HEALTH NEWS

Study Title:

Muscle Aging in the Elderly

Study Abstract

Background: Reduced postprandial muscle proteolysis is mainly due to increased insulin availability. Whether rates of proteolysis in response to low physiologic doses of insulin are affected by aging is unknown.

Objectives: We tested the hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted in older subjects, together with blunted activation of Akt–protein kinase B (PKB).

Design: Groups of 8 young [mean (±SD) age: 24.5 ± 1.8 y] and older (65.0 ± 1.3 y) participants were studied during euglycemic (5 mmol/L), isoaminoacidemic (blood leucine 120 µmol/L) clamp procedures at plasma insulin concentrations of 5 and 15 µIU/mL for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of amino acid tracers), and muscle protein synthesis were measured with D5-phenylalanine and [1,2-13C2]leucine. The kinase activity of muscle Akt-PKB and the extent of phosphorylation of signaling proteins associated with the mTOR (mammalian target of rapamycin) pathway were measured before and after the clamp procedures.

Results: Basal LPB rates were not different between groups (66 ± 11 compared with 51 ± 10 nmol leucine • 100 mL leg–1 • min–1 and 30 ± 5 compared with 24 ± 4 nmol phenylalanine • 100 mL leg–1 • min–1 in young and older groups, respectively). However, although insulin at 15 µIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen in muscle protein synthesis or associated anabolic signaling phosphoproteins.

Conclusions: At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.

From press release:

Have you ever noticed that people have thinner arms and legs as they get older? As we age it becomes harder to keep our muscles healthy. They get smaller, which decreases strength and increases the likelihood of falls and fractures. New research is showing how this happens — and what to do about it.

A team of Nottingham researchers has already shown that when older people eat, they cannot make muscle as fast as the young. Now they’ve found that the suppression of muscle breakdown, which also happens during feeding, is blunted with age.

The scientists and doctors at The University of Nottingham Schools of Graduate Entry Medicine and Biomedical Sciences believe that a ‘double whammy’ affects people aged over 65. However the team think that weight training may “rejuvenate” muscle blood flow and help retain muscle for older people.

These results may explain the ongoing loss of muscle in older people: when they eat they don’t build enough muscle with the protein in food; also, the insulin (a hormone released during a meal) fails to shut down the muscle breakdown that rises between meals and overnight. Normally, in young people, insulin acts to slow muscle breakdown. Common to these problems may be a failure to deliver nutrients and hormones to muscle because of a poorer blood supply.

The work has been done by Michael Rennie, Professor of Clinical Physiology, and Dr Emilie Wilkes, and their colleagues at The University of Nottingham. The research was funded by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC) as part of ongoing work on age-related muscle wasting and how to lessen that effect.

Research just published in The American Journal of Clinical Nutrition compared one group of people in their late 60s to a group of 25-year-olds, with equal numbers of men and women. Professor Rennie said “We studied our subjects first — before breakfast — and then after giving them a small amount of insulin to raise the hormone to what they would be if they had eaten breakfast, of a bowl of cornflakes or a croissant.”

“We tagged one of the amino acids (from which proteins are made) so that we could discover how much protein in leg muscle was being broken down. We then compared how much amino acid was delivered to the leg and how much was leaving it, by analysing blood in the two situations.

“The results were clear. The younger people’s muscles were able to use insulin we gave to stop the muscle breakdown, which had increased during the night. The muscles in the older people could not.”

“In the course of our tests, we also noticed that the blood flow in the leg was greater in the younger people than the older ones,” added Professor Rennie. “This set us thinking: maybe the rate of supply of nutrients and hormones is lower in the older people? This could explain the wasting we see.”

Following this up led Beth Phillips, a PhD student working with Professor Rennie, to win the Blue Riband Award for work she presented at the summer meeting of The Physiological Society in Dublin. In her research Beth confirmed the blunting effect of age on leg blood flow after feeding, with and without exercise. The team predicted that weight training would reduce this blunting. “Indeed, she found that three sessions a week over 20 weeks ‘rejuvenated’ the leg blood flow responses of the older people. They became identical to those in the young,” said Professor Rennie.

“I am extremely pleased with progress,” he said. “Our team is making good headway in finding more and more out about what causes the loss of muscle with age. It looks like we have good clues about how to lessen it with weight training and

Study Information

1.Emilie A Wilkes, Anna L Selby, Philip J Atherton, Rekha Patel, Debbie Rankin, Ken Smith, and Michael J Rennie.
Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia.
American Journal of Clinical Nutrition
2009 September
University of Nottingham, School of Graduate Entry Medicine and Health, Derby, United Kingdom