Associations between Differential Aging and Lifestyle, Environment, Current, and Future Health Conditions: Findings from Canadian Longitudinal Study on Aging.

INTRODUCTION: An aging population will bring a pressing challenge for the healthcare system. Insights into promoting healthy longevity can be gained by quantifying the biological aging process and understanding the roles of modifiable lifestyle and environmental factors, and chronic disease conditions. METHODS: We developed a biological age (BioAge) index by applying multiple state-of-art machine learning models based on easily accessible blood test data from the Canadian Longitudinal Study of Aging (CLSA). The BioAge gap, which is the difference between BioAge index and chronological age, was used to quantify the differential aging, i.e., the difference between biological and chronological age, of the CLSA participants. We further investigated the associations between the BioAge gap and lifestyle, environmental factors, and current and future health conditions. RESULTS: BioAge gap had strong associations with existing adverse health conditions (e.g., cancers, cardiovascular diseases, diabetes, and kidney diseases) and future disease onset (e.g., Parkinson's disease, diabetes, and kidney diseases). We identified that frequent consumption of processed meat, pork, beef, and chicken, poor outcomes in nutritional risk screening, cigarette smoking, exposure to passive smoking are associated with positive BioAge gap ("older" BioAge than expected). We also identified several modifiable factors, including eating fruits, legumes, vegetables, related to negative BioAge gap ("younger" BioAge than expected). CONCLUSIONS: Our study shows that a BioAge index based on easily accessible blood tests has the potential to quantify the differential biological aging process that can be associated with current and future adverse health events. The identified risk and protective factors for differential aging indicated by BioAge gap are informative for future research and guidelines to promote healthy longevity.

Multiple hepatic arterial injections of recombinant adenovirus p53 and 5-fluorouracil after transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a pilot phase II trial.

This pilot phase II study was designed to determine the efficacy, toxicities, and biological activity of multiple hepatic arterial injections of recombinant adenovirus p53 (rAd-p53) and 5-fluorouracil (5-FU) after transcatheter arterial chemoembolization (TACE) when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC). Forty-six patients with unresectable HCC were randomized in either group 1 [23 patients, multiple hepatic arterial injections of Ad-p53 (1x10 viral particles) and 5-FU (500-750 mg), after TACE] or group 2 (23 patients, TACE alone). In group 1, the number of Ad-p53/5-FU courses administered was 166 (median 7, range 3-12). In group 2, the number of TACE courses administered was 47 (median 2, range 1-3). Partial response and stable disease were 69.5% in group 1 and 65.2% in group 2. Times to progression were 9.6 months (range 2.1-21.7) in group 1 and 8.3 months (range 2.1-16.8) in group 2. Overall survivals were 12.8 months (range 2.7-26.2) in group 1 and 10.4 months (range 2.7-22.5) in group 2. Toxicities in both groups were generally mild and reversible. The most common Ad-p53-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues. Distribution studies revealed that the vector was detected in the plasma, but rarely in the gargle and urine. This study shows that multiple hepatic arterial injections of Ad-p53 and 5-FU after TACE can be active and safe as a treatment for patients with unresectable HCC.