The list of all compounds tested by

The list of all compounds tested by the ITP and in progress is on the ITP website at . To date, six compounds have shown significant extension of lifespan: The positive findings illustrate some important aspects for aging interventions research. The effective interventions appear to include several disparate mechanisms, demonstrating that many cellular pathways might be exploited to influence lifespan and aging. Rapamycin modulates the nutrient-sensing pathways via its interaction with mTOR (). Acarbose was anticipated to work as a caloric restriction mimetic due to its ability to reduce the rate of jnk pathway of carbohydrates, but its mechanism of action appears more complex, since caloric restriction results in significant lifespan extension in both male and female UM-HET3 mice (), while the effects of acarbose were much larger in males (). Aspirin is known for its anti-inflammatory and antioxidant activities, NDGA also has anti-inflammatory and antioxidant activities, 17αEstradiol has neuro-protective properties independent of binding to the estrogen receptor, and Protandim® activates Nrf2 transcriptional regulator (). This diverse group of interventions demonstrates the complex nature of the biology of aging. Another major surprise is the extent of sex differences in response to the interventions. Four of the six positive interventions only worked in one sex, and the two that had an effect in both sexes showed sex-specific differences in the extent of the effect. Blood levels of a compound sometimes differed between males and females, but that did not always explain the sex difference in lifespan extension. For rapamycin, achieving approximately equivalent blood levels in males and females by treating with different doses did result in similar increases in lifespan (). But for NDGA, even at doses giving similar blood levels in males and females, females still did not respond (). The ITP\'s findings illustrate how important it is to examine the effects of interventions in both sexes and suggest that further studies on the mechanism of these sex effects may yield important insights into the underlying biology, and guidance for eventually clinical studies.
Frailty is a geriatric syndrome encompassing a range of biological and behavioral changes hat impact our longevity and quality of life, and also highlight a person\'s vulnerability across multiple forms of stress. In this commentary, we review consequences of the frailty syndrome regarding changes in postural control from two perspectives: First, the physical changes due to declines in a range of physiological systems which lead to an increased incidence of falls in the elderly; second, the functional or ‘embodied’ role of posture as a facilitator of goal oriented activity. The former reviews postural changes as a function of the physiological and biomechanical status of the aging individual, while the latter focuses on changes in the postural system as a facilitator of successful task engagement.
Introduction Senescent cells accumulate with age in a wide range of tissues. Frequencies in excess of 5%, and sometimes as much as 20% and more, have been reported in tissues from old animals both with high (white blood cells (Akbar et al., 2016); crypt enterocytes (Jurk et al., 2014; Wang et al., 2009)) and low (dermal fibroblasts (Dimri et al., 1995), hepatocytes (Jurk et al., 2014; Wang et al., 2009), fat progenitors (Schafer et al., 2016), osteocytes (Farr et al., 2016)) proliferation rates as well as in postmitotic tissues (neurons (Jurk et al., 2012)). The rate of accumulation of senescent cells in liver and intestinal crypts predicts median and maximum lifespan of mice in cohorts with widely different aging rates (e.g. late generation vs wt and dietary restricted C57Bl/6) (Jurk et al., 2014). More importantly, interventions that selectively ablate senescent cells by genetic and/or pharmacologic means may improve healthspan and lifespan in mice (Baker et al., 2016; Demaria et al., 2017; Xu et al., 2015).