The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (M(r)) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-1 beta-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.

Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target.

Objective To validate the FRAIL scale. Design Longitudinal study. Setting Community. Participants Representative sample of African Americans age 49 to 65 years at onset of study. Measurements The 5-item FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight), at baseline and activities of daily living (ADLs), instrumental activities of daily living (IADLs), mortality, short physical performance battery (SPPB), gait speed, one-leg stand, grip strength and injurious falls at baseline and 9 years. Blood tests for CRP, SIL6R, STNFR1, STNFR2 and 25 (OH) vitamin D at baseline. Results Cross-sectionally the FRAIL scale correlated significantly with IADL difficulties, SPPB, grip strength and one-leg stand among participants with no baseline ADL difficulties (N=703) and those outcomes plus gait speed in those with no baseline ADL dependencies (N=883). TNFR1 was increased in pre-frail and frail subjects and CRP in some subgroups. Longitudinally (N=423 with no baseline ADL difficulties or N=528 with no baseline ADL dependencies), and adjusted for the baseline value for each outcome, being pre-frail at baseline significantly predicted future ADL difficulties, worse one-leg stand scores, and mortality in both groups, plus IADL difficulties in the dependence-excluded group. Being frail at baseline significantly predicted future ADL difficulties, IADL difficulties, and mortality in both groups, plus worse SPPB in the dependence-excluded group. Conclusion This study has validated the FRAIL scale in a late middle-aged African American population. This simple 5-question scale is an excellent screening test for clinicians to identify frail persons at risk of developing disability as well as decline in health functioning and mortality.

BackgroundA brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients. To screen for persons with sarcopenia, we developed a simple five‐item questionnaire (SARC‐F) based on cardinal features or consequences of sarcopenia.MethodsWe investigated the utility of SARC‐F in the African American Health (AAH) study, Baltimore Longitudinal Study of Aging (BLSA), and National Health and Nutrition Examination Survey (NHANES). Internal consistency reliability for SARC‐F was determined using Cronbach's alpha. We evaluated SARC‐F factorial validity using principal components analysis and criterion validity by examining its association with exam‐based indicators of sarcopenia. Construct validity was examined using cross‐sectional and longitudinal differences among those with high (≥4) vs. low (<4) SARC‐F scores for mortality and health outcomes.ResultsSARC‐F exhibited good internal consistency reliability and factorial, criterion, and construct validity. AAH participants with SARC‐F scores ≥ 4 had more Instrumental Activity of Daily Living (IADL) deficits, slower chair stand times, lower grip strength, lower short physical performance battery scores, and a higher likelihood of recent hospitalization and of having a gait speed of <0.8 m/s. SARC‐F scores ≥ 4 in AAH also were associated with 6 year IADL deficits, slower chair stand times, lower short physical performance battery scores, having a gait speed of <0.8 m/s, being hospitalized recently, and mortality. SARC‐F scores ≥ 4 in the BLSA cohort were associated with having more IADL deficits and lower grip strength (both hands) in cross‐sectional comparisons and with IADL deficits, lower grip strength (both hands), and mortality at follow‐up. NHANES participants with SARC‐F scores ≥ 4 had slower 20 ft walk times, had lower peak force knee extensor strength, and were more likely to have been hospitalized recently in cross‐sectional analyses.ConclusionsThe SARC‐F proved internally consistent and valid for detecting persons at risk for adverse outcomes from sarcopenia in AAH, BLSA, and NHANES.