evidence linking fetal nutrition to later health came from a series of studies on the Dutch famine during World War II, which, King explained, serves as a natural study of severe food deprivation.
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From page 21... ...
They found that disease risk increased with low birth weight combined with a marked increase in childhood body mass index (BMI) from ages 3 to 11 years (Barker et al., 2002)
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From page 22... ...
Childhood outcomes among children born to obese mothers include obesity, adverse body composition, increased blood pressure, adverse lipid profile, increased inflammatory markers, and impaired insulin/glucose homeostasis. Adult outcomes include obesity, increased blood pressure, adverse lipid profile, impaired insulin/ glucose homeostasis, and premature mortality.
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From page 23... ...
, Prentice and colleagues wanted to see whether they could influence DNA methylation in the newborn by providing women with a supplement of micronutrients prior to conception and through the first trimester. To this end, King reported, they randomized Gambian women to multimicronutrient or placebo supplementation from prepregnancy to the end of the first trimester.
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From page 24... ...
She called attention to the large literature on the relationship between DNA methylation and inflammation and oxidative stress, noting that inflammation and oxidative stress may, in turn, be precursors of agingrelated metabolic diseases. Breaking the Cycle The question for King is whether this increased risk of metabolic disease can be reduced -- for example, by adding micronutrients to the diet.
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From page 25... ...
Based on a review of epidemiological studies, he and his colleagues identified four domains of aging: (1) changes in body composition, (2)
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From page 26... ...
. Yet, while obesity is proinflammatory, he reported, evidence from bariatric surgery and liposuction and the disconnect between rapid weight loss and IL-6 levels in the blood following these procedures suggests that "fat cannot be the only thing" (Klein et al., 2004)
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From page 27... ...
He and colleagues conducted what he called "the fast food study," in which they mimicked a fast food meal (a 1,000-calorie meal with saturated fat instead of polyunsatured fat) and provided study participants with either the fast food–like meal or a healthy meal.
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From page 28... ...
Ferrucci and colleagues found in a longitudinal observational study with humans that in individuals with inflammation, the amount of protein required to maintain stability of muscle mass was much greater relative to the amount required by individuals without inflammation. Moreover, he noted, those with high inflammation, regardless of their protein intake, always showed a decline in muscle mass.
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From page 29... ...
During his presentation, he said, he would "wade into an area of tremendous controversy," that is, the so-called obesity paradox, whereby mild obesity in the elderly is paradoxically associated with lower, not higher, mortality risk. Health and Mortality Outcomes Associated with Obesity Jensen said, "I sometimes think you are born, you start to have inflammation, and then it progresses the rest of your life." That said, he continued, there are many adverse health outcomes specifically associated with obesity as one ages, including premature disease, functional decline, and shortened duration of life.
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From page 30... ...
The interesting finding from this study, he said, was that the highest mortality was among those with low muscle mass who were either normal weight or overweight, and that normal-weight participants had a greater mortality risk than overweight individuals, a paradox explained partly by muscle mass. In another study of sarcopenic obesity, Jensen continued, Bea and colleagues (2015)
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From page 31... ...
In sum, he said, individuals who were underweight had a significantly greater risk of all-cause mortality, while those with overweight or mild obesity had a significantly lower risk. Thus, he explained, consistent with results of other studies, these researchers found a U-shaped relationship between BMI and all-cause mortality, with the lowest mortality risk seen among those with a BMI of 28-30 (see Figure 3-3)
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From page 32... ...
Jensen did not have time to present each analysis, but listed the multiple sensitivity analyses conducted in an attempt to bring a high level of rigor to the analysis, which included analysis of a fully adjusted model with never-smokers with no disease burden; metabolically unhealthy individuals, including all individuals meeting any diabetes criterion; metabolically healthy individuals, including only those with no metabolic risk factors; never-smokers, excluding individuals who died during the first 5 years of follow-up; all individuals, excluding those who became metabolically unhealthy during follow-up; and all individuals, excluding those who used cholesterol-lowering, diabetes, and blood pressure medications. Over the almost 11-year study period, Jensen reported, there were 2,294 deaths among the study participants.
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From page 33... ...
Of course, he added, there are many older adults who are overweight or mildly obese who are metabolically unhealthy and who do have an increased mortality risk. In Jensen's opinion, an important hypothesis to test in the future is whether these same metabolically healthy overweight and mildly obese individuals are also to some degree protected from chronic inflammation and sarcopenic obesity.
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From page 34... ...
Jensen replied that it is an important observation that some 30 percent of older adults who are overweight or have class I obesity are metabolically healthy, compared with 10 percent of those with class II or III obesity. He clarified that he was not suggesting that public health guidance regarding BMI be changed; rather, he said, "we might want to rethink how we apply it." Instead of suggesting to some older adults who are overweight and metabolically healthy that they lose weight, he observed, perhaps the focus should be on how best to preserve their quality of life with respect to flexibility, transfer, strength, and function.
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From page 35... ...
He mentioned again that in his opinion, an important hypothesis to test in the future is whether metabolically healthy overweight and obese individuals are also to some degree protected from chronic inflammation and reduced lean body mass. Physical activity could be examined in that context, he noted.
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From page 36... ...
Questions About Biomarkers of Aging Biomarkers of aging were another key focus of the discussion. In response to Kwik-Uribe's asking the panelists whether they thought any specific biomarkers warranted further evaluation, Ferrucci commented on the emergence of robust biomarkers that track chronological age, such as DNA methylation markers.
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