The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults.

Populations encompassing extremes of age, including neonates and elderly, have greater mortality from sepsis. We propose that the increased mortality observed in the neonatal and elderly populations after sepsis is due to fundamental differences in host protective immunity, and are manifested at the level of the leukocyte transcriptome. Neonatal (5–7 days), young adult (6–12 weeks), or elderly (20–24 months) mice underwent a cecal slurry model of intra-abdominal sepsis. Both neonatal and elderly mice exhibited significantly greater mortality to sepsis (p<0.05). Neonates in particular exhibited significant attenuation of their inflammatory response (p<0.05), as well as reductions in cell recruitment and reactive oxygen species production (both p<0.05), all of which could be confirmed at the level of the leukocyte transcriptome. In contrast elderly mice were also more susceptible to abdominal peritonitis, but this was associated with no significant differences in the magnitude of the inflammatory response, reduced bacterial killing (p<0.05), reduced early myeloid cell activation (p<0.05) and a persistent inflammatory response that failed to resolve. Interestingly, elderly mice expressed a persistent inflammatory and immunosuppressive response at the level of the leukocyte transcriptome, with failure to return to baseline by three days. This study reveals that neonatal and elderly mice have profoundly different responses to sepsis that are manifested at the level of their circulating leukocyte transcriptome, although the net result of increased mortality, is similar. Considering these differences are fundamental aspects of the genomic response to sepsis, interventional therapies will require individualization based on the age of the population.

Objective Post-traumatic knee osteoarthritis is prevalent after anterior cruciate ligament reconstruction. Biomarkers that identify individuals likely to develop osteoarthritis, especially symptomatic osteoarthritis, can help target preventative and therapeutic strategies. This study examined the magnitude and change over time in urinary CTX-II (uCTX-II) concentrations shortly after ACL reconstruction, and, secondarily, the associations with knee pain and function. Design Subjects were 28 patients with ACL reconstruction (ACLR) and 28 age- and sex-matched controls (CNTRL). Testing was conducted at 4 time points spaced 4 weeks apart (4, 8, 12 and 16 weeks post-operative in ACLR). Measures included demographics, urine samples, Numeric Pain Rating Scale (NPRS) and International Knee Documentation Committee Subjective Knee Form (IKDC-SKF). uCTX-II concentrations were determined with competitive ELISA. uCTX-II concentrations at each time point in ACLR were compared to the mean concentration over time in CNTRL, with and without adjustment for body mass index (BMI). Changes over time in each measure and correlations between the slopes of change were examined. Results uCTX-II concentrations were significantly higher in ACLR than CNTRL through 16 weeks post-operative when adjusted for BMI. In ACLR, uCTX-II concentrations significantly decreased over time, and the slope was associated with NPRS (r =.406, p=.039) and IKDC-SKF (r = −.402, p = .034) slopes. Conclusion uCTX-II concentrations shortly after ACL reconstruction were elevated compared to controls and declined over time. Decreasing uCTX-II concentrations were associated with decreasing knee pain and improving function. uCTX-II may have a role as a prognostic marker following ACL reconstruction and warrants further investigation.