I get this question a lot: Which is better, peptides or retinoids?  And, I should clarify that there are a lot of differences between retinoids and retinols-  but that will have to be another blog topic.  As I’m sure you’re aware, as we enter midlife, our skin’s biology changes in measurable, clinically significant ways.  Collagen production slows, elastin fibers become fragmented, cellular turnover declines, and our skin barrier weakens. Two of the most studied classes of active ingredients for addressing these changes are peptides and retinoids (including prescription tretinoin). They are often compared, but they do not function the same way and they are not mutually exclusive.

Let’s break down, scientifically, how each works and why they can (and often should) be used together.

How Retinoids Work: The Gold Standard for Cellular Turnover

Retinoids, including over-the-counter retinol and prescription tretinoin, are vitamin A derivatives that act at the nuclear receptor level. They bind to retinoic acid receptors (RARs) in keratinocytes and fibroblasts, triggering:

• Increased epidermal turnover
• Upregulation of collagen-synthesis pathways
• Reduced appearance of fine lines and photodamage
• Normalization of hyperpigmentation and dysregulated keratinization

Clinical data show that tretinoin can increase retinoid-responsive gene expression within 48 hours, and visible structural changes in collagen organization often appear within 12 weeks of sustained use.

However, retinoids can irritate our skin.  They can impair our skin’s barrier, increase TEWL, and trigger inflammation, especially in midlife when barrier lipids naturally decline.

How Peptides Work: Signaling Pathways for Firmness and Renewal

Peptides function as cell-signaling molecules, not exfoliants. The advanced peptides used in my Pentapeptide Matrix™—including Palmitoyl Tripeptide-38, Trifluoroacetyl Tripeptide-2, SH-Oligopeptide-1, Acetyl Dipeptide-1 Cetyl Ester, and Acetyl Hexapeptide-8, operate through pathways such as:

• Fibroblast stimulation to support collagen and elastin renewal
• Dermal–epidermal junction strengthening
• Enhanced skin elasticity and firmness
• Neuromodulating relaxation of expression-related lines
• Growth-factor–like effects that support healthy regeneration

Peer-reviewed data show, for example:

• Palmitoyl Tripeptide-38 boosts synthesis of six dermal matrix components, reducing wrinkle depth by 16% and volume by 31% in 60 days.
• Trifluoroacetyl Tripeptide-2 improves firmness by up to 82% and viscoelasticity by up to 42% after 28 days.
• Acetyl Hexapeptide-8 can reduce wrinkle volume by 20.6% in one week (with twice-daily application).

Peptides are non-irritating, barrier-supportive, and especially beneficial for midlife skin that needs more signaling support, not more exfoliation.

Peptides vs. Retinoids: Not an Either/Or

Retinoids drive cell turnover and gene expression, while peptides drive targeted signaling for firmness, elasticity, and repair. Their mechanisms are distinct and synergistic:

• Retinoids = renewal from the surface down
• Peptides = renewal from the inside out

For maturing skin, this combination is often ideal: retinoids enhance epidermal function; peptides support deeper structural integrity.

Can You Use Them Together? Absolutely.

At Sherak, we frequently recommend integrating tretinoin into your routine – if your skin can tolerate it and with proper barrier support. But not every woman’s midlife skin can comfortably sustain retinoid use, and it should always be personalized.

Peptides pair exceptionally well with retinoids, particularly because they strengthen the barrier, reduce irritation, and amplify firmness pathways retinoids don’t target.

And don’t forget our Barrier Shield Moisturizer can be paired safety with your retinoid.  Personally, I use tretinoin and combine this in the evening with the Barrier Shield Moisturizer.  I’ve noticed this combo gives me the benefit of the retinoid, but my skin is much more hydrated, plump and radiant than just with the retinoid alone.  

The Bottom Line for Midlife Skin

You don’t need to choose peptides or retinoids.
For most women over 40, the science supports using both:

• Retinoids for surface renewal and cell turnover
• Peptides for firmness, elasticity, lifting, and deep structural support

Together, they offer a comprehensive, biologically aligned strategy for restoring midlife skin’s resilience and radiance.