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Background: Growth and differentiation factors 8 (GDF8) and 11 (GDF11) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be affected by circulating antagonists such as their respective prodomains, follistatin (FST315), WFIKKN1, and WFIKKN2. Reports of the relationship of GDF8 and GDF11 and their antagonists with aging and aging phenotypes such as skeletal muscle strength have been conflicting possibly because of difficulties in measuring these proteins and polypeptides.Methods: Plasma GDF8 and GDF11 and their antagonists were measured using a multiplexed selected reaction monitoring assay and liquid chromatography-tandem mass spectrometry in 160 healthy adults aged 22-93 years. Quadriceps strength was measured by knee extensor torque using isokinetic dynamometry.Results: Spearman correlations with age were the following: GDF11 prodomain (r = .30, p = .001), GDF11 mature protein (r = .23, p = .004), FST315 (r = .32, p < .0001), WFIKKN1 (r = -.21, p = 0.008), and WFIKKN2 (r = .18, p = .02). Independent of age, FST315 and WFIKKN1 were negatively associated with knee strength (p = .02, p = .03, respectively) in a multivariable model that included both GDF8 and GDF11 mature proteins.Conclusions: When measured by an antibody-free selected reaction monitoring assay, GDF8, GDF11, and their antagonists are found in the circulation in the ng/mL range. In healthy adults, plasma GDF11 and antagonists FST315, WFIKKN1, and WFIKKN2 differed by age. Antagonists of GDF8 and GDF11, but not GDF8 and GDF11, were independently associated with skeletal muscle strength. Further work is needed to characterize the relationship of these protein and polypeptides with sarcopenia-related phenotypes such as physical function and walking disability. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation has been linked to memory and other cognitive impairments, as well as Alzheimer's disease. Here, we investigate the association between inflammatory markers and changes in brain activity measured by regional cerebral blood flow (rCBF) to assess the relationship between inflammation and brain function in older individuals.Methods: Annual 15O water resting-state positron emission tomography (PET) scans collected over a 5-year period were assessed in 138 cognitively normal older participants (77 males; mean age at baseline = 71.3; mean scans per participant = 3.5) in the Baltimore Longitudinal Study of Aging. Voxel-wise linear mixed models were used to investigate associations between rCBF and C-reactive protein (CRP) and interleukin-6 (IL-6) at the time of scanning. We examined relationships between baseline CRP and IL-6 levels and baseline rCBF, and relationships between baseline and mean inflammatory levels over time and longitudinal rCBF changes.Results: Higher baseline CRP and IL-6 were each associated with lower baseline rCBF primarily in frontal and occipital regions, with only the lingual gyrus surviving atrophy correction. Higher baseline and mean CRP were also associated with greater rCBF declines over time in anterior cingulate and hippocampal regions, whereas higher baseline and mean IL-6 levels were associated with greater rCBF declines in orbitofrontal and hippocampal regions.Conclusions: Higher levels of inflammation are associated with longitudinal changes in brain function in regions important for cognition. These results, along with previous studies, suggest that chronic inflammation in older adults may contribute to age-associated declines in cognitive function. [ABSTRACT FROM AUTHOR]

Background: Age-related changes in testosterone levels in older persons and especially in women have not been fully explored. The objective of this study was to describe age-related trajectories of total testosterone (TT), ammonium sulfate precipitation-measured bioavailable testosterone (mBT), and sex hormone-binding glycoprotein (SHBG) in men and women from the Baltimore Longitudinal Study of Aging, with special focus on the oldest adults.Methods: Participants included 788 White men and women aged 30-96 years with excellent representation of old and oldest old, who reported not taking medications known to interfere with testosterone. Longitudinal data were included when available. TT, mBT, and SHBG were assayed. Age-related trajectories of mBT were compared with those obtained using calculated bioavailable testosterone (cBT). Generalized least square models were performed to describe age-related trajectories of TT, mBT, and SHBG in men and women.Results: mBT linearly declines over the life span and even at older ages in both sexes. In men, TT remains quite stable until the age of 70 years and then declines at older ages, whereas in women TT progressively declines in premenopausal years and slightly increases at older ages. Differences in age-related trajectories between total and bioavailable testosterone are only partially explained by age changes in SHBG, whose levels increases at accelerated rates in old persons. Noteworthy, although mBT and cBT highly correlated with one another, mBT is a much stronger correlate of chronological age than cBT.Conclusion: In both men and women, mBT linearly declines over the life span and even at old ages. Its relationship with age-related phenotypes should be further investigated. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that mildly down-regulated thyroid function in older persons may protect and/or reflect maintained health.Methods: Using observational data collected between January 2006 and March 2014 on a volunteer sample of 602 men and women aged 68-97 years with normal thyroid function participating in the Baltimore Longitudinal Study of Aging, this study examines the concurrent relationship between reported walking ability, usual and rapid gait speed, endurance walk performance, fatigability, and reported energy level with respect to free thyroxine (FT4) within the normal range (0.76-1.50ng/dL) as a continuous variable and categorized as low (lower quartile), medium (interquartile), or high (upper quartile).Results: Adjusting for sex, age, race, height, weight, exercise and smoking, reported walking ability, usual and rapid gait speed, 400-m time, fatigability, and reported energy level were less favorable with increasing FT4 (p = .013 to <.001). In sex-strata, similar associations were observed except for walking ability in men and energy level in women. Categorical analyses revealed that persons with low FT4 exhibited better functional mobility, fitness, and reported energy than persons with intermediate or high levels (p < .05 for all). Persons with high-normal versus medium FT4 had slower usual and rapid gait speed (p < .05) only.Conclusion: Older adults with low-normal FT4 exhibit better mobility, fitness, and fatigue profiles. Mildly down-regulated thyroid function appears to align with better function in old age and may serve as a biomarker of healthy longevity. [ABSTRACT FROM AUTHOR]

Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact. [ABSTRACT FROM PUBLISHER]

Focuses on the effect of glucagon-like peptide-1 on insulin-mediated glucose disposal in elderly patients with type 2 diabetes. Values of plasma glucose, insulin and C-peptide levels during the euglycemic clamp studies; Results of the plasma glucagon and total and active glucose-like peptide-1 levels during the euglycemic clamp studies; Measurement of glucose production and disposal rates using tritiated glucose methodology.

Background: The current studies were designed to examine the effect of aging and diabetes on the enteroinsular axis.Methods: Healthy young control subjects (n = 10 young; age 23 +/- 1 years; body mass index [BMI] 24 +/- 1 kg/m(2)), healthy elderly subjects (n = 10; age 80 +/- 2 years; BMI 26 +/- 1 kg/m(2)), and elderly patients with type 2 diabetes (n = 10; age 76 +/- 2 years; BMI 26 +/- 2 kg/m(2)) underwent a 3-hour oral glucose tolerance test (glucose dose 40 gm/m(2)).Results: Insulin responses were not different between young controls and elderly patients with diabetes but were significantly lower in elderly patients with diabetes and young controls than in elderly controls (young control: 178 +/- 27 pM; elderly control: 355 +/- 57 pM; elderly diabetes: 177 +/- 30 pM; p <.05 elderly control vs young control and elderly diabetes). Total glucagon-like peptide 1 (GLP-1) responses were not significantly different between young and elderly controls and patients with diabetes (young control: 15 +/- 2 pM; old control: 8 +/- 2 pM; elderly diabetes: 12 +/- 3 pM; p = ns). Active GLP-1 responses were also not different between young and elderly controls and patients with diabetes (young control: 5 +/- 1 pM; old control: 6 +/- 1 pM; elderly diabetes: 7 +/- 1 pM; p = ns). However, the difference between total and active GLP levels was significantly greater in the young controls (young control: 10 +/- 2 pM; old control: 2 +/- 2 pM; elderly diabetes: 4 +/- 2 pM; p <.05, young vs elderly). Glucose-dependent insulinotropic polypeptide responses were not different between young and elderly controls and between elderly controls and patients with diabetes but were significantly higher in elderly patients with diabetes than in young controls (young control: 97 +/- 12 pM; elderly control: 121 +/- 16 pM; elderly diabetes: 173 +/- 27 pM; p <.05, young vs elderly diabetes). Glucagon responses were reduced in elderly controls but were similar in young controls and elderly patients with diabetes (young control: 15 +/- 1 pM; elderly control: 9 +/- 1 pM; elderly diabetes: 16 +/- 1 pM; p <.01 elderly control vs young control and elderly diabetes). Dipeptidyl peptidase IV levels were lower in both elderly controls and patients with diabetes when compared with young controls (young control: 0.17 +/- 0.01; elderly control: 0.15 +/- 0.01; elderly diabetes: 0.15 +/- 0.01 DeltaOD/20 minutes; p <.05, elderly vs young).Conclusions: We conclude that normal aging and diabetes are associated with multiple changes in the enteroinsular axis. [ABSTRACT FROM AUTHOR]