GeroScience study highlights protective role of hemokinin-1 against age-dependent cognitive decline in mice

A new study reveals that hemokinin-1 deficiency in mice accelerates age-dependent declines in spatial memory and attention, identifying the tachykinin family member as a potential protective target for cognitive aging.

Researchers from the University of Pécs and Semmelweis University evaluated the cognitive performance of young (3–5 months), middle-aged (12–15 months), and old (18–20 months) wildtype and hemokinin-1 (HK-1)-deficient (Tac4 knockout) mice.

The team conducted both longitudinal and cross-sectional studies using behavioral assays, including the Barnes maze, radial arm maze, 5-choice serial-reaction time task (5-CSRTT), and fear conditioning.

While young mice of both genotypes successfully acquired spatial tasks, significant genotype-dependent deficits emerged with age in the HK-1-deficient cohorts.

HK-1-deficient mice exhibited impaired long-term spatial memory in the Barnes maze, reduced attentional and reinforcement learning in the 5-CSRTT, and increased memory errors in the radial arm maze.

In contrast, Y-maze spontaneous alternation and novel object recognition assays did not show robust genotype-dependent differences, indicating domain-specific cognitive protection by endogenous HK-1.

Age-related cognitive decline remains a critical biomedical challenge, with existing therapeutic options like cognitive enhancers showing limited clinical efficacy.

Hemokinin-1, the newest member of the tachykinin neuropeptide family, is structurally similar to substance P and is expressed in brain regions essential for memory and learning, such as the cortex, hippocampus, and amygdala.

This study provides the first in vivo evidence that HK-1 plays an active, protective role in maintaining executive functions, attention, and spatial retention during physiological aging.

Because the Tac4 gene is expressed in cholinergic and GABAergic neurons, the findings suggest HK-1 signaling might interact with neurotransmitter systems that typically degenerate during pathological brain aging.

The discovery highlights tachykinin pathway modulation as a potential avenue for novel drug discovery in the cognitive longevity space.

While no clinical-stage longevity biotechs are currently targeting Tac4 or HK-1 directly, the publication reinforces the therapeutic relevance of targeting neuroimmune and neuropeptide networks to preserve cognitive health.

Preclinical pipelines focused on cellular rejuvenation and neuroinflammation may leverage these findings to support the development of multi-target therapies for neurodegenerative conditions.

Further preclinical studies to determine whether pharmacological administration of HK-1 agonists can rescue or reverse age-associated spatial memory and attentional deficits in wildtype aged animal models.