Could Lasers and Energy‐Based Devices Be Considered a Gerotherapeutic?

The consequences of skin aging are often dismissed as simply a cosmetic concern. Lasers and other energy‐based devices are primarily framed as modalities to improve the appearance of skin and rejuvenate the way it looks, a framing justified by the primary outcomes of clinical studies and marketing of these tools. However, a broader and more consequential possibility is that skin aging may contribute to systemic inflammation and multi‐organ dysfunction. In this view, skin aging itself may be a modifiable risk factor for age‐related diseases, positioning interventions that improve skin health as potential strategies to extend not only “skingevity,” but overall longevity. To that end, controlled wounding therapies that induce hormetic responses in the skin, such as lasers and energy‐based devices, may hold promise as gerotherapeutics.

To set the stage, it is important to consider developments from Geroscience, a field that has gained momentum following the identification of the hallmarks of aging [1]. Geroscience operates on the principle that age itself is the primary risk factor for chronic diseases, and that targeting shared biological mechanisms of aging via gerotherapeutics may simultaneously mitigate multiple age‐related conditions. These hallmarks are deeply interconnected, linked via shared signaling pathways and feedback loops, such that modulation of one pathway may influence others. Among these, chronic inflammation, termed “inflammaging,” has emerged as a central hallmark of aging.

Inflammaging is characterized by the chronic, low‐grade rise in sterile inflammation that accompanies aging. Old blood increasingly has proinflammatory cytokines and other “old” blood‐related factors that contribute to multi‐organ aging [2, 3, 4]. Systemic inflammaging predicts cardiovascular disease, neurodegeneration, metabolic syndrome, sarcopenia, and frailty [5]. This association has been clearly demonstrated in multiple studies. In heterochronic parabiosis and neutral blood exchange studies, exposure of young animals to aged circulation induces neurocognitive decline, tissue dysfunction, and multi‐organ senescence [2, 6]. Whereas, dilution of aged blood via therapeutic plasma exchange (TPE) reduces pro‐inflammatory cytokines, restores a more youthful circulating proteome, and improves tissue repair, functional performance, and cognitive function [7, 8, 9]. Multiple clinical studies also showed benefits with TPE: reduced biological age, DNA damage, and senescence, and restored youthful proteomes [10, 11]. Simply put, old blood into young models induced disease, while diluting old blood conferred health benefits. Collectively, these findings support the concept that circulating factors are both drivers and mediators of systemic aging.

A key upstream contributor to inflammaging is cellular senescence [12]. Senescent cells accumulate with age and remain metabolically active, releasing various proinflammatory cytokines, chemokines, and matrix‐remodeling enzymes, collectively known as the senescence‐associated secretory phenotype (SASP) [13]. The SASP reinforces local inflammation, induces secondary senescence in neighboring and distant cells, and propagates systemic inflammatory signaling [14]. A study showed that senolytic treatment administered to old mice prior to transferring aged blood attenuated the induction of senescence, preserved muscle function, and reduced pro‐inflammatory cytokines in young mice. This suggests that clearing age‐accumulated senescent cells can rejuvenate old circulating blood [6].

Within this model, the skin emerges as a uniquely important organ. As the largest organ in the body and the primary interface with the external environment, the skin is continuously exposed to environmental stressors, including ultraviolet radiation, pollutants, and mechanical injury. With advancing age, the skin undergoes progressive barrier dysfunction, accumulation of senescent cells, and increased secretion of pro‐inflammatory mediators [13]. These cascading events lead to progressively higher levels of circulating pro‐inflammatory cytokines, which mediate organ dysfunction, and position the skin as a significant contributor to inflammaging [12, 15].

Given these considerations, the following framework is posited: aged skin, through barrier dysfunction, senescent cell accumulation, and pro‐inflammatory signaling, acts as a significant upstream driver of systemic inflammaging and multi‐organ dysfunction. If true, treating the skin (barrier repair, senolysis, controlled wounding) to improve skin health and resilience should measurably decrease circulating inflammatory mediators and confer benefits beyond the skin itself.

Studies suggest that skin inflammation/aging may be associated with atherosclerosis, dementia, diabetes, and perceived age [16, 17, 18]. Skin diseases characterized by barrier dysfunction and chronic inflammation, such as atopic dermatitis and psoriasis, are associated with increased cardiovascular risk, morbidity, and mortality [19, 20, 21]. In addition, lower expression of senescence markers, such as p16, in the skin, as well as reduced wrinkling in sun‐protected areas, has been associated with improved longevity and decreased cardiovascular risk [22]. Perceived younger age similarly correlates with increased survival, suggesting that skin appearance may reflect underlying systemic health [23].

Mechanistically, several pathways may explain how skin aging contributes to systemic dysfunction. Barrier dysfunction increases susceptibility to environmental stressors and promotes sustained inflammatory signaling. Senescent skin cells release SASP factors that enter the circulation and propagate dysfunction at distant sites. In a pivotal mouse study, transplantation of senescent fibroblasts into the skin of young mice led to distant multi‐organ dysfunction [24]. Following transplantation, young mice developed senescence in distant tissues (liver, muscle, hippocampus), alongside increased frailty, decreased motor coordination and grip strength, impaired musculoskeletal function, and a significant decline in cognitive function. At 5 months, plasma IL‐6 remained significantly elevated. Whereas mice transplanted with non‐senescent fibroblasts were unaffected [24]. In addition, skin aging may be associated with age‐related bone loss [25]. Bone resorption increases with age, and its effects are evident in the aging face, as the maxillary angle decreases and the orbital aperture widens. Cystatin A (Csta) is a factor released from keratinocytes that maintains bone turnover. With age, Csta decreases in human and mouse skin. In young mice with epidermal Csta knockout, bone turnover was low, mimicking senile osteoporosis, whereas epidermal overexpression of Csta rescued bone mass loss [25]. These data suggest that the senescent burden in the skin is sufficient to propagate functional decline systemically.

Importantly, interventions that improve skin barrier function and reduce skin inflammation have been shown to decrease systemic inflammatory markers. In animal and human studies, acute barrier disruption and age‐related barrier dysfunction increase plasma inflammatory cytokines, whereas restoration of barrier function significantly reduces these levels [26]. Clinically, a 30‐day full‐body emollient trial significantly reduced plasma IL‐1, IL‐6, and TNF‐alpha to youthful levels [27]. In addition, a recent clinical trial evaluated the efficacy of a topical senotherapeutic (OS‐01) and found a significant decrease in plasma IL‐8 and stabilized biological age [28]. These studies support that improving skin health reduces systemic inflammaging.

These findings raise an important translational question: if skin aging via senescent cell accumulation and barrier dysfunction contributes to inflammaging, could therapies traditionally used for cosmetic rejuvenation, such as lasers and energy‐based devices, exert broader systemic benefits? TPE offers a promising method to reduce inflammaging by clearing circulating pro‐aging factors. However, this approach addresses downstream mediators rather than their source. In contrast, targeting senescent cells represents an upstream strategy aimed at reducing the production of pro‐inflammatory factors. This distinction is critical, as interventions that reduce the source of systemic inflammation may provide more sustained and clinically practical benefits.

Interestingly, emerging evidence suggests that existing tools may already target these upstream mechanisms. A recent systematic review found that all lasers and energy‐based devices evaluated reduced skin senescence [29]. Fractional ablative CO₂, Er:YAG, and 2910‐nm lasers have been shown to decrease markers of senescence and normalize IGF‐1 to restore appropriate UV‐damage response in the skin, effectively reducing the risk of future neoplasia. In addition, radiofrequency microneedling and ultrasound‐based devices decrease senescent markers and restore appropriate cell‐to‐cell signaling. These effects are thought to arise from controlled wounding and hormetic stress responses that promote cellular turnover, enhance repair pathways, and potentially facilitate clearance or remodeling of senescent cells [29].

By reducing cell senescence, laser‐ and energy‐based treatments may also reduce inflammaging and multi‐organ dysfunction. This reframes these devices not solely as cosmetic interventions but as a potential gerotherapeutic that reduces the systemic inflammatory burden by targeting the skin, potentially conferring longer‐term systemic benefits. This raises the need to investigate larger‐surface or full‐body treatments to assess whether comprehensive skin rejuvenation can be a gerotherapeutic strategy.

Future research should focus on quantifying the systemic impact of large‐scale skin‐targeted interventions using multi‐omic approaches, including circulating cytokine profiling, senescent cell burden, epigenetic clocks, and proteomic aging signatures. While this strategy has many limitations and practical barriers (cost, time, downtime, etc.) and is unlikely to be widely implemented, this approach may offer valuable proof‐of‐concept models for understanding the role of the skin in systemic aging.

Skin aging is increasingly recognized as a biologically active process that contributes to systemic inflammation and age‐related organ dysfunction. Far from being a purely cosmetic concern, skin aging involves barrier dysfunction, accumulation of senescent cells, and the chronic secretion of pro‐inflammatory mediators. Reframing the skin as a modifiable risk factor for systemic aging suggests that skin rejuvenation via lasers and energy‐based devices may confer benefits that extend beyond appearance, moving past the current era of regenerative aesthetics to encompass systemic health and longevity as a gerotherapeutic approach.

Conflicts of Interest

The author declares no conflicts of interest.

Data Availability Statement

The author has nothing to report.