A High-Fat Diet Aggravates the Age-Related Decline in Skeletal Muscle Structure and Function

Hans Degens; Anandini Swaminathan; Jason Tallis


Exerc Sport Sci Rev. 2021;49(4):253-259. 

In This Article

The Effects of HFD and Aging on Skeletal Muscle

Even though the absolute force and power-generating capacity of postural and locomotory muscles may be higher in the overweight and obese, they are lower when expressed per body mass[15] or muscle mass[10,16] in both humans and rodents. These observations indicate that, similar to aging, overweight and obesity are accompanied by a lower muscle quality.[6] Part of the reduced muscle quality may well be attributable to the accumulation of IMCL in both human[17] and mouse muscle, irrespective of fiber type.[18,19]

Lifestyle factors, such as physical activity levels, comorbidities, genetic differences, and diet, can have a significant impact on muscle mass and quality in old age.[20] Previously, we discussed that the effects of overweight and an HFD on skeletal muscle are strikingly similar to the effects of aging, and the question arises whether an HFD and overweight accelerate or aggravate muscle aging.

As discussed previously, the increased loading of the antigravity muscles in overweight and obese individuals induces an increase in their force and power-generating capacity.[6] In older adults, however, such an increase in force and power-generating capacity occurs less frequently,[16,21] and some studies even report a lower absolute force-producing capacity.[21] The disparity in response between young-adult and old obese groups may in part be explained by an age-related reduction in myogenesis,[2] limiting the adaptions to elevated loading imposed by the higher body mass in overweight or obese individuals.

Undoubtedly, the lower force to body mass or regional lean mass ratio in obese than in nonobese older adults[16,21] contributes to the compromised ability to perform daily life activities.[22] Even in the absence of overweight or obesity, a high level of intermuscular adipose tissue was associated with lower muscle specific power and mobility limitations in older people.[11] Not only do older women have a lower muscle force-to-body mass ratio, but they may also experience an accelerated decline in strength and muscle volume compared with nonobese women.[16] This further accentuates the poorer muscle function with increasing age and puts them at risk to cross a disability threshold earlier than nonobese women. It is interesting to note, however, that the age-related reduction in specific force was slower than in nonobese women.[16] We have no explanation for this attenuated age-related decline in muscle quality, but it corresponds with the observation of an HFD-induced decline in specific power and force in the soleus and extensor digitorum longus (EDL) muscles in young-adult[23] but not old mice.[10] Perhaps IMCL accumulation, as seen in mouse muscle fibers,[19] results in a rapid decline in muscle quality via mechanisms discussed later that subsequently diminishes when the muscle storage capacity of IMCL is saturated in young-adult mice. In old mice, the age-related reduction in specific tension caused by other mechanisms[2] may mask those induced by a HFD.

The accelerated age-related decline in muscle volume and strength (but slower decline in specific force as discussed previously) in obese women[16] may indicate that the detrimental effects of overweight and an HFD are more pronounced in old than in young-adult age. A first indication that this may be the case comes from the observation in mice where HFD-induced increases in body mass, BMI, and IMCL accumulation occur earlier in old than in younger animals,[19] which may cause an earlier onset of muscle dysfunction in old animals. Indeed, an HFD caused diaphragm dysfunction, but, as discussed previously, surprisingly not so in the soleus and EDL muscles of old mice,[10] even though all muscles had a similar degree of IMCL accumulation.[19]

Longer duration of HFD (20 months) led to a lower specific tension than that seen in age-matched lean mice, suggesting that HFD aggravates muscle dysfunction also in old age, probably partly attributable to IMCL accumulation.[18] These observations in mice suggest that the effects of HFD and aging are synergistic. The potential significance of an elevated susceptibility of IMCL accumulation for older people is illustrated by the observation that the lower specific power of type I fibers in obese than in nonobese older people was related to a higher IMCL content.[24]

A (nonexhaustive) summary of the impact of HFD in rodents is given in the Table. Overall, the evidence suggests that HFD consumption 1) exacerbates the age-related decline in muscle function and 2) that there is an age-related increase in susceptibility of HFD-induced IMCL accumulation and rise in body mass and BMI. Such a synergistic effect of aging and obesity is likely to contribute to poor health outcomes, reduced physical function, and poorer quality of life. Indeed, compared with normal-weight counterparts, sarcopenic obese people are at a greater risk of metabolic syndrome, cardiovascular disease, diabetes, and all-cause mortality.[27]