Identification and Application of Gene Expression Signatures Associated with Lifespan Extension.

Tyshkovskiy A, Bozaykut P, Borodinova AA, Gerashchenko MV, Ables GP, Garratt M, Khaitovich P, Clish CB, Miller RA, Gladyshev VN.

Cell Metab. 2019 Sep 3;30(3):573-593.e8. doi: 10.1016/j

PMID: 31353263 

Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.

https://www.ncbi.nlm.nih.gov/pubmed/31353263

OFAS Successfully Hosted AGA Session

OFAS Successfully Hosted AGA Session

This year, OFAS hosted a pre-meeting session at the AGE 47th Annual Meeting in Philadelphia. The theme of the conference was “Improving Resiliency to Delay Aging”, and the OFAS-sponsored session was focused on Nutrition and Longevity. The panel of speakers included: Dr. Sebastian Brandhorst from University of Southern California; Dr. John Newman from the Buck Institute and UCSF; Dr. John P. Richie from Penn State University; and Dr. Brian Kennedy from the Yong Loo Lin School of Medicine at the National University of Singapore. There were 261 attendees present at the meeting, including some directors for the Nathan Shock Centers and NIH-NIA.

For years, Orentreich Foundation for the Advancement of Science has researched biomedical interventions to prevent, halt, or reverse those disorders that decrease the quality or length of life. Our groundbreaking research on dietary methionine restriction has shown its dramatic ability to increase longevity while improving healthspan, lowering body weight, and reducing the incidence of age-related diseases.

In addition to our dedication to discovery, we are also committed to promoting the exchange of knowledge and strengthening of relationships within the scientific community. We host a biennial symposium on healthy aging, support meetings in the field, and, each year, our scientists represent us at conferences and seminars around the globe.

 

OFAS Hosting Session at AGE 47th Annual Meeting

OFAS Hosting Session at AGE 47th Annual Meeting

For years, Orentreich Foundation for the Advancement of Science has researched biomedical interventions to prevent, halt, or reverse those disorders that decrease the quality or length of life. Our groundbreaking research on dietary methionine restriction has shown its dramatic ability to increase longevity while improving healthspan, lowering body weight, and reducing the incidence of age-related diseases.

In addition to our dedication to discovery, we are also committed to promoting the exchange of knowledge and strengthening of relationships within the scientific community. We host a biennial symposium on healthy aging, support meetings in the field, and, each year, our scientists represent us at conferences and seminars around the globe.

This year, OFAS will host a pre-meeting session at the AGE 47th Annual Meeting in Philadelphia. The theme of the conference is “Improving Resiliency to Delay Aging”, and the OFAS-sponsored session is focused on Nutrition and Longevity. The panel of speakers includes: Dr. Sebastian Brandhorst from University of Southern California; Dr. John Newman from the Buck Institute and UCSF; Dr. John P. Richie from Penn State University; and Dr. Brian Kennedy from the Yong Loo Lin School of Medicine at the National University of Singapore.

High Fat Diet Extends Longevity and Healthspan

High Fat Diet Extends Longevity and Healthspan

KD longevity graph

As more people age well past their 70s, researchers have increasingly explored the issues of health and quality of life during aging. A recent mouse study at the UC Davis School of Veterinary Medicine sheds revealed that a high-fat, or ketogenic, diet not only increases longevity, but improves physical strength as well.

Ketogenic diets have gained popularity for a variety of health benefit claims, but scientists are still teasing out what happens during ketosis, when carbohydrate intake is so low that the body shifts from using glucose as the main fuel source to burning fat and producing ketones for energy.

While calorie restriction has been shown to slow aging in many animals, Roberts et. al. were interested in how a high-fat diet may impact the aging process. In their research, they found  a 13% increase in median life span for the mice on a high-fat versus high-carb diet.

The study mice were split into three groups: a regular rodent high-carb diet, a low-carb/high-fat diet, and a ketogenic diet (89-90 percent of total calorie intake). Originally concerned that the high-fat diet would increase weight and decrease lifespan, the researchers kept the calorie count of each diet the same.

In addition to significantly increasing the median lifespan of mice in the study, the ketogenic diet increased memory and motor function, prevented an increase in age-related markers of inflammation, and reduced the incidence of tumors. This indicates that a ketogenic diet can have a major impact on life- and health span without major weight loss or restriction of food intake. It also opens a new avenue for possible dietary interventions that have an impact on aging.

Future studies are warranted to investigate the mechanisms through which this diet works and to optimize diet composition and feeding approaches to further extend healthspan.