Blunting of adaptive responses to resistance exercise training in women over 75 y

Abstract

Background

It is unclear how aging affects adaptive responses to resistance exercise training (RET), especially in women. We hypothesized that (i) increases in muscle mass and function after RET would be blunted in older women, and (ii) reduced ‘pro-anabolic’ changes in gene expression after a single bout of RE may underlie the blunting.

Methods

Muscle biopsies were obtained from 9 older (76–82 y) and 16 younger (19–30 y) women at rest and 2.5 h after RE (6 × 20 quadriceps maximal voluntary contractions (MVCs)) for measurement of select anabolic (e.g. IGFs, MyoD) and catabolic (e.g. MAFBx, MuRF-1) transcripts by RT-PCR. Thereafter participants undertook a supervised program of RET (4 × 15 MVCs 3× wk/12 wk). We measured knee extensor muscle volume, fatty infiltration, and mechanical muscle quality before and after RET.

Results

Before RET, older women were ~ 30% weaker (MVC 208 vs. 297 N) and had ~ 40% less quadriceps muscle (0.97 vs. 1.54 L) with greater fatty infiltration (14% vs. 10%). The most notable difference in mRNA expression after RE was for regulated in development and DNA damage response 1 (REDD1) (an endogenous suppressor of mammalian target of rapamycin (mTOR) signaling), which was depressed (− 80%), but only in young women. Moreover, adaptive responses to RET were blunted in older women with respect to increases in muscle volume (+ 2.5% (old) vs. + 6.2% (young)) and strength (+ 16% (old) vs. + 27% (young)).

Conclusions

Adaptations to RET are markedly blunted in older women, perhaps in-part due to the inability to downregulate REDD1 and thus upregulate mTOR signaling after RE.

Introduction

The beneficial effects of resistance exercise training (RET) in terms of increasing muscle mass and function have been demonstrated even in very elderly people (Fiatarone et al. 1990). However it is unclear whether older muscles are as responsive as younger muscles, i.e., does aging blunt adaptive responses to RET (i.e., increases in strength and/or hypertrophy)? Of the few studies which have included a comparison between younger and older adults, greater (Kosek and Bamman 2008), similar (Ivey et al. 2000) or less (Welle et al. 1996) muscle hypertrophy after RET has been reported in the older participants compared with the young. In agreement with the latter concept of blunted muscle hypertrophy (Welle et al. 1996), RET failed to increase type I fiber CSA in older adults compared with hypertrophy of both type I and type II fibers in a young adults (Martel et al. 2006). Also, one of us with other workers, has previously reported that increases in muscle protein synthesis after a single bout of resistance exercise (RE) are blunted in older men (Kumar et al. 2009) which may explain reductions in muscle hypertrophy after RET. Likewise, it is unclear how aging affects functional gains associated with RET. For example, increases in strength were greater in older muscles for knee flexion, lower for elbow flexion but not significantly different for knee extension when compared with younger muscles (Welle et al. 1995). In another study, the percentage change of isokinetic knee extensor peak torque after 9 wk of RET was not different between old and young individuals (Lemmer et al. 2000). Unfortunately, the number of elderly participants (i.e., those aged ≥ 75 y in whom functional decline accelerates (Svanborg 1988)) included in the studies described above are so few as to make it difficult to confirm the existence of a difference in the ‘trainability’ between older (> 75 y) and young muscles. As such this variability may simply relate to poor perspicacity of sarcopenic status. Furthermore, sex differences in power/weight indicate that women are particularly at risk (Young 1997), yet women are collectively under-represented in studies of exercise training in old age.

Adaptive capacity to RET depends upon transient changes in gene expression and anabolic signaling such that repeated bouts of resistance exercise (RE) can result in accumulation of mRNA and increases in translation and content of the encoded protein (Neufer and Dohm 1993). Therefore, it is possible that altered changes in anabolic signaling and/or gene expression after RE may contribute to the blunted adaptive capacity for RET in older people. Indeed, the existence of a coupling between gene responses or the phosphorylation status of regulatory anabolic signaling pathway proteins after a single bout of RE with the resultant adaptations to RET has been previously investigated (Baar and Esser, 1999, Bamman et al., 2007, Dennis et al., 2009). For instance, the degree of ribosomal S6 kinase phosphorylation after a bout of RE was associated with the hypertrophic response to RET (Baar and Esser 1999). Also, IGF-1 mRNA expression 24 h after RE was significantly associated with muscle hypertrophy after training in men and women up to 75 y (Bamman et al. 2007). Alternatively, a more recent but uncontrolled study showed no association between IGF-1 72 h after RE and hypertrophy after RET in ‘younger’ old men (mean age 68 y) (Dennis et al. 2009). Nonetheless, the latter study did report a significant association between myostatin downregulation 72 h after RE and muscle hypertrophy after RET. Interestingly, previous research has also shown that the capacity to downregulate myostatin (Kim et al., 2005a) and upregulate myogenin (Kim et al., 2005b) mRNA expression after RE is reduced in older individuals. In contrast, more recently a study of very elderly women 80–89 y showed only modest evidence of differences compared with young women with respect to myogenic regulatory factor mRNA responses (including myogenin and myostatin) after RE (Raue et al., 2006, Kim et al., 2005a, Kim et al., 2005b). Clearly further work is needed to define how acute changes in gene expression relate to adaptation to RET.

To fill these gaps, our objectives were to compare baseline muscle characteristics and anabolic responsiveness of younger (~ 25 y) and older (> 75 y), overtly sarcopenic women in terms of: (i) RE-induced changes in the expression of target genes linked to anabolic and catabolic processes, and (ii) changes in muscle strength, volume and mechanical quality after RET using state-of-the-art MR imaging. We hypothesized that there would exist clear maladaptation to RET in sarcopenic women (e.g. blunted hypertrophy) and this would be associated with reduced ‘pro-anabolic’ changes in gene expression after a single bout of RE.