Inflammaging and Cellular Senescence: Emerging Strategies for Skin Longevity
Clinical Summary
Inflammaging and Cellular Senescence: Emerging Targets for Skin Longevity
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Skin aging mechanisms: Cellular senescence promotes the senescence-associated secretory phenotype (SASP), releasing pro-inflammatory cytokines that drive inflammaging; this positive feedback loop accelerates both intrinsic and extrinsic skin aging.
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Emerging therapies: Investigational approaches include senolytics, senomorphics, topical mTOR inhibitors (e.g., rapamycin-based formulations), and immunomodulators (biologics, JAK inhibitors) targeting aging-related pathways.
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Clinical application: Incorporate lifestyle counseling to reduce inflammaging—limit UV exposure, pollution, and environmental stress, while encouraging exercise, Mediterranean-style diets, and reduced advanced glycation end products (AGEs) as part of skin longevity strategies.
Reviewed by Riya Gandhi, MA, Associate Editor of Immunology Group
Dr Helen He discusses how cellular senescence and inflammaging work together to accelerate intrinsic and extrinsic skin aging. Learn how emerging therapies—including senolytics, senomorphics, topical mTOR inhibitors, and immunomodulatory approaches—may target the biology of aging, and discover practical lifestyle and preventive strategies dermatologists can use to promote healthier, longer-lasting skin.
Transcript
My name is Dr Helen He. I am a general and cosmetic dermatologist at Mount Sinai, where I am director of lasers and cosmetic surgery and co-director of the Mount Sinai Clinic Healthy Skin Dermatology Center. I also have a research interest into better understanding the molecular mechanisms that undermine skin aging so that we can develop more targeted and evidence-based therapeutic strategies to stimulate skin longevity.
How do inflammaging and cellular senescence interact to drive both intrinsic and extrinsic skin aging?
Dr He: So when cells in a skin become senescent, they start expressing the senescence-associated secretory phenotype, or SASP. And that includes, among other things, pro-inflammatory cytokines that propagates inflammation. So simultaneously, the downstream effects of those inflammatory cytokines actually lead to further senescence. So this positive feedback loop is a vicious cycle that drives the signaling pathways that are responsible for both intrinsic and extrinsic skin aging, including multiple other hormones of aging.
What emerging therapies—topical or systemic—are showing promise in targeting these pathways at a clinically meaningful level?
Dr He: So several senolytics and phenomorphics are currently being studied. And while many of these are still in preclinical stages, I think there are some exciting developments in the field. So, for example, mTOR is an important pathway in regulating cell growth, cell metabolism, and the aging process as a whole. And then the classic mTOR inhibitor, rapamycin, it's still quite controversial as a systemic therapy. But now there are topical formulations being developed that target mTOR, mTORC1, as well as other synotherapeutic peptides that may be safer and are undergoing clinical studies in human subjects.
Additionally, inflammaging is also now emerging as a promising therapeutic target. So immunomodulatory approaches like biologics or JAK inhibitors are also now being investigated for their potential anti-aging properties.
How can dermatologists begin to incorporate this science into preventive and therapeutic strategies for aging skin in everyday practice?
Dr He: So dermatologists should be discussing lifestyle interventions that help to control inflammaging and senescence with their patients. Sun exposure, of course, pollution, environmental stress, and other components of that skin exosome all exacerbate both inflammaging and senescence. While exercise and a healthy diet reduce systemic inflammation. Diets that are high in advanced glycation end products, for example, worsen inflammaging, while Mediterranean diets, anti-inflammatory diets will all decrease systemic inflammation. So preventative and therapeutic strategies that inhibit senescence and inflammaging should be a part of the conversation that dermatologists have with patients who are concerned about skin aging.
