Biomaterial Database

An aging-susceptible circadian rhythm controls cutaneous antiviral immunity. 2023

Stephen J Kirchner, and Vivian Lei, and Paul T Kim, and Meera Patel, and Jessica L Shannon, and David Corcoran, and Dalton Hughes, and Diana K Waters, and Kafui Dzirasa, and Detlev Erdmann, and Jörn Coers, and Amanda S MacLeod, and Jennifer Y Zhang

Department of Dermatology.

Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced levels of antiviral proteins (AVPs) and circadian regulators, including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin, and such circadian control of AVPs was diminished by disruption of immune cell IL-27 signaling and deletion of Bmal1/Clock genes in mouse skin, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment with the circadian-enhancing agents nobiletin and SR8278 reduced infection of herpes simplex virus 1 in epidermal explants and human keratinocytes in a BMAL1/CLOCK-dependent manner. Circadian-enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.

UI	MeSH Term	Description	Entries
D002940	Circadian Rhythm	The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli.	Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012867	Skin	The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D015603	Keratinocytes	Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.	Keratinocyte
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056930	ARNTL Transcription Factors	Basic helix-loop-helix (bHLH) domain-containing proteins that play important roles in CIRCADIAN RHYTHM regulation. They combine with CLOCK PROTEINS to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation.	ARNTL1 Protein,ARNTL2 Protein,Aryl Hydrocarbon Receptor Nuclear Translocator-like 1 Protein,Aryl Hydrocarbon Receptor Nuclear Translocator-like 2 Protein,Aryl Hydrocarbon Receptor Nuclear Translocator-like Protein 1,Aryl Hydrocarbon Receptor Nuclear Translocator-like Transcription Factors,BMAL1 Protein,BMAL2 Protein,Brain and Muscle ARNT-like 2 Protein,Brain and Muscle ARNT-like Proteins,Brain and muscle ARNT-like 1 Protein,MOP3 Transcription Factor,MOP9 Transcription Factor,Member of PAS Protein 3,Member of PAS Protein 9,Aryl Hydrocarbon Receptor Nuclear Translocator like 1 Protein,Aryl Hydrocarbon Receptor Nuclear Translocator like 2 Protein,Aryl Hydrocarbon Receptor Nuclear Translocator like Protein 1,Aryl Hydrocarbon Receptor Nuclear Translocator like Transcription Factors,Brain and Muscle ARNT like 2 Protein,Brain and Muscle ARNT like Proteins,Brain and muscle ARNT like 1 Protein,Transcription Factor, MOP9,Transcription Factors, ARNTL