‘Skinspan’ Framework Developed to Extend Skin Longevity, Prevent Aging

An evidence-based, first-line approach combining sun protection, topical retinoids, and antioxidants may be effective in promoting skin longevity, according to recent findings.1

These findings further suggest the need for second-line interventions involving skin-protecting procedures such as laser and energy-based devices. Elizabeth Kream, MD, of Cosmetic Laser Dermatology in San Diego, led the investigators who authored the review that led to such results. Their review’s purpose was to present the concept of “skinspan” as a framework for skin vitality sustenance throughout patients’ lives.

Kream et al noted that phenotypic shifts in the skin of different individuals are impacted by a combination of intrinsic and extrinsic factors.2 These factors, the investigators noted, will converge on shared molecular pathways that can then disrupt the homeostasis of one’s skin over time.

“While the term ‘skinspan’ has been coined in informal contexts, to our knowledge, this publication represents the first instance of the term being introduced in peer-reviewed literature, accompanied by recommendations for its integration into clinical practice,” Kream and colleagues wrote.1 “This paper reviews core molecular mechanisms of skin aging along with how these hallmarks are targeted through proactive interventions, altogether extending skinspan.”

Review Details

The investigators' review synthesizes data from available literature on the topic of molecular hallmarks of skin aging. These hallmarks included mitochondrial decline, genomic instability, cellular senescence, and impaired proteostasis. In their review, Kream and colleagues focused on the manner in which such processes can be addressed via lifestyle strategies, pharmacologic interventions, and even aesthetic procedures.

In their review, they highlighted a variety of data on this topic. The team first noted that, at the molecular level, aging begins with the accumulation of cellular damage. Skin cells are frequently exposed to ultraviolet radiation (UVR) as well as environmental pollutants and endogenous metabolic byproducts. Such impacts can lead to progressive dysfunction in cellular repair and signaling.

While there are natural defense mechanisms, Kream and colleagues highlighted that their capacity declines with advancing age. For example, animal models with defective mitochondrial polymerase develop premature aging. This underscores the role of mitochondrial integrity in maintaining one's tissue health. Similarly, fibroblasts that have entered senescence are known to produce less insulin-like growth factor 1 (IGF-1), impairing the ability of keratinocytes to recover from UV-induced damage to DNA.

The investigative team further suggested that senescent cells may develop a pro-inflammatory secretory profile, described as the senescence-associated secretory phenotype (SASP). This includes cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α. The SASP spreads senescence to neighboring cells, which the team note contributes to wrinkling and higher perceived age.

UVR was described in the review as the most significant external variable on skin aging. Kream and coauthors noted that UVA penetrates deeper to alter fibroblast gene expression. Other factors can affect this process, including cigarette smoke, which promotes oxidative stress, disrupts autophagy, and weakens fibroblast function. Additionally, airborne pollutants such as gases and particulates can induce DNA damage and lipid peroxidation. The investigators noted that both mechanistic and epidemiologic data support pollution as a contributor to pigmentation irregularities and wrinkle increases.

Findings on Preventing Skin Aging

Kream and colleagues highlighted a plethora of interventions which have been assessed to counter drivers of skin aging. They expressed in their review that lifestyle-based approaches, topical options, systemic medications, and minimally invasive procedures can all play a role in preserving skinspan. The authors recommended a tiered approach to management.

In light of the findings described in their review, first-line strategies Kream et al emphasized included preventive and foundational measures: diligent photoprotective measures, the implementation of topical retinoids, and the use of antioxidant therapies. Such strategies, they noted, can serve as the cornerstone for mitigating cumulative molecular damage.

In assessing any second-line options, the investigative team pointed to energy-based technologies such as lasers. Beyond such measures, the team highlighted emerging third-line interventions which are being investigated, including stem cell–derived therapies, agents that target sirtuins, nicotinamide, and naturally occurring SIRT activators. While promising, the investigators noted that such interventions are still in the experimental phase and will require continued monitoring of evidence.

Overall, Kream and coauthors' skinspan model highlights the interplay of intrinsic biology and environmental stressors in shaping the health of one's skin across one's lifespan. Preventive measures intergrated with targeted therapies may help clinicians to delay age-related changes and preserve skin function.

“Skinspan also illuminates the synergism of procedural, medical, and lifestyle interventions, many of which confer benefits beyond the skin,” the investigative team concluded.1 “Building on the canon of in vitro and in vivo studies, more randomized clinical trials are needed to strengthen the evidence base, especially as new therapeutic candidates continue to emerge.”

References

1. E Kream, SG Fabi, M Boen. Skinspan: A Holistic Roadmap for Extending Skin Longevity With Evidence-Based Interventions. Journal of Cosmetic Dermatology 24, no. 9 (2025): e70432. https://doi.org/10.1111/jocd.70432.

2. Jin S, Li K, Guo S, et al. Hallmarks of Skin Aging: Update. Aging Dis. 2023 Dec 1;14(6):2167-2176. doi: 10.14336/AD.2023.0321. PMID: 37199583; PMCID: PMC10676801. Accessed September 12, 2025.