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

Greig, Carolyn; Gray, Calum; Rankin, Debbie; Young, Archie; Mann, V.; Noble, Brendon; Atherton, Philip J.

doi:10.1016/j.exger.2011.07.010

Cited by 85 publications

(81 citation statements)

References 39 publications

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“…Many studies have focused on the role of REDD1 and/or REDD2 in repressing mTORC1 signaling under conditions of cell stress (13,19,41), with many fewer assessing their role under physiological conditions. However, recent reports have demonstrated an inverse correlation between changes in mTORC1 signaling and REDD1 and/or REDD2 expression in skeletal muscle in response to fasting and refeeding (43) as well as after a bout of resistance exercise (16,17,25). The present study extends these observations to show that elevated REDD2 mRNA expression in 9-and 18-mo-old rats is associated with an attenuation of nutrient-induced activation of mTORC1 signaling.…”

Section: Discussionsupporting

confidence: 78%

REDD2 expression in rat skeletal muscle correlates with nutrient-induced activation of mTORC1: responses to aging, immobilization, and remobilization

Kelleher

Pereira

Jefferson

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Kelleher AR, Pereira SL, Jefferson LS, Kimball SR. REDD2 expression in rat skeletal muscle correlates with nutrient-induced activation of mTORC1: Responses to aging, immobilization, and remobilization. Am J Physiol Endocrinol Metab 308: E122-E129, 2015. First published November 18, 2014; doi:10.1152/ajpendo.00341.2014.-In a previous study (Kelleher AR, Kimball SR, Dennis MD, Schilder RJ, and Jefferson LS. Am J Physiol Endocrinol Metab 304: E229 -236, 2013.), we observed a rapid (i.e., 1-3 days) immobilization-induced repression of mechanistic target of rapamycin complex 1 (mTORC1) signaling in hindlimb skeletal muscle of young (2-mo-old) rats that was associated with elevated expression of regulated in development and DNAdamage response (REDD) 1 and REDD2. The present study extends that observation to include an assessment of those parameters in soleus muscle of the immobilized hindlimb of various-aged rats as well as in response to remobilization. Male Sprague-Dawley rats aged 2, 9, and 18 mo were subjected to unilateral hindlimb immobilization for 7 days, whereas one group of the 9-mo-old animals underwent 7 days of remobilization. Soleus muscle mass-to-body mass ratio declined with age, with the loss of muscle mass following hindlimb immobilization being inversely proportional to age. Compared with 2-mo-old rats, the older rats exhibited reduced mTORC1 signaling in the nonimmobilized limb in association with elevated REDD2, but not REDD1, mRNA expression. In the 2-mo-old rats, 7 days of hindlimb immobilization attenuated mTORC1 signaling and induced REDD2, but not REDD1, mRNA expression. In contrast, hindlimb immobilization did not further attenuate the age-related reduction in mTORC1 signaling nor further enhance the age-related induction of REDD2 mRNA expression in 9-and 18-mo-old rats. Across ages, REDD1 mRNA was not impacted by immobilization. Finally, remobilization elevated mTORC1 signaling and lowered REDD2 mRNA expression, with no impact on REDD1 gene expression. In conclusion, changes in mTORC1 signaling associated with aging, immobilization, and remobilization were inversely proportional to alterations in REDD2 mRNA expression. anabolic resistance; casting; atrophy; DDIT4l; disuse LOSS OF SKELETAL MUSCLE MASS and function in the elderly leads to increased risk of falls and fractures, physical frailty, and increased morbidity and mortality (11,39,53). A period of inactivity (e.g., limb immobilization, bed rest, etc.) worsens the problem, since it leads to acute skeletal muscle atrophy (52). Both age-and inactivity-induced muscle atrophy are thought to be in large part a consequence of the development of resistance to nutrient (particularly amino acids)-induced stimulation of muscle protein synthesis (42,49). In young adult humans (e.g., ϳ25 yr old), muscle protein synthesis is stimulated in response to consumption of relatively small quantities (e.g., 7-10 g) of essential amino acids, whereas in older adults (e.g., ϳ65 yr old) a comparable amount of amino acids is ineffective (31, 32). However, inges...

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Section: Discussionsupporting

confidence: 78%

REDD2 expression in rat skeletal muscle correlates with nutrient-induced activation of mTORC1: responses to aging, immobilization, and remobilization

Kelleher

Pereira

Jefferson

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…Age-dependent responsiveness to resistance-type training is well documented for extreme age groups. Elderly are capable of responding to training with gains in muscle mass and performance but to a lesser extent compared with that of young adults [4,5,16,17]. For muscles of old rats exposed to the SSC protocol utilized in the present and previous studies, SSC-induced increases in muscle mass were blunted and performance gains were not observed [8,18,19].…”

Section: Discussionmentioning

confidence: 57%

“…Age-dependent alterations in response to chronic exposure to contractions have been observed for human subjects and animal models previously [4,5,8,10]. However, these studies were limited in the number of age groups studied.…”

Section: Discussionmentioning

confidence: 99%

“…A substantial amount of research has been focused on comparing two age groups, typically an old age group vs a much younger age group, in regards to age-related deficiencies in performance [4,5,8,10,16,17]. Based on the current findings, additional focus should be dedicated to studies which compare additional intermediate age groups to identify key regulatory factors and appropriate SSC regimes to account for maturationand aging-related alterations in muscle adaptive capacity.…”

Section: Aging and Disease • Volume 7 Number 4 August 2016 12mentioning

confidence: 99%

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Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats

Rader¹,

Layner²,

Triscuit³

et al. 2016

Aging and disease

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Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 ± 8% and 27 ± 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 ± 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

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“…Importantly, such hyperemic responses also seem to be diminished in ageing (13,25), which may contribute to reduced performance and maladaptation to exercise training in older age (16). In the present study we elected to measure LBF during the recovery period from exercise, which reflects the "remodeling" period [e.g., where muscle protein turnover is heightened (19)].…”

Section: Discussionmentioning

confidence: 99%

Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise

Phillips

Williams

Atherton

et al. 2012

Journal of Applied Physiology

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I, Rennie MJ. Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise. J Appl Physiol 112: 347-353, 2012. First published October 13, 2011 doi:10.1152/japplphysiol.01031.2011.-One manifestation of age-related declines in vascular function is reduced peripheral (limb) blood flow and vascular conduction at rest and in response to vasodilatory stimuli such as exercise and feeding. Since, even in older age, resistance exercise training (RET) represents an efficacious strategy for increasing muscle mass and function, we hypothesized that likewise RET would improve age-related declines in leg blood flow (LBF) and vascular conductance (LVC). We studied three mixed-sex age groups (young: 18 -28 yr, n ϭ 14; middle aged: 45-55 yr, n ϭ 20; older: 65-75 yr, n ϭ 17) before and after 20 wk of whole body RET in the postabsorptive state (BASAL) and after unilateral leg extensions (6 ϫ 8 repetitions; 75% 1 repetition maximum) followed by intermittent mixed-nutrient liquid feeds (ϳ6.5 kJ·kg Ϫ1 ·30 min Ϫ1 ), which allowed us to discern the acute effects of feeding (nonexercised leg; FED) and exercise plus feeding (exercised leg; FEDEX) on vascular function. We measured LBF using Doppler ultrasound and recorded mean arterial pressure (MAP) to calculate LVC. Our results reveal that although neither age nor RET influenced BASAL LBF, age-related declines in LBF responses to FED were eradicated by RET. Moreover, increases in LBF after FEDEX, which occurred only in young and middle-aged groups before RET (ϩ73 Ϯ 9%, and ϩ90 Ϯ 13%, P Ͻ 0.001, respectively), increased in all groups after RET (young ϩ78 Ϯ 10%, middle-aged ϩ96 Ϯ 15%, older ϩ80 Ϯ 19%, P Ͻ 0.001). Finally, RET robustly improved LVC under FASTED, FED, and FEDEX conditions in the older group. These data provide novel information that supports the premise that RET represents a valuable strategy to counter age-related impairments in LBF/LVC. circulation; nutrition; muscle HUMAN AGEING is associated with decreased arterial compliance, which leads to hypertension and coronary artery disease (10,11,20) such that cardiovascular disease-related morbidity and mortality increase markedly with age. Declines in peripheral (i.e., limb arterial) blood flow and increases in vascular resistance are one such characteristic manifestation of cardiovascular ageing. For example, Donato et al. (13) reported that older individuals exhibit 20 -30% lower resting, postabsorptive limb blood flow and a ϳ50% decrease in leg vascular conductance (LVC) compared with younger individuals. Such age-related changes are purported to contribute to the metabolic syndrome, a major precursor to atherosclerotic disease in humans that encompasses hyperinsulinemia, dyslipidemia, and hypertension (20).Intriguingly, declines in peripheral blood flow with ageing are not restricted to postabsorptive periods but are also observed when subjects are challenged with vasodilatory stimuli, such as food intake (31) and exercise ...

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

Cited by 85 publications

References 39 publications

REDD2 expression in rat skeletal muscle correlates with nutrient-induced activation of mTORC1: responses to aging, immobilization, and remobilization

REDD2 expression in rat skeletal muscle correlates with nutrient-induced activation of mTORC1: responses to aging, immobilization, and remobilization

Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats

Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise

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