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Does Aging Activate T-cells to Reduce Bone Mass and Quality?

  • Osteoimmunology (A Pettit and J Charles, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Aging leads to decline in bone mass and quality starting at age 30 in humans. All mammals undergo a basal age-dependent decline in bone mass. Osteoporosis is characterized by low bone mass and changes in bone microarchitecture that increases the risk of fracture. About a third of men over the age of 50 years are osteoporotic because they have higher than basal bone loss. In women, there is an additional acute decrement in bone mass, atop the basal rate, associated with loss of ovarian function (menopause) causing osteoporosis in about half of the women. Both genetics and environmental factors such as smoking, chronic infections, diet, microbiome, and metabolic disease can modulate basal age-dependent bone loss and eventual osteoporosis. Here, we review recent studies on the etiology of age-dependent decline in bone mass and propose a mechanism that integrates both genetic and environmental factors.

Recent Findings

Recent findings support that aging and menopause dysregulate the immune system leading to sterile low-grade inflammation. Both animal models and human studies demonstrate that certain kinds of inflammation, in both men and women, mediate bone loss. Senolytics, meant to block a wide array of age-induced effects by preventing cellular senescence, have been shown to improve bone mass in aged mice. Based on a synthesis of the recent data, we propose that aging activates long-lived tissue resident memory T-cells to become senescent and proinflammatory, leading to bone loss. Targeting this population may represent a promising osteoporosis therapy.

Summary

Emerging data indicates that there are several mechanisms that lead to sterile low-grade chronic inflammation, inflammaging, that cause age- and estrogen-loss dependent osteoporosis in men and women.

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Acknowledgements

We acknowledge the contribution of current and past members of the Aurora and Veis labs to the ideas presented in this review.

Funding

This research was partially supported by NIH under Award Numbers: R01-AR070030 (DV), R01-AI161022 (DV), and P01-CA100730 (DV).

Author information

Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., DRC605, St. Louis, MO, 63104, USA

    Rajeev Aurora

  2. Division of Bone and Mineral Diseases and Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA

    Deborah Veis

Authors
  1. Rajeev Aurora
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  2. Deborah Veis
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Correspondence to Rajeev Aurora.

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Aurora, R., Veis, D. Does Aging Activate T-cells to Reduce Bone Mass and Quality?. Curr Osteoporos Rep 20, 326–333 (2022). https://doi.org/10.1007/s11914-022-00745-8

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