Muscle strength and mass have been suggested as indicators of overall health because they are established predictors of mortality and risk of NCDs:

A 2022 meta-analysis of 48 studies demonstrated an almost linear inverse dose-response relationship between muscle strength (as indicated by handgrip strength) and all-cause mortality, whereas cardiovascular and cancer mortality showed trends for a U-shaped association, meaning that very low and very high handgrip strength was not associated with reductions in risk.^[1]
A 2018 meta-analysis of 38 studies reported an inverse association between handgrip strength and knee-extension strength and risk of death.^[2]
An analysis of data from the UK biobank demonstrated a strong positive association between handgrip strength and muscle mass (measured by dual x-ray absorptiometry) and inverse associations between handgrip strength and various NCDs (e.g., obesity, sarcopenia, diabetes) and risk of cardiovascular and respiratory events.^[3]
A 2023 meta-analysis of 49 prospective studies reported an inverse association between muscle mass and death from all causes, cardiovascular diseases, cancer, and respiratory diseases.^[4]
Muscle wasting was associated with a higher risk of death from all causes, cardiovascular and respiratory diseases, and cancer.^[4]
Self-reported muscle strength was suggested as a potential screening tool to identify people at risk for NCDs.^[5]

Although the mechanism underlying the associations of muscle strength and mass with death and NCDs is not completely understood, one suggested explanation is the ability of skeletal muscle to regulate metabolism.^[6] Skeletal muscle is mostly known for its role in physical movement, posture, and breathing, but it also plays a role in glucose and amino acid metabolism. Skeletal muscle facilitates glucose uptake and transport in response to exercise and serves as a storage site for both glucose and amino acids, which are stored as protein. The amino acid reservoir from skeletal muscle can be tapped into to maintain levels of immune cells and related proteins during times of stress.^[7] This means that people with greater muscle strength and mass are less prone to insulin resistance,^[8]^[9] characteristic of metabolic diseases like type 2 diabetes. They are also more resilient to acute illness.^[10] Furthermore, in vitro (cell culture) and animal studies suggest that skeletal muscle reprograms metabolism during muscle synthesis to increase glycolysis and shift toward constructive (i.e., anabolic) metabolism (e.g., using carbon from glucose to support production of nonessential amino acids), but this phenomenon needs to be further explored.^[11]

Genetics account for a large portion of variability in muscle strength (30%–85%) and mass (50%–80%) between individuals, and GWAS studies have identified many common variants that exhibit small effects.^[12]^[13]^[14] This means that genetics have a considerable influence on an individual’s muscle strength and mass, although the role of environmental factors seem to increase with age.^[15] This doesn’t mean that someone who is dealt the worst hand of genes for muscle strength can’t improve their situation. Muscle strengthening activities like resistance training have been inversely associated with death from all causes and common NCDs, with most benefits observed at 30–60 minutes per week, and the addition of aerobic exercise further reduced risk of death from all, cardiovascular, and total cancer causes.^[16]

The study under review nicely connects the genetic basis of muscle strength and the associations of muscle strength with risk of death and NCDs. It extends previously reported associations of muscle strength with cognitive dysfunction and mental health.^[17] Genetic factors and handgrip strength have previously been found to be predictors of cognitive dysfunction^[18]^[19] and mental health,^[12]^[20] suggesting common genetic neurochemical or neurofunctional factors with muscle strength and brain function.^[21]^[22] Beyond some reported genetic correlations between handgrip strength and measures of body composition (e.g., BMI, body fat), studies on handgrip strength and BMI have previously reported controversial findings,^[12]^[23]^[24] and this study did not find an association between PGS for BMI and handgrip strength. Sex differences have been suggested to explain some of this variation, and the study under review found sex-related differences in genetically predicted handgrip strength related to cognitive disorders and BMI. On the other hand, only minor genetic differences between sexes for numerous human traits and diseases have been reported.^[25]^[26]

The authors of the study suggest that the reported associations may underestimate true associations because the UK Biobank participants have been reported to be healthier, and possibly stronger, than the general British population of the same age.^[27] It is also worth noting that the UK Biobank population was found to be older and live in less socioeconomically deprived areas than the general population, which also may limit the generalizability of the results. Moreover, some of the datasets used contain limited information on lifestyle factors that may mediate or moderate the observed associations.

Overall, this study suggests that muscle strength is a tool that can be used to predict future health issues, NCD risk, and longevity. Muscle strength shouldn’t be used alone and may not cover other related genetic and lifestyle factors, but could help build an understanding of how environmental and lifestyle factors modify an individual’s intrinsic capacity to resist disease.

Genes for stronger muscles protect against death and disease Original paper