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jtitle_s:("Age (dodr)")
1.  Decreased insulin sensitivity and increased oxidative damage in wasting adipose tissue depots of wild-type mice 
Age  2011;34(5):1225-1237.
Unintentional weight loss (wasting) in the elderly is a major health concern as it leads to increased mortality. Several studies have focused on muscle loss, but little is known about the mechanisms giving rise to loss of fat mass at old ages. To investigate potential mechanisms, white adipose tissue (WAT) characteristics and proteomic profiles were compared between adult (10–12-month-old) and aged (22–24-month-old) wild-type mice. Four individual WAT depots were analyzed to account for possible depot-specific differences. Proteomic profiles of WAT depots, along with body weights and compositions, plasma levels of insulin, leptin and adiponectin, insulin tolerance, adipocyte sizes, and products of oxidative damage in each WAT depot were determined. We found that lean mass remained constant while fat mass and insulin tolerance were decreased in old age, as were adipocyte sizes in the WAT depots. Proteomic results showed increased levels of enolase, pyruvate dehydrogenase E1β, NAD+−dependent isocitrate dehydrogenase α, and ATP synthase subunit β, and decreased levels of carbonic anhydrase 3 in WAT of aged mice. These data suggest increased aerobic glucose oxidation in wasting WAT, consistent with decreased insulin signaling. Also, Cu/Zn superoxide dismutase and two chaperones were increased in aged WAT depots, indicating higher stress resistance. In agreement, lipid peroxidation (HNE-His adducts) increased in old age, although protein oxidation (carbonyl groups) showed no increase. In conclusion, features of wasting WAT were similar in the four depots, including decreased adipocyte sizes and alterations in protein expression profiles that indicated decreased insulin sensitivity and increased lipid peroxidation.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-011-9304-7) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-011-9304-7
PMCID: PMC3448990  PMID: 21953241
Wasting; Aging; White adipose tissue depots; Proteomics; Oxidative damage; Stress resistance; Insulin resistance
3.  Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats 
Age  2010;33(2):167-183.
The primary purpose of the present set of studies was to provide a direct comparison of the effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin receptor blocker losartan on body composition, physical performance, and muscle quality when administered late in life to aged rats. Overall, enalapril treatment consistently attenuated age-related increases in adiposity relative to both placebo and losartan. The maximal effect was achieved after 3 months of treatment (between 24 and 27 months of age), at a dose of 40 mg/kg and was observed in the absence of any changes in physical activity, body temperature, or food intake. In addition, the reduction in fat mass was not due to changes in pathology given that enalapril attenuated age-related increases in tumor development relative to placebo- and losartan-treated animals. Both enalapril and losartan attenuated age-related decreases in grip strength, suggesting that changes in body composition appear dissociated from improvements in physical function and may reflect a differential impact of enalapril and losartan on muscle quality. To link changes in adiposity to improvements in skeletal muscle quality, we performed gene array analyses to generate hypotheses regarding cell signaling pathways altered with enalapril treatment. Based on these results, our primary follow-up pathway was mitochondria-mediated apoptosis of myocytes. Relative to losartan- and placebo-treated rats, only enalapril decreased DNA fragmentation and caspase-dependent apoptotic signaling. These data suggest that attenuation of the severity of skeletal muscle apoptosis promoted by enalapril may represent a distinct mechanism through which this compound improves muscle strength/quality.
doi:10.1007/s11357-010-9196-y
PMCID: PMC3127467  PMID: 21153712
Age-related adiposity; Body composition; Sarcopenia; Renin–angiotensin system; Physical function; Muscle quality
4.  Do long-lived mutant and calorie-restricted mice share common anti-aging mechanisms?—a pathological point of view 
Age  2006;28(2):163-171.
Rodent models are an invaluable resource for studying the mechanism of mammalian aging. In recent years, the availability of transgenic and knockout mouse models has facilitated the study of potential mechanisms of aging. Since 1996, aging studies with several long-lived mutant mice have been conducted. Studies with the long-lived mutant mice, Ames and Snell dwarf, and growth hormone receptor/binding protein knockout mice, are currently providing important clues regarding the role of the growth hormone/insulin like growth factor-1 axis in the aging process. Interestingly, these studies demonstrate that these long-lived mutant mice have physiological characteristics that are similar to the effects of calorie restriction, which has been the most effective experimental manipulation capable of extending lifespan in various species. However, a question remains to be answered: do these long-lived mutant and calorie-restricted mice extend their lifespan through a common underlying mechanism?
doi:10.1007/s11357-006-9007-7
PMCID: PMC2464730  PMID: 19943137
aging; growth hormone receptor/binding protein; knockout mouse; neoplastic disease

Results 1-4 (4)