‘‘Inflammaging’ is the chronic, low-grade inflammation that arises in many tissues during the aging process. Inflammation is normally beneficial for the body because it facilitates wound healing and the clearance of foreign pathogens. However, with age, control over the release of inflammatory molecules or their cleanup can deteriorate, leading to chronic inflammation- or 'inflammaging'- despite a lack of injury or invaders. Inflammatory genes which contribute to reproductive senescence are upregulated during aging.
What do we know?

What causes inflammaging?

  • Inflammation has downstream physiological consequences (such as fibrosis) in the ovaries that can compromise reproductive function. There are several hypothesized drivers of chronic inflammation under investigation by longevity researchers.
  • Aging of the immune system in general can generate systemic inflammation which may affect ovarian function. Other changes may be more specific to the ovary. Macrophages are one type of leukocyte (immune cell) associated with chronic inflammation in the tissue. Macrophages are important for the function of healthy ovaries, but lose control over the secretion of inflammatory molecules during aging, resulting in sustained low-level inflammation. Recent studies have begun to identify specific age-related changes in ovarian macrophages that contribute to chronic inflammation.
  • Many hallmarks of aging are tightly interconnected. Processes such as mitochondrial dysfunction and cellular senescence (link to each page in the KH) can generate cellular damages that drive an inflammatory response, which can in turn accelerate the onset of other aging hallmarks.
  • The ovulatory cycle itself may also contribute to increased inflammation in the ovaries. Numerous follicles mature during each cycle, but only one or a few are selected for ovulation. The remainder die or degenerate in a process known as atresia, while the selected follicle(s) rupture and release their oocyte into the fallopian tubes. Both of these processes bear some biological similarities to inflammation.
  • Certain conditions, such as obesity and PCOS (link to KH) can also increase chronic inflammation, explaining some of the connection between these conditions and infertility.
  • Altogether, the ovaries are extremely vulnerable to the onset of inflammaging.

What are the results of inflammaging?

  • Oocyte health and the ovarian reserve are sensitive to changes in the local ovarian tissue environment, making fertility especially sensitive to the damages of inflammaging.
  • Most research on this connection is on ovarian tissue fibrosis, where as a result of excessive inflammatory activity, tissue structure and integrity can be compromised. Fibrosis is a hallmark of aging reproductive tissue and contributes to the decline in fertility and function with age. Fibrotic tissue is ‘stiffer,’ containing different structural molecules which both contribute to mechanical difficulties with ovulation and pregnancy and also to altered signaling dynamics that can impair follicular development and oocyte viability.
  • Inflammation may contribute to the development of severe phenotypes such as premature ovarian insufficiency (POI)

What's Next? Big Questions.

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