As obesity increases in aging Western populations, frailty – which is exacerbated by obesity – is becoming a greater health concern and a major healthcare cost.
Now, researchers report July 3 in the journal Cell Metabolism that combining aerobic exercise and resistance training helps elderly obese individuals preserve muscle mass and reverse frailty as they work to lose weight.
Based on a small clinical trial, the study showed that patients who completed these exercises had increased muscle protein synthesis and preserved muscle quality compared to control groups.
In a previous study, Dennis T. Villareal, professor and geriatric endocrinologist at Baylor College of Medicine, hypothesized that resistance training would best complement weight loss for improving physical function in older obese adults.
Study participants took part in a weight-management program and were randomly assigned aerobic workouts, resistance training or a combination of both.
Villareal and colleagues were surprised to find that combined aerobic and resistance training improved cardiovascular fitness to the same extent as aerobic training alone and improved muscle strength to the same extent as resistance training alone.
They reported in the New England Journal of Medicine in May 2017 (DOI: 10.1056/NEJMoa1616338) that combined aerobic and resistance training resulted in the greatest improvement in physical function and reducing frailty in older obese.
However, it was unclear how obese older adults in particular benefitted from aerobic workouts geared toward cardiovascular fitness combined resistance training.
In the Cell Metabolism study, the researchers used molecular and cellular techniques to assess changes in their muscle protein synthesis and myocellular quality to examine the mechanisms underlying the obese older adults’ improvement in physical function and preservation of lean body mass.
A subset of participants – 47 of the original 160 – agreed to undergo muscle biopsies before and after six months of lifestyle interventions to see how their muscle tissue was affected.
The participants were men and women that averaged between 69 and 72 years of age and more than half were Hispanic/Latinx. Aerobic activities included treadmill walking, stationary cycling, and stair climbing, with participants exercising at approximately 65% of their peak heart rate; resistance training consisted of 1 to 3 sets of 8 to 12 reps on nine upper-body and lower-body weight-lifting machines.
“Our findings indicated that despite negative energy balance from diet-induced weight loss, exercise training in older adults with obesity helps to preserve muscle mass, improve physical function and reduce frailty,” Villareal says.
The study found that the participants’ muscle protein synthesis rate increased more with resistance training and combined aerobic-resistance exercise than in the control group.
The combined aerobic-resistance exercise was also associated with lower expression of genes associated with muscle atrophy and the best preservation of muscle growth regulators, which the researchers hypothesized could also play a role in promoting muscle mass preservation and improvement in physical function in that group.
In the elderly obese, combined aerobic and resistance exercise is superior to either mode independently for maintaining muscle mass during weight-loss therapy, he says. Aerobic and resistance training is the most effective strategy and therefore, Villareal notes, “the best approach.”
The population age 65 and older is expected to more than double between 2012 and 2060, from 43.1 million to 92 million [1].
The continuing increase in the older population has generated interest toward investigations of older adults who are “frail”. Frailty is a state of vulnerability that carries an increased risk for adverse outcomes [2]; it can be viewed as a transition phase in older people between good health and poor health.
Frail older adults are less capable of tolerating the stress of medical illness, hospitalization, and immobility. Common signs and symptoms are fatigue, weight loss, muscle weakness, and progressive decline in function. Frailty is more prevalent in older people and in those with multiple medical conditions.
Concomitant with age, there is decline in voluntary physical activity which is associated with decreases in numerous measures of exercise capacity including peak oxygen consumption (VO2pea), muscle strength, and fatigability which ultimately leads to frailty [3].
ecently it has been recognized that most older adults who are obese also meet criteria for frailty because of decrease muscle mass and strength that occurs with aging (sarcopenia) and a need to carry greater body mass due to obesity [4].
Because frailty increases the risk for loss of functional independence and decrease in quality of life, the identification of cost-effective interventions to prevent or ameliorate frailty is one of the most important public health challenges.
Accordingly, exercise may be an effective strategy to prevent and treat frailty as it can target four of the five commonly used criteria: weakness, low physical activity, slowed motor performance, and poor exercise tolerance [5].
Frailty is not a contra-indication to physical activity, rather it maybe one of the most important indications to prescribe physical exercise. Longitudinal studies have demonstrated that regular physical activity extends longevity and reduces the risk of physical disability.
In fact, cardiorespiratory fitness has been found to be a significant mortality predictor in older adults, independent of overall or abdominal obesity [6].
In more than 10,000 older adults participating in the Established Populations for Epidemiologic Studies of the Elderly (EPESE studies) an almost two-fold increased likelihood of dying without disability was found among those most physically active compared to those who were sedentary [7].Go to:
Aerobic endurance training
After age 30 y, aerobic capacity, often measured as VO2peak declines with age and contributes to a decrease in the older adult’s ability to perform activities of daily living.
This is largely due to three major causes: 1) a decline in the ability of the cardiopulmonary system to deliver O2 2)a decline in the ability of the working muscle to extract O2, and 3) a decline in metabolic muscle mass and parallel increase in metabolically inactive fat mass [3].
Indeed, probably one of the most notable effects of endurance training is on VO2peak which is an important determinant of frailty in older adults [4]
The improvement in VO2peak with endurance exercise training would be thought to reduce frailty in older adults and thus counter the decline in VO2peak with aging and physical inactivity.
Whereas VO2peak declines ~1%/year in non-training individuals [8] this decline is ~0.5%/years in master athletes who participate in aerobic activities [3].
Another important adaptation to endurance exercise training is an increase in muscle oxidative capacity, which results in fatigue resistance or increased muscle endurance. In an interventional trial of 64 frail older men and women, a nine month program of strength training and walking exercise at 78% of peak heart rate increased endurance by improving VO2peak by ~14% [9]. A similar exercise program for 12 months in 107 frail obese older men and women also increased VO2peakby ~10% [10].
On the other hand, in healthy 77–87 years old, nine months of endurance training at 83% of peak heart rate increased VO2peak by 15%, as compared to increased VO2peak by 24–30% in healthy 60 to 71-yr-old, indicating that the adaptations in aerobic power may be attenuated in advancing age [11].
Data from met analyses [12] also showed that endurance training may help to conserve fat free mass (FFM) during weight loss, although it is probably less effective than resistance exercise. We recently reported that compared to weight loss induced by diet, weight loss induced by aerobic exercise preserved lower extremity muscle mass (measured by magnetic resonance imaging) and physical work capacity, although the amount of exercise was large [13].Go to:
Progressive resistance training
It is well known that muscle strength and mass decreases with advancing age. A 30% reduction in strength between 50 and 70 years of age is generally found, with muscle strength losses being most dramatic after age 70 [14]. Most of the decline in strength can be explained by selective atrophy of type II muscle fibers and the loss of neuronal activation. Based on body composition techniques such as DXA and CT scan, the relative annual decline in muscle mass was estimated to be between −0.64 and −1.29% per year for older men and −0.53 and −0.84% per year for older women [15].
Although decline in muscle quality also contributes, several studies have found that the decline in strength in the older adult is primarily due to loss of muscle quantity with age. Several studies have shown that resistance exercise training increases muscle mass and thus muscle strength in both younger and older adults.
However, the response to resistance training appears to be attenuated in older adults with mobility limitations or other co-morbidities.
In healthy older adults, four months of progressive resistance training increased muscle mass by 16 to 23%, whereas it increased muscle mass by 2.0–9% in frail older adults [10, 16–18]
Other studies showed that the gain in FFM in older women and men was only ~58% of that for younger men and women in response to resistance training [19].
Nonetheless, resistance training still has been found to significantly increase strength in older men and women. Several studies have demonstrated that these changes can occur even in the late stages in life [20, 21].
Indeed, based on two recent systemic reviews of randomized controlled trials (RCT) involving resistance training in older adults, it was concluded that resistance training results in significant improvement in muscle strength in older adults [22, 23].
These reviews included studies in both healthy and older adults. Of particular interest is that In frail institutionalized patients, Fiatarone et al demonstrated that 10 weeks of resistance exercise training increased muscle strength by ~113% as compared to ~3% in nonexercising subjects [16].
Moreover, our group has shown that in frail older men and women, resistance training added to diet reduced FFM loss (from 3.5 kg to 1.8 kg) during voluntary weight loss and increased both upper and lower extremity muscle strength (by 17–43%) despite FFM loss [24].
With respect to aspects of functional limitations, resistance training has been shown to improve gait speed in healthy and frail elders (weighted mean differences = 0.07 m/s based on 14 trials; n=798)[22].
Specifically, in frail older adults living in the nursing home and in the community, ten weeks of resistance training has been shown to significantly improve gait speed [16].Go to:
Combined aerobic and resistance training
Not only the physiologic adaptations to aerobic exercise and to resistance exercise are distinctly different but also both types of exercise target specific components of frailty. Therefore, the few exercise interventions conducted in frail older populations have mostly used combined aerobic and resistance exercise.
A nine month RCT intervention of aerobic and resistance exercise concomitantly improved scores in the VO2peak (95% confidence bounds [CI] 0.9 to 3.6 mL/kg/min) and modified physical performance test (95% CI 1.0 to 5.2 points) [25].
In addition, a recent 12 month RCT of aerobic and resistance exercise also improved scores in the VO2peakand modified physical performance test in frail obese older adults, which were additive to the effects of diet-induced weight loss [10].
Finally, the Lifestyle Intervention and Independence for Elders (Life) pilot study also reported that a 12 month program of walking, resistance exercise, and flexibility training resulted in a clinically meaningful improvement of physical performance as assessed by using the Short Physical Performance Battery [26].
This study also presented promising evidence on the effectiveness of exercise in the prevention of the disability in walking as assessed by the capacity to complete a 400 meter work.
Effect on frailty as an outcome measure
Most exercise intervention trials studied the effects on features of frailty and the adverse outcomes of frailty. T
here have been relatively few studies designed to determine whether physical exercise can reverse frailty (frail reverse to nonfrail) or if older adults can convert from a greater state of frailty to a lesser state of frailty with exercise.
The Frailty Intervention Trial (FIT) study examined whether a multifactorial intervention that included balance, strength, and endurance exercise could reduce frailty and improve mobility [27].
After 12 months of the intervention, there was a lower prevalence of frailty in the intervention group compared with the control group (between group difference 14.7%) which was associated with a significant improvement in the Short Physical Performance Battery (between group difference 1.44 pts), suggesting that it is possible to successfully “treat” frailty.
Molecular and cellular mechanisms underlying exercise training
Aging and physical inactivity are associated with increased levels of chronic inflammation. Inflammatory cytokines have direct catabolic effects on skeletal muscle:
Tumor necrosis factor-alpha (TNF-α) suppresses muscle protein synthesis (MPS) [28], while Interleuken-6 (IL-6) inhibits the anabolic effects of insulin-like growth factor-1 (IGF-1) [29].
These cytokines also induce insulin resistance, which contributes to sarcopenia and frailty by reducing MPS. High concentrations of TNF-α or IL-6 are associated with lower muscle mass or strength and mobility disability [30] and high IL-6 and low IGF-1 levels contribute synergistically to impaired mobility [31].
Accordingly, an important mechanism by which exercise training reduces frailty is by suppressing muscle inflammation and promoting anabolism which leads to an increase in MPS (Figure 1).
We previously reported that in frail obese older adults 12 weeks of exercise (aerobic and resistance ) but not 12 weeks of weight loss (~7% reduction) decreased IL-6 and TNF-α and increased mechano growth factor mRNA of skeletal muscles, which was associated with positive effects on functional status [32].
Moreover, in these frail obese older adults, a multicomponent exercise program increased the mixed muscle protein fractional synthesis rate in the basal, postabsorptive state without affecting the magnitude of muscle protein anabolic response to feeding [33].
These changes in muscle protein anabolism were accompanied by increases in FFM, appendicular lean body mass, strength, and VO2peak, all of which are important determinants of frailty.
There appears to be sexual dimorphism in muscle protein anabolism in that 1) older women have greater MPS rate in the basal state but less anabolic response to mixed meal than older men [34] and 2) older women have less MPS rate increase in response to exercise training in the basal state than older men [35].
These findings may explain not only the lower muscle mass in older women but also perhaps the need for greater exercise stimuli to achieve the same anabolic response seen in older men [36].
Figure 1
Theoretical framework for the molecular and cellular mechanisms by which physical exercise ameliorates frailty in older adults. Abbreviations: MGF, mechano growth factor; TNF-α, Tumor necrosis factor-alpha, IGF-1, Insulin-like growth factor 1; ADL, activities of daily living
More information: Cell Metabolism, Colleluori et al.: “Aerobic Plus Resistance Exercise in Obese Older Adults Improves Muscle Protein Synthesis and Preserves Myocellular Quality Despite Calorie Restriction” https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30311-0 , DOI: 10.1016/j.cmet.2019.06.008
Journal information: Cell Metabolism
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