Rethinking Anti-Aging

For decades, skincare has centered on stimulating fibroblasts to boost collagen, promote turnover, and reverse visible aging. There is a growing realization in regenerative dermatology that chronic stimulation without adequate compensatory repair may do more harm than good. 

Emerging science shows that overactivation of growth pathways, especially the mechanistic target of rapamycin complex 1 (mTORC1),^1-5 can accelerate skin aging by exhausting the regenerative capacity of fibroblasts. Instead of supporting long-term health, overstimulation may drive cells toward senescence.

CELLULAR LONGEVITY: A FUNCTIONAL DEFINITION

Cellular longevity refers to the ability of skin cells, particularly fibroblasts, to remain functional, active, and resistant to stress over time (Figure 1). This approach aims to extend their productive lifespan—rather than excessive proliferative stimulation—which improves long-term skin resilience and appearance. 

Fig 1. Cellular longevity refers to the ability of skin cells, particularly fibroblasts, to remain functional, active, and resistant to stress over time

Clinical Advantages of the Longevity Approach

1. Preservation of native fibroblast function for firmer, healthier skin. 

2. Reduced need for replenishment from stem-cell pools, protecting regenerative reserves.

THE ROLE OF mTOR IN SKIN AGING

At the core of this new framework is the mechanistic target of rapamycin (mTOR), a nutrient-sensing pathway with 2 key complexes (Figure 2). MTORC1 promotes cell growth, protein synthesis, and metabolic activity, while MTORC2 supports survival, cytoskeletal integrity, and stress response.  

Fig 2. Mechanistic target of rapamycin (mTOR), a nutrient-sensing pathway with two key complexes.

In aging or overstimulated skin, mTORC1 becomes persistently overactive, disrupting the growth-repair cycle. This leads to mitochondrial dysfunction, oxidative stress, and a rise in senescent cells that compromise skin quality. 

THERAPEUTIC MODULATION FOR SKIN REJUVENATION 

Current research supports selectively inhibiting mTORC1 to promote autophagy and repair while preserving mTORC2 to maintain skin integrity. This dual action can clear accumulated cellular damage, restore metabolic efficiency, and delay or reverse cellular senescence. Early preclinical data in skin models show improved elasticity and reduced markers of aging when mTORC1 is modulated with precision. 

NEW THERAPEUTIC TARGET

While systemic mTOR inhibitors like rapamycin show longevity benefits, they come with drawbacks. Specifically, the non-selective inhibition of mTORC2 can impair skin barrier function. 

Next-generation topicals now aim to selectively target mTORC1 for skin-specific applications. Rapalogix Health’s RLX-201, for example, is under development to restore cellular balance without compromising barrier health or causing irritation typical of traditional stimulants. 

CLINICAL APPLICATION IN AESTHETIC DERMATOLOGY

The science of cellular longevity offers an important clinical pivot for aesthetic dermatology. Pro-longevity skincare may extend the benefits of aesthetic treatments by supporting healthier skin biology. Targeted mTOR modulation introduces a new mechanism for preventing age-related skin decline, beyond symptom management. This approach could minimize treatment fatigue and extend intervals between energy-based procedures. 

CONCLUSION

Targeting cellular longevity through selective mTOR modulation represents a promising shift in dermatologic strategy—from overstimulation to balanced rejuvenation. As evidence grows, this paradigm may redefine how practitioners approach age-related skin decline and regenerative care. 

Editor’s note: This article is based on a presentation delivered at the 2025 Genesis: Innovations in Aesthetic Regenerative Medicine meeting.

1. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274-293. doi:10.1016/j.cell.2012.03.017

2. Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature.2013;493(7432):338-345. doi:10.1038/nature11861

3. Papadopoli D, Boulay K, Kazak L, et al. mTOR as a central regulator of lifespan and aging. F1000Res. 2019;8:F1000 Faculty Rev-998. doi:10.12688/f1000research.17196.1

4. Demaria M, Ohtani N, Youssef SA, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014;31(6):722-733. doi:10.1016/j.devcel.2014.11.012 

5. Mehta RC, Day D. Selective mTORC1 inhibition as a novel pathway for skin longevity. Paper presented at: Genesis Meeting; 2025.