If you removed every living cell from a human body and looked at the result, you’d still see something recognizably human: bones, of course, and the keratins that make up our skin and hair…and, forming a fine lacework throughout the entire body, the extracellular matrix (ECM). The ECM, which is a particularly prominent feature of connective tissue, consists primarily of large protein complexes that provide structural support (e.g., collagen) as well as elasticity (e.g., the appropriately named elastin).

Elastin is involved in one of the most visible consequences of aging: Over time, elastin is broken down (possibly by proteases secreted by senescent cells), and the skin becomes less resistant to mechanical force. We fight the good fight but eventually gravity wins, and we get wrinkles, wattles, and various other sorts of unmentionable sags. This is specific to later life in part because elastin is only produced during early development and childhood: What you have when you’re an adult is basically all you’ll ever have.

Elastin also has important roles inside the body, most significantly in providing the vasculature and heart with resilience and load-bearing capacity. Indeed, as reported by Pezet et al., mice that are haploinsufficient for elastin display several vascular anomalies and signs of premature cardiac aging. These animals have high blood pressure, narrow and rigid arteries, and cardiac hypertrophy even as young adults. The mice have normal lifespans, but the strain used in these studies all die of a stereotyped set of tumors at an early-to-medium age (for a mouse), so total longevity may be uninformative here.

In light of such findings, it has been suggested (as in this review by Robert et al.) that the age-related breakdown of elastin may place an upper bound on the maximum natural lifespan of the human cardiovascular system (and therefore of any human dependent on such a system).

Solution. “More elastin” sounds obvious, though one would have to be very careful: even though elastin provides elasticity, too much of it might make the arteries and heart overly rigid and unable to perform functionally necessary deformations (think about trying to blow up two nested balloons). Furthermore, excessive deposition of ECM protein in general could result in fibrosis. I would propose a two-fold approach: attack the sources of elastin degradation — calcium deposition, sun damage, and proteases secreted by senescent cells — and in the meantime, figure out how to synthesize more elastin exactly (and only) when it’s needed, so that tissue homeostasis can be preserved without untoward consequences.

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