Aging affects nearly every system in the body and is a major driver of chronic degenerative and age-related diseases. The retina, as a highly specialized neural tissue responsible for vision, is particularly vulnerable to age-associated structural and functional decline. Recent preclinical findings suggest that targeting cellular senescence may offer a novel strategy for protecting retinal health. Procyanidin C1 (PCC1), a polyphenolic flavonoid found in grape seed extract, has been reported to possess senolytic and senomorphic activities. New research published in PNAS demonstrates that PCC1 can alleviate age-related retinal deterioration in both structure and function. Together with earlier lifespan studies in mice, these findings position PCC1 as a promising candidate for further investigation in age-related retinal disorders, while emphasizing the need for continued rigorous scientific validation.
Aging influences multiple systems of the body and contributes to the development of chronic degenerative and age-related diseases. As an essential component of the visual system, the retina is not spared from this process.
The retina is composed of finely interconnected layers of specialized neurons. Natural aging leads to a gradual decline in retinal function and structure, which can ultimately result in irreversible blindness and visual impairment.
Encouraging results have been observed in preclinical studies using anti-aging drugs to treat age-related retinal diseases. However, most available compounds act on only a single target, which significantly limits their therapeutic effectiveness.
Procyanidin C1 (PCC1), a polyphenolic compound identified among the flavonoids in grape seed extract, has been shown to possess multiple anti-aging properties. Whether PCC1 can improve the aged retina has remained unclear.
Recently, a research team from the Zhongshan Ophthalmic Center at Sun Yat-sen University published a study in PNAS titled “Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.”
This study verified the anti-aging function of PCC1 through both in vivo and in vitro experiments and demonstrated that PCC1 significantly improves age-related retinal damage.
Functional and Structural Changes in the Aging Retina
To explore how aging affects retinal function, researchers recorded electroretinograms (ERG) from young mice (6–8 weeks old) and aged mice (18–20 months old). ERG responses were found to decline progressively with age.
As aging advanced, multiple retinal structures and functions were impaired, accompanied by the accumulation of senescent cells (SnCs) and increased levels of senescence-associated secretory phenotype (SASP) factors. These inflammatory and tissue-remodeling molecules are widely recognized as contributors to age-related tissue dysfunction.
Cellular senescence in the retina is now considered an important biological driver of degeneration. Senescent cells no longer divide but remain metabolically active, releasing pro-inflammatory cytokines, proteases, and growth factors that can disrupt the surrounding microenvironment. In neural tissues such as the retina, this chronic low-grade inflammation may accelerate functional decline.
PCC1 as a Senotherapeutic Candidate
Researchers then investigated the anti-aging effects of PCC1. Multiple retinal cell lines were used to test its efficacy in vitro. PCC1 treatment markedly reduced cellular senescence across different cell types. In vivo experiments further showed that mice treated with PCC1 exhibited significantly lower levels of senescence markers and SASP-related characteristics.
These findings are consistent with earlier research on PCC1 derived from grape seed extract. PCC1 has been identified as both a senolytic agent, capable of selectively eliminating senescent cells, and a senomorphic agent, able to suppress harmful SASP factors without killing the cells outright. Such dual activity is particularly relevant in complex tissues like the retina, where preserving viable cells while removing dysfunctional ones may be crucial.
In summary, the study mapped the changing cellular composition and phenotypes during natural retinal aging and confirmed through both in vivo and in vitro experiments that PCC1 improves the condition of the aged retina. Specifically, PCC1 can selectively clear SnCs and inhibit SASP. These findings suggest that PCC1 may be a promising therapeutic candidate for age-related retinal diseases.
It is also worth noting that a previous study led by Professor Yu Sun’s team at the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, published in Nature Metabolism, reported that the flavonoid procyanidin C1 has senotherapeutic activity and extends lifespan in mice. That research showed that PCC1, a natural compound from grape seeds, can target pro-aging cells and improve healthspan and lifespan in aged mice.
Grape seed extract has long been studied for its rich content of proanthocyanidins, compounds known for antioxidant and vascular-protective properties. PCC1 represents a more specific, structurally defined molecule within this family, drawing increasing attention for its potential role in modulating fundamental aging mechanisms rather than only providing general antioxidant support. Even so, current evidence remains largely preclinical, and careful clinical evaluation will be essential before translating these findings into human health applications.
References
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Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina. PNAS.
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The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nature Metabolism.