Longevity research into metabolic diseases is heating up

Accumulating evidence suggests that targeting the thermogenic adipose tissue decline during aging may prevent age-related metabolic and inflammatory disorders.

In humans and other warm-blooded animals, brown and subcutaneous adipose tissues serve as energy storage units used for heat production during the cold periods. This process of “burning” adipose tissue for heat production is also known as non-shivering thermogenesis and is key to maintaining physiological body temperatures and the survival of organisms.

Longevity.Technology: Thermogenesis is tightly regulated by various hormones, which induce lipid breakdown – also known as lipolysis – for the production of energy and heat. Hence, activation of thermogenesis reduces the lipid content of our tissues and has been associated with a lower risk of type 2 diabetes and other age-related metabolic disorders.

Increasing evidence supports a link between aging, type 2 diabetes, chronic low-grade inflammation, and thermogenic adipose tissue decline. However, the age-associated metabolic and immune alterations leading to type 2 diabetes remain poorly understood [1, 2].

Accumulating evidence suggests that targeting the thermogenic adipose tissue decline during aging may prevent age-related metabolic and inflammatory disorders.
The team at the University of Rome Tor Vergata Dept. Biology. Source: Daniele Lettieri Barbato, PhD

As described in a recent review article by Daniele Lettieri-Barbato and Katia Aquilano, exciting new evidence shows that thermogenic adipose tissue activation polarizes immune responses towards type 2 immunity. These findings suggest that reduced thermogenesis during aging may increase the risk of type 2 diabetes in the elderly by promoting chronic low-grade inflammation termed “inflammaging”. The review article appears in the November 2020 issue of the journal Ageing Research Reviews [3].

During thermogenesis, adipocytes undergo extensive metabolic reprograming characterized by increased glucose and succinate uptake, as well as enhanced glycolysis and lipolysis – resembling the metabolic rewiring observed in activated inflammatory cells. The shared energetic substrates and metabolic pathways between activated adipocytes and inflammatory cells suggest an important anti-inflammatory role for thermogenic adipocytes [3].

In addition to the anti-inflammatory effect of thermogenesis due to nutrient competition, thermogenic adipose tissue activation in response to cold exposure induces the release of eosinophil-activating cytokines by type 2 innate lymphoid cells. Subsequent IL-4 release by eosinophils contributes to the establishment of an anti-inflammatory state characterized by high levels of IL-10 and M2 macrophages [3].

Technologies and tools for investigating the metabolic phenotype of immune cells resident in thermogenic adipose tissues. Source: Department of Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, 00133, Rome, Italy

Therefore, the reduction in adipose tissue content and activity in our body during aging may contribute to inflammaging and insulin resistance, increasing the susceptibility of older individuals to immunometabolic diseases, including type 2 diabetes, cancer, and infections.

Although exercise, intermittent cold exposure and low-calorie intake may extend healthy life by preventing the loss of thermogenic adipose tissues, thermogenesis-modulating interventions to promote Longevity are currently lacking. Future studies are required to elucidate the complex physiological processes linking the thermogenic adipose tissue decline to immunometabolic dysfunction during aging. Only then will we be able to target thermogenic adipose tissue decline to treat age-related metabolic disorders and promote healthy aging.

[1] https://www.frontiersin.org/articles/10.3389/fimmu.2018.00169/full
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702504/
[3] https://www.sciencedirect.com/science/article/pii/S1568163720302786

Images courtesy of University of Rome Tor Vergata, Dept. Biology and Skitterphoto / Pexels