Melatonin, Lipofuscin, and Age-Related Neurodegeneration: Reflections on Light at Night

[Source: Litvinenko, G. I.; Gritsyk, O. B.; Mel’nikova, E. V.; Avrorov, P. A.; Tenditnik, M. V.; Shurlygina, A. V.; Trufakin, V. A. Changes in the Interaction of the Pineal Gland and Immune System Organs in Rats in Response to Administration of Melatonin in Conditions of an Altered Light Regime. Neurosci. Behav. Physiol. 2016, 46, 882–887]

Today’s story on melatonin is inspired by a recent peer-reviewed study that showed the important role played by a common autofluorescent pigment called lipofuscin in age-related neurodegeneration and traumatic brain injury in animal models [Ritzel et al. 2023].

Lipofuscin is a non-degradable substance formed as a result of oxidative processes involving metals such as iron, proteins and lipids. Lipofuscin can become excited by light and become fluorescent. Autofluorescence from endogenous molecules such as lipofuscin is an intrinsic property of the molecule, and should not be confused with fluorescent signals that can be obtained by adding exogenous markers [Monici 2005].

As an animal ages, the amount of lipofuscin is increased because this pigment cannot be degraded or removed [Terman and Brunk 2004]. When lipofuscin is excited by light, it can generate free radicals such as superoxide anions in a dose-dependent manner. The binding between this autofluorescent pigment and transition metals such as iron and copper can further sensitize cells to oxidative stress [Boulton et al. 1993].

Why is exposure to light an important factor in lipofuscin pathology?

The story is really quite simple. When exposed to light, especially at night, lipofuscin accumulates in the pineal gland and can cause cell death in the pineal gland. The pineal gland synthesizes melatonin in animals at night.

Exposure to any amount of light can suppress pineal production of melatonin at night [Prayag 2019]. This particular insult is a recent modern development. Before the advent of electricity, intense light at night was non-existent.

What are the ramifications of light at night and lipofuscin pathology?

Nature has established a perfect solution to protect animals from the deleterious effects of bright light exposure in the daytime that can activate lipofuscin by producing melatonin to suppress the formation.

Animal experiments found that continuous light exposure not only suppressed pineal melatonin production at night, but also dramatically increased the accumulation of lipofuscin in the pineal gland (see article photo above)…