The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective

It is widely accepted that nine hallmarks-including mitochondrial dysfunction, epigenetic alterations, and loss of proteostasis-exist that describe the cellular aging process. Adding to this, a well-described cell organelle in the metabolic context, namely, lipid droplets, also accumulates with increasing age, which can be regarded as a further aging-associated process. Independently of their essential role as fat stores, lipid droplets are also able to control cell integrity by mitigating lipotoxic and proteotoxic insults. As we will show in this review, numerous longevity interventions (such as mTOR inhibition) also lead to strong accumulation of lipid droplets in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mammalian cells, just to name a few examples. In mammals, due to the variety of different cell types and tissues, the role of lipid droplets during the aging process is much more complex. Using selected diseases associated with aging, such as Alzheimer's disease, Parkinson's disease, type II diabetes, and cardiovascular disease, we show that lipid droplets are Janus-faced. In an early phase of the disease, lipid droplets mitigate the toxicity of lipid peroxidation and protein aggregates, but in a later phase of the disease, a strong accumulation of lipid droplets can cause problems for cells and tissues.

Automated summary

Many hallmarks, including mitochondrial dysfunction, epigenetic alterations, and loss of proteostasis, exist that describe the cellular aging process. In addition, lipid droplets, a well-described cell organelle in the metabolic context, accumulate with increasing age, adding to the aging-associated process. Lipid droplets not only serve as fat stores, but also control cell integrity by mitigating lipotoxic and proteotoxic insults. Longevity interventions, such as mTOR inhibition, lead to strong accumulation of lipid droplets in various organisms. In mammals, lipid droplets play a complex role during the aging process, as they can both mitigate toxicity and cause problems for cells and tissues in different disease states.