Circulating factors present in young mice have been shown to promote rejuvenation of aged mice, suggesting that tissues have inherent capabilities to regenerate, and circulating factors may be promoting/inhibiting this [1].

Specifically; supplementation of GDF11 (growth and differentiation factor 11) can reverse some effects of ageing (muscle tissue rejuvenates, and some degree of cognitive improvements) [2]; conversely circulating CCL11 impairs neurogenesis in aged mice and causes cognitive impairment [3]. GDF11 decreases with age, CCL11 increases with age.

from Bitto et al 2014

(Image from Bitto et al 2014, [1])

These factors (well, GDF11 at least) are not as highly expressed in humans as in mice [4], so the specific mechanisms may differ.

What other circulating factors been shown to affect health or longevity? Particularly in humans, but other mouse (or 'higher' organisms, e.g. primates) experiments would be interesting too.

  1. Bitto, A., and Kaeberlein, M., “Rejuvenation: it’s in our blood.,” Cell Metab., vol. 20, no. 1, pp. 2–4, Jul. 2014.
  2. Sinha, M., et al, “Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.,” Science, vol. 344, no. 6184, pp. 649–52, May 2014.
  3. Villeda, S., et al, “The ageing systemic milieu negatively regulates neurogenesis and cognitive function.,” Nature, vol. 477, no. 7362, pp. 90–4, Sep. 2011.
  4. Souza, T., et al, “Proteomic identification and functional validation of activins and bone morphogenetic protein 11 as candidate novel muscle mass regulators.,” Mol. Endocrinol., vol. 22, no. 12, pp. 2689–702, Dec. 2008.
  • $\begingroup$ What other circulating factors been shown to affect health or longevity? Particularly in human: The study on mice is published recently. I don't think it would have been studied in humans yet. $\endgroup$
    Commented Jan 13, 2015 at 13:06

1 Answer 1



It has been shown that oxytocin signaling helps in muscle regeneration by activating MAP Kinase/ERK pathway in skeletal muscles.[1]

Oxytocin is also known to promote adult neurogenesis.[2]


It is a paralog of GDF and like GDF prevents hypertrophy of cardiac muscles.[3]


Though leptin is not really connected to ageing but it regulates appetite and thereby the metabolism [4]. It may contribute indirectly to ageing by reducing food intake and preventing obesity and other metabolic syndromes.

This review summarizes different soluble small (synthetic) molecules that have potential to induce regeneration.

  • $\begingroup$ Thanks - did not know about oxytocin! There are other things associated with health (like IL6) but I am not sure this falls into the same category really. $\endgroup$
    – Luke
    Commented Jan 14, 2015 at 11:55
  • $\begingroup$ @Luke well ILs indicate inflammation but I am also not sure if they will fit the functional category that you are interested in. They may indirectly affect ageing process. But they don't generally affect all cells so they may be excluded. Thyroxine may also be a possible example. $\endgroup$
    Commented Jan 14, 2015 at 12:10

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