New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up ...for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance- and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, ≥1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults who have acute or chronic diseases need even more dietary protein (ie, 1.2–1.5 g/kg body weight/d). Older people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73m2), but who are not on dialysis, are an exception to this rule; these individuals may need to limit protein intake. Protein quality, timing of ingestion, and intake of other nutritional supplements may be relevant, but evidence is not yet sufficient to support specific recommendations. Older people are vulnerable to losses in physical function capacity, and such losses predict loss of independence, falls, and even mortality. Thus, future studies aimed at pinpointing optimal protein intake in specific populations of older people need to include measures of physical function.
Leucine supplementation has grown in popularity due to the discovery of its anabolic effects on cell signaling and protein synthesis in muscle. The current recommendation is a minimum intake of 55 mg ...⋅ kg
d
Leucine acutely stimulates skeletal muscle anabolism and can overcome the anabolic resistance of aging. The value of chronic leucine ingestion for muscle growth is still unclear. Most of the research into leucine consumption has focused on efficacy. To our knowledge, very few studies have sought to determine the maximum safe level of intake. Limited evidence suggests that intakes of ≤1250 mg ⋅ kg
d
do not appear to have any health consequences other than short-term elevated plasma ammonia concentrations. Similarly, no adverse events have been reported for the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), although no studies have tested HMB toxicity in humans. Therefore, future research is needed to evaluate leucine and HMB toxicity in the elderly and in specific health conditions.
Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in ...glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.
Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains ...unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans.
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•BAT activation is associated with accelerated lipid metabolism•Cold induced the expression of genes involved in lipid metabolism in BAT•BAT mitochondrial thermogenesis is 45-fold greater than that of WAT•Cold leads to a delayed decrease in TG and VLDL levels
Chondronikola et al. explore the role of BAT in lipid metabolism in humans and show that cold-induced BAT activation is associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Cold upregulates the expression of genes involved in lipid metabolism specifically in BAT.
Key points
Five days of bed rest resulted in a reduction in leg lean mass and strength in older adults.
After bed rest, older (but not younger) adults had reduced amino acid‐induced anabolic ...sensitivity (blunted muscle protein synthesis; MPS) and enhanced markers associated with the ubiquitin proteasome and autophagy–lysosomal systems (increase in molecular markers related to muscle proteolysis).
Younger adults did not lose leg lean mass (via DXA) after 5 days of bed rest despite blunted amino acid‐induced mTORC1 signalling and increased skeletal muscle REDD1, REDD2 and MURF1 mRNA expression.
Exercise rehabilitation restored bed rest‐induced deficits in lean mass, strength, nutrient‐induced protein anabolism (protein synthesis and mTORC1 signalling) and select muscle proteolytic markers in older adults.
Bed rest‐induced muscle loss and impaired muscle recovery may contribute to age‐related sarcopenia. It is unknown if there are age‐related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5‐day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual‐energy X‐ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA‐induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA‐induced protein synthesis rates and increased MAFBX mRNA, p‐AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short‐term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest‐induced deficits in lean mass and strength in older adults.
Role of dietary protein in the sarcopenia of aging Paddon-Jones, Douglas; Short, Kevin R; Campbell, Wayne W ...
The American journal of clinical nutrition,
05/2008, Letnik:
87, Številka:
5
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Sarcopenia is a complex, multifactorial process facilitated by a combination of factors including the adoption of a more sedentary lifestyle and a less than optimal diet. Increasing evidence points ...to a blunted anabolic response after a mixed nutrient meal as a likely explanation for chronic age-related muscle loss. There is currently insufficient longer-term research with defined health outcomes to specify an optimal value for protein ingestion in elderly individuals. However, there is general agreement that moderately increasing daily protein intake beyond 0.8 g·kg⁻¹·d⁻¹ may enhance muscle protein anabolism and provide a means of reducing the progressive loss of muscle mass with age. The beneficial effects of resistance exercise in aging populations are unequivocal. However, research has not identified a synergistic effect of protein supplementation and resistance exercise in aging populations. There is little evidence that links high protein intakes to increased risk for impaired kidney function in healthy individuals. However, renal function decreases with age, and high protein intake is contraindicated in individuals with renal disease. Assessment of renal function is recommended for older individuals before they adopt a higher-protein diet.
The loss of skeletal muscle size and function with aging and sarcopenia may be related, in part, to an age-related muscle protein synthesis impairment. In this review, we discuss to what extent aging ...affects skeletal muscle protein synthesis and how nutrition and exercise can be used strategically to overcome age-related protein synthesis impairments and slow the progression of sarcopenia.
Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known ...about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of ‘DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)’. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted ‘skin aging–associated secreted proteins (SAASP)’. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of ‘metabolism’ and ‘adherens junction interactions’ was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging.
The loss of skeletal muscle mass during aging, sarcopenia, increases the risk for falls and dependence. Resistance exercise (RE) is an effective rehabilitation technique that can improve muscle mass ...and strength; however, older individuals are resistant to the stimulation of muscle protein synthesis (MPS) with traditional high-intensity RE. Recently, a novel rehabilitation exercise method, low-intensity RE, combined with blood flow restriction (BFR), has been shown to stimulate mammalian target of rapamycin complex 1 (mTORC1) signaling and MPS in young men. We hypothesized that low-intensity RE with BFR would be able to activate mTORC1 signaling and stimulate MPS in older men. We measured MPS and mTORC1-associated signaling proteins in seven older men (age 70+/-2 yr) before and after exercise. Subjects were studied identically on two occasions: during BFR exercise bilateral leg extension exercise at 20% of 1-repetition maximum (1-RM) with pressure cuff placed proximally on both thighs and inflated at 200 mmHg and during exercise without the pressure cuff (Ctrl). MPS and phosphorylation of signaling proteins were determined on successive muscle biopsies by stable isotopic techniques and immunoblotting, respectively. MPS increased 56% from baseline after BFR exercise (P<0.05), while no change was observed in the Ctrl group (P>0.05). Downstream of mTORC1, ribosomal S6 kinase 1 (S6K1) phosphorylation and ribosomal protein S6 (rpS6) phosphorylation increased only in the BFR group after exercise (P<0.05). We conclude that low-intensity RE in combination with BFR enhances mTORC1 signaling and MPS in older men. BFR exercise is a novel intervention that may enhance muscle rehabilitation to counteract sarcopenia.
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