About

Cristal M. Hill, PhD, is an Assistant Professor of Gerontology and serves as the Principal Investigator at the USC Leonard Davis School of Gerontology. Her research focuses on the impact of diet on endocrine systems during aging. She is based in Birmingham, Alabama, and her work contributes to understanding how nutritional factors influence aging processes, particularly through endocrine pathways.

Research topics

• Medicine
• Internal medicine
• Optics
• Physics
• Nuclear medicine
• Psychiatry
• Nursing
• Gerontology

Selected publications

• Dietary Protein Restriction Ameliorates Cardiac Inflammaging via <scp>AMPK</scp> ‐ <scp>ULK1</scp> ‐Mediated Mitochondrial Quality Control

  Aging Cell · 2026-01-18 · 1 citations

  articleOpen access

  Calorie restriction (CR) is a robust intervention for improving metabolic health and delaying obesity and age-related diseases, yet its translational utility is limited by adherence challenges and diminished effectiveness later in life. Dietary protein restriction (DPR), which reduces dietary protein without decreasing total caloric intake, has emerged as a promising alternative, yet its cardioprotective potential in the context of obesity and aging remains poorly understood. Here, we demonstrate that DPR mitigates obesity-induced cardiac remodeling and inflammaging by activating the AMPK-ULK1 signaling axis and enhancing mitochondrial quality control. In middle-aged male mice with high-fat diet-induced obesity, 4 months of DPR attenuated cardiac hypertrophy and normalized heart failure markers, independently of FGF21 signaling. Transcriptomic and protein analyses revealed that DPR suppressed the activation of the cGAS-STING pathway, reduced mitochondrial DNA release into the cytosol, and blunted expression of pro-inflammatory mediators, including IRF3 and IFN-γ. DPR also restored mitochondrial dynamics, enhanced mitophagy, and maintained ATP content despite reduced respiratory capacity. Mechanistically, DPR increased AMPK-dependent ULK1 phosphorylation while suppressing mTOR signaling, thereby promoting mitochondrial turnover. These effects were confirmed in cardiomyocytes, where AMPK knockdown abrogated ULK1 activation and mitophagy under conditions of low amino acid availability. Together, these findings uncover a novel mechanism by which DPR attenuates cardiac inflammation and supports mitochondrial homeostasis, highlighting its therapeutic potential for enhancing cardiovascular health during obesity-mediated inflammaging.

  PublisherDOI

• HARNESSING PROTEIN INTAKE AND MICROBIOME INTERACTIONS TO IMPROVE HEALTHSPAN

  Innovation in Aging · 2025-12-01

  articleOpen access1st authorCorresponding

  Abstract Substantial evidence demonstrate that gut dysbiosis affects metabolic health, particularly while advancing in age. Notably, females tend to experience greater age-related comorbidities such as diabetes and neurodegeneration, many of which are driven by metabolic dysfunction and cellular senescence. Previous work from our lab has demonstrated that dietary protein restriction (DPR) induces fibroblast growth factor 21 (FGF21) to improve metabolic health and extend lifespan in male mice. However, the effects of DPR on gut health in aged female mice remains unclear. In this study, we investigate how DPR influences metabolic health and the gut microbiome in aged female mice. Female mice subjected to DPR at 16 months until 22 months of age exhibited notable improvements in metabolic health. Relative abundances of Clostridium were reduced, while Faecalibaculum rodentium and Kineothrix were increased. Gene set enrichment analysis (GSEA) revealed that bacterial groups associated with membrane integrity and metal ion binding were most enriched during DPR.

  PublisherDOI

• Microbiome, Host-pathogen Interactions, and Aging

  Innovation in Aging · 2025-12-01

  articleOpen access1st authorCorresponding

  Abstract

  PublisherOA PDFDOI

• Low protein-induced-FGF-21 signaling remodels adipose tissue on reduced markers of senescence during aging

  GeroScience · 2025-09-29

  articleOpen accessSenior author

  Cellular senescence and metabolic impairment occur during aging, with adipose tissue decline playing a key role in this process. Furthermore, the detriments of aging on adipose tissue function are further exacerbated by obesity. Dietary protein restriction (DPR), without reducing calorie intake, protects against age-related metabolic decline and extends lifespan through the metabolic hormone FGF21. Here, we demonstrate that protein restriction significantly decreases pro-oncogenic and senescence-related markers in adipose tissue, including SASP, Cdkn1a Cdkn1a, and SA-βgal staining. Additionally, mice fed a low-protein diet during diet-induced obesity demonstrated significant decreases in tumorigenic and cell cycle markers compared with mice fed a control protein and high-fat diet, suggesting that a low-protein diet decreases the burden of cellular senescence on adipose tissue in aged mice and aged obese mice. Conversely, mice lacking FGF21 failed to exhibit the benefits of protein restriction on markers of senescence in white and brown adipose tissue. These data demonstrate that protein restriction exerts distinct beneficial effects on white and brown adipose tissue remodeling on senescence and other markers associated with improvements in lifespan and particularly health span. Given the negative impact of cellular senescence on adipose tissue, protein restriction offers a potential dietary intervention to prevent the detriments of cellular senescence on adipose tissue function during obesity and aging.

  PublisherOA PDFDOI

• Protein-Restricted Diets and Their Impact on Metabolic Health and Aging

  Annual Review of Nutrition · 2025-05-13 · 8 citations

  reviewOpen access

  Recent improvements in human longevity have highlighted the challenge of maintaining health throughout extended lifespans. This review examines how organisms regulate nutrient intake and metabolism, focusing on dietary protein's unique role in health and longevity. While caloric restriction enhances longevity, adherence to a low-calorie diet is challenging. Protein restriction represents an alternate nutritional intervention that improves longevity and health in model organisms and may be easier to translate to humans. However, its impacts are complex, and its mechanisms are poorly understood. The beneficial effects of protein restriction on metabolism and longevity may come at a cost to lean mass and physical resilience. Conversely, while public health recommendations often emphasize high protein intake, human epidemiological data and work on model organisms suggest that excessive protein consumption correlates with increased mortality. Understanding this paradox is crucial for developing evidence-based protein intake recommendations that balance longevity with physical performance.

  PublisherDOI

• MACRONUTRIENT BALANCE AND LONGEVITY: MECHANISTIC INSIGHTS OF DIETARY PROTEIN REGULATION ON AGING PHYSIOLOGY `MACRONUTRIENT BALANCE AND LONGEVITY: MECHANISTIC INSIGHTS OF DIETARY PROTEIN REGULATION ON AGING PHYSIOLOGY

  Innovation in Aging · 2025-12-01

  articleOpen access1st authorCorresponding

  Abstract Neuroendocrine systems play a vital role in homeostatic processes that regulate growth, metabolism, and stress responsiveness, among others. In addition, dietary interventions such as CR or altering macronutrients are reported to modify neuroendocrine signaling to benefit health-span and lifespan. There is substantial evidence that reducing dietary protein intake (dietary protein restriction-DPR), without reducing caloric intake, improves glucose homeostasis, increases energy expenditure, and remodels white adipose tissue (WAT) by inducing thermoregulatory markers such as UCP1. Data from our lab shows that DPR robustly improves metabolic health via increased liver-derived FGF21 action in the brain and that DPR increases thermoregulatory genes, thus DPR represents a purely physiological model to study adipocyte biology. Specifically, the experiments in our lab are focused on identifying the potential mechanisms through which reducing protein intake alters cellular and molecular function in adipose tissue that impact metabolic health. The central focus of this work is to further connect the effects of protein intake on the impact of neuroendocrine signaling on aging physiology.

  PublisherOA PDFDOI

• DIETARY PROTEIN RESTRICTION IN AGED MALE MICE REDUCES MARKERS OF SASP IN ADIPOSE TISSUE

  Innovation in Aging · 2024-12-01

  articleOpen accessSenior author

  Abstract Aging is associated with cellular senescence and metabolic impairment of adipose tissue. Moreover, the detriments of aging are further exacerbated by obesity on metabolic function in adipose tissue. Our lab and others have shown that dietary protein restriction (DPR), without reducing calorie intake, protects against age-related metabolic decline and improves lifespan. To determine if DPR reduces cellular senescence in adipose tissue during aging and aging with obesity, 16 month old male C57BL/6 mice were fed either a normal-protein (20%), low-protein (5%), high-fat (60% fat) or a low-protein/high fat (5% protein; 60%fat) diet for 24-weeks, then adipose depots were analyzed via real time quantitative PCR (RT-qPCR) for cellular senescence markers. We found significant decreases in p21, senescence associated secretory phenotype markers(SASP) and reduced SA-Bgal staining in adipose tissue of mice that were fed a low protein diet compared to normal protein diet fed mice. Additionally, mice on a low protein diet and high fat diet demonstrated significant decreases in cellular senescence markers compared to mice on a normal protein and high fat diet, suggesting that a low protein diet decreases the burden of cellular senescence on adipose tissue in aged mice and aged obese mice. Overall, these data suggests that DPR reduces the burden of cellular senescence on adipose tissue function during aging and aging with obesity. Given the negative impact of cellular senescence on adipose tissue, DPR offers a potential dietary intervention to prevent the detriments of cellular senescence on adipose tissue function during aging and aging with obesity.

  PublisherOA PDFDOI

• The Future is Now - Emerging Trends in the Older Adult.

  PubMed · 2024-01-01

  article

  Expert insight on nutrition and healthy aging along with concise takeaways for practitioners were developed from the 8th Annual Virtual Conference of the Healthy Aging Dietetic Practice Group. With six distinguished professionals presenting on an array of topics, the conference highlighted both emerging trends and advances in the field. The first presentation explored the safe implementation of a low-carbohydrate diet, elucidating its effects on metabolic health and discussed both the best uses and contraindications. The second lecture focused on continuous glucose monitoring in older adults with diabetes, emphasizing the role of technology in improving glycemic control and patient outcomes. In the third expert lecture, the adaptation of the Diabetes Prevention Program (a landmark lifestyle intervention) for older adults was presented, underscoring the need for tailored, age-specific strategies and tactics. The fourth lecture addressed the importance of providing culturally appropriate patient care in dietetics, highlighting the nuances of dietary habits across diverse cultures and cuisines. In the fifth presentation, the speaker deconstructed the concept of "anti-aging" or longevity diets, separating fact from fiction and providing evidence-based insights into emerging nutritional therapies to extend lifespan, including controversial dietary approaches with evolving science like protein restriction and calorie restriction. The conference wrapped up with a discussion on the aging brain, highlighting the relationship between nutrient-rich diets and cognitive function in older adults, including key micronutrient needs and the impact of multivitamin supplementation. Overall, the conference served as a platform for knowledge exchange and emphasized the pivotal role of dietetics in promoting healthy aging and longevity.

  Publisher

• The Future is Now - Emerging Trends in the Older Adult

  PubMed Central · 2024-07-31

  articleOpen access
  PublisherOA PDF

• Adaptive Responses After Exposure to Low Dose Radiation

  CRC Press eBooks · 2024

  1st authorCorresponding
  • Medicine
  • Nuclear medicine
  • Physics

  Since the exploding of the first atomic bomb at the end of the second World War there has been an overriding and all-pervading concern about the deleterious effects of radiation. These concerns have led to radiation sources of all types being, perhaps, the most closely regulated of potentially toxic substances in modern society. However, despite this notoriety, radiation of various kinds occupies an important niche in our society, particularly in medicine, where x-rays and nuclear isotopes, for example, have vastly improved diagnostic abilities and thus the quality of our health in general.

  DOI

Recent grants

• NIH Grant R01CA033974

  NIH · $853k · 1989

• NIH Grant R01CA042808

  NIH · $1.6M · 1994

Frequent coauthors

• M. M. Elkind

  Tel Aviv University

  29 shared

• A. Han

  18 shared

• Jay Nadeau

  Portland State University

  9 shared

• Konstantin Kudinov

  9 shared

• Stephen E. Bradforth

  University of Southern California

  9 shared

• Daniel R. Cooper

  McGill University

  8 shared

• Nobuo Kubota

  Pola Chemical Industries (Japan)

  6 shared

• M. Ikebuchi

  5 shared

Labs

• The Hill LabPI

Education

• Ph.D., Molecular Biology

  Southern Illinois University

  2022

• M.S., Animal and Poultry Sciences

  Tuskegee University

  2016

• B.S., Animal Sciences

  Tuskegee University

  2010