Location: Jean Mayer Human Nutrition Research Center On Aging
2025 Annual Report
Objectives
Objective 1: Define the impact of dietary patterns, specific foods and food components, and physical activity on healthy aging and mitigation of age-related chronic diseases.
Subobjective 1.A: Relate bone microarchitecture, chronic disease, and change in bone mineral density in older adults.
Subobjective 1.B: Determine the impact of protein and alkali supplementation on skeletal muscle performance and physical function.
Subobjective 1.C: Assess the effect of vitamin K supplementation on lower-extremity function in adults with osteoarthritis.
Objective 2: Elucidate the mechanisms of action and identify the physiologic processes by which dietary patterns, specific foods and food components, and physical activity promote healthy aging and mitigate age-related chronic diseases.
Subobjective 2.A: Determine the impact of dietary patterns, foods and food components on the gut microbiome, metabolome, transcriptome and biological pathways associated with chronic disease factors.
Subobjective 2.B. Determine the in vitro effect of chitin (primary component of the cricket exoskeleton) metabolites on the cancer-permissive milieu produced by obesity in mouse and human colonic organoids.
Subobjective 2.C. Investigate the effect of zinc supplementation on immune responsiveness in older adults.
Subobjective 2.D: Investigate the physiological and behavioral systems that contribute to variability in weight change following weight loss in adults with obesity.
Objective 3: Identify, develop and evaluate assessment tools, biomarkers and surrogate markers of diet quality and physical activity that reflect healthy aging.
Subobjective 3.A: Assess the feasibility of using wearable inertial sensors to assess gait parameters in nutrition interventions.
Subobjective 3.B: Develop a dietary self-monitoring app and evaluate its effect on participant engagement and weight loss.
Approach
The prevalence of age-related chronic diseases, such as musculoskeletal, cardiometabolic, and cancer increases with advancing years and is associated with increased morbidity and mortality risk, loss of independence, diminished quality of life and elevated health care costs. Our approach to improve this situation is to address issues that will delay the onset and decrease the progression of age-related chronic diseases, with the aim of increasing healthspan (period in the lifecycle of good health) among diverse populations. By integrating clinical, basic, and pragmatic research, the proposed projects will contribute to the evidence base on which strategies to prevent and treat age-related chronic diseases are based.
We will achieve our aim by addressing three main areas. (1) Define the impact of type 2 diabetes and vitamin B6 status on bone mass and architectural integrity; determine the effect of alkaline salt supplementation on reducing the negative impact of dietary protein acid load on muscle mass; and assess the effects of vitamin K supplementation on lower-extremity function. (2) Determine the interplay between dietary fat and gut microbiota composition, diversity, and derived metabolites on cardiometabolic risk factors and biomarkers thereof; determine the in vitro effect of chitin (primary component of the cricket exoskeleton) metabolites on the cancer-permissive milieu produced by obesity; evaluate the impact of zinc supplementation on immune-responsiveness; and identify determinants of behavioral systems that contribute to variability in weight change following weight loss. (3) Assess the feasibility of using wearable inertial sensors to monitor gait parameters; and evaluate diet self-monitoring apps to evaluate participant engagement and weight loss effectiveness.
The research in this plan integrates with the larger mission of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, and many projects involve internal cross-team collaborations that contribute invaluable multi-disciplinary expertise to the complexities of aging and nutrition research.
Progress Report
Our first objective is to define the impact of foods and specific food components on healthy aging through a variety of human study designs. We have assembled and reviewed the data from the Boston Puerto Rican Osteoporosis Study to ensure completeness. We will conduct future analysis to determine whether there is an association between dairy intake and bone quality. We assessed dairy intake using a food frequency questionnaire, evaluated bone strength using an anterior tibial indentation procedure, and assessed bone architecture using trabecular bone score (TBS) measured on dual energy X-ray absorptiometry scans of the spine. Based on evidence that vitamin K-dependent mechanisms are implicated in osteoarthritis, we initiated a feasibility trial to pilot test procedures and assess the viability of implementing a larger-scale definitive clinical trial of vitamin K supplementation in adults with mild to moderate knee osteoarthritis. To date, we have randomized 34 participants and 23 have completed the 6-month intervention. To achieve our target enrollment of 35, we plan to enroll and randomize 4-6 additional participants.
Our second objective is to explain mechanisms of action and identify physiological processes by which foods and their components mitigate age-related chronic diseases. Dietary omega-3 fatty acids, which are abundant in fish, are converted to specialized pro-resolving lipid mediators (SPMs) that have strong anti-inflammatory activities. To assess whether these SPMs modify the gut microbiome and affect inflammation and atherosclerosis, we studied mice with or without the 15 lipoxygenase (15Lox) gene, randomized to 5 different diets for 16 weeks. A high-fat diet caused a significant increase in serum lipids, pro-inflammatory cytokines, and aorta atherosclerosis in all the mice. However, the omega-3 fatty acids lowered atherosclerosis in the female mice lacking the15Lox gene. The composition of the gut microbiota changed, characterized by lower Bifidobacterium and higher Clostridium, and lower cecum short chain fatty acids content in those mice lacking the 15Lox gene. These results support the concept that the beneficial effects of omega-3 fatty acids on cardiovascular disease are in part mediated by 15Lox through the gut microbiome.
We also initiated an in vitro experiment using mouse colonic organoids to assess the anti-inflammatory and anti-carcinogenic effects of chitin and chitosan, two major components of an insect’s exoskeleton, on biomarkers of inflammation and suppression of cancer-promoting cellular pathways. We completed sample collection and are in process on endpoint analysis. Recently, there has been considerable interest in the potential value of introducing protein-rich insect-based foods into the food supply, for which a nascent market has developed. The results of this work will serve as a basis for designing an in vivo efficacy trial.
Additionally, we designed a human feeding study to address the controversies surrounding the effect of dairy fat, with and without fermentation, on cardiometabolic risk factors. We also want to determine if these effects are mediated by changes in the gut microbiome and gut derived metabolites. To do this, we are conducting a randomized-controlled cross-over trial designed to compare the effects of 2 servings/day for 3-weeks each of full-fat dairy (milk), fat-free dairy (milk), full-fat fermented dairy (yogurt), and fat-free fermented dairy (yogurt). We have successfully recruited all study participants. Seventeen participants have completed all four trial phases, and three are still in the active study. Sample and data analyses will start as soon as the final participant completes the trial. It is anticipated that conducting this trial will increase insights into the crosstalk between host diet, gut microbiome, gut and serum metabolome and indicators of cardiometabolic health.
Our third objective seeks to identify, develop and evaluate assessment tools and biomarkers of diet quality and physical activity that reflect healthy aging. To do this, we are evaluating wearable inertial sensors to assess gait parameters in nutrition intervention studies. There has been a delay in assessing the feasibility of these sensors due to technical reasons reported by our collaborators who are developing them. It is anticipated that the causes of the technical delay will soon be resolved, and recruitment will commence in the fall. These sensors could be particularly valuable in collecting objective data on interventions for osteoarthritis.
Accomplishments
1. Obesity may extend the time required to reach a steady-state vitamin D level. Obesity is linked to having lower levels of vitamin D, but whether obesity influences the time to reach a stable vitamin D level after starting vitamin D supplementation is unknown. ARS-funded scientists in Boston, Massachusetts, studied how long it takes for vitamin D levels to become stable after starting vitamin D supplementation in people with different body weights (normal, over-weight and obese) who participated in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) clinical trial. They found that overweight and obese people need more time to reach stable vitamin D levels compared to the usual 3 months commonly used in clinical practice. This indicates that clinicians need updated guidance on how vitamin D levels respond to supplementation in overweight and obese people to monitor their vitamin D status effectively.
2. Bacterially produced vitamin K does not improve bone quality or bone mineral density during skeletal development in mice. Most research about vitamin K and bone health has focused on the plant-based vitamin K form. However, several other forms of vitamin K are produced by bacteria and are abundant in the intestinal microbiome. Interest in bacterially produced forms of vitamin K is growing because prior research has linked the intestinal microbiome to bone health. ARS-funded researchers in Boston, Massachusetts, evaluated the effect of a bacterially produced form of vitamin K on skeletal health in growing mice. They found that the vitamin K form was absorbed but did not improve bone tissue quality or density. These findings do not support a protective role for vitamin K in skeletal health.
3. Omega-3 fatty acid-derived lipid mediators reduce inflammation in older men and women with high risk of cardiovascular disease. Taking additional omega-3 fatty acids, which are found in fish, reduces inflammation and lowers the risk of heart disease. Our body converts omega-3 fatty acids into other molecules called pro-resolving lipid mediators, which are even better at reducing inflammation than the omega-3 fatty acids they come from. However, it's not known whether eating an average amount of fish can lead to producing enough of these helpful molecules. ARS-funded researchers in Boston, Massachusetts, found that lipid mediators from omega-3 fatty acids in fish can reduce inflammation in older men and women who are at high risk of cardiovascular disease.
Review Publications
Kanis, J.A., Johansson, H., Mccloskey, E.V., Liu, E., Schini, M., Vandenput, L., Akesson, K., Anderson, F.A., Azagra, R., Bager, C., Beaudart, C., Bishchoff-Ferrari, H., Biver, E., Bruyere, O., Cauley, J.A., Center, J.R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C.J., Cummings, S.R., Da Silva, J.A., Dawson-Hughes, B., Diez-Perez, A., Dufour, A.B., Eisman, J.A., Elders, P.J., Ferrari, S., Fujita, Y., Fujiwara, S., Gluer, C., Goldshtien, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R., Huisman, M., Iki, M., Ish Shalom, S., Jones, G., Karlsson, M.K., Khosla, S., Kiel, D.P., Koh, W., Koromani, F., Kotowicz, M., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mcguigan, F.E., Mellstrom, D., Merljin, T., Nguyen, T.V., Nordstrom, A., Nordstrom, P., O'Neill, T., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E., Pasco, J.A., Rivadeneira, F., Schott, A., Shiroma, E.J., Siggeirsdottir, K., Simonsick, E.M., Sornay-Rendu, E., Sund, R., Swart, K., Szulc, P., Tamaki, J., Torgenson, D.J., Van Schoor, N.M., Van Staa, T., Vila, J., Wright, N.C., Yoshimura, N., Zillikens, M., Zwart, M., Harvey, N.C., Lorentzon, M., Leslie, W.D. 2025. Rheumatoid arthritis and subsequent fracture risk: an individual person meta-analysis to update FRAX. Osteoporosis International. https://doi.org/10.1007/s00198-025-07397-1.
Solano Aguilar, G., Matuszek, G.H., Matthan, N., Lichtenstein, A.H., Wang, X., Lakshman, S., Barger, K., Bennett, R., Hyman, B.T., Lamon-Fava, S. 2024. Differential regulation of brain blood vessel transcriptome and brain metabolome by Western and heart-healthy diets in Ossabaw pigs. Scientific Reports. https://doi.org/10.1038/s41598-024-81321-1.