Introduction: What they say
A study from Department of Genetics, Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA, USA; and Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales 2052, Australia shows that “A conserved NAD+ binding pocket that regulates protein-protein interactions during aging.” This research paper was published, in the 24 March 2017 issue of the journal “Science” [One of the best research journals in Science with an I.F of 34+], by Prof. David A. Sinclair, Jun Li and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Act(os) for an enhanced, extended, and healthy lifespan: Pioglitazone (trade name: Actos), an anti-hyperglycemic agent, increases NMN/NAD levels, decreases interaction of DBC1 with PARP1, increases PARP1 activity, promotes DNA repair, augments tolerance against radiation, cancer, and aging, via down-regulation of its target gene
What is known?
Prof. David A. Sinclair’s research team has recently shown that: (a) increased levels of NAD+ (found in non-aged tissues) inhibits the interaction the between DBC1 (deleted in breast cancer 1) and PARP1 [poly(adenosine diphosphate–ribose) polymerase]; and promotes DNA repair; (b) decreased levels of NAD+ (found in aged tissues) promotes the interaction between DBC1 and PARP1 and inhibits DNA repair; (c) aged cells/tissues that are low in NAD+ are radiation-sensitive, cancer-prone and prone to accelerated ageing; and (d) ageing-associated diseases can be reversed by increasing the concentration of NAD+ in ageing tissues, suggesting that ageing-associated diseases, in part, can be reversed by NAD+ supplementation in older animals.
From research findings to therapeutic opportunity:
This study suggests, for the first time, that the anti-diabetic drug Pioglitazone–with detailed mechanistic insights–may play a role in health/lifespan. Pioglitazone, a female steroid hormone, has been shown to play a role in lifespan extension. However, the mechanistic basis of which remains largely not clear.
Pioglitazone, by increasing the expression of its target gene, it may increase the levels of NAMPT and NMN/NAD+. Thereby, it may: (1) increase plasma NMN levels and tissue NAD+ availability; (2) inhibit the interaction between DBC1 and PARP1; (3) augment PARP1’s DNA repair activity; (4) protect against radiation; (5) protect against cancer; and (6) prevent age-associated gene expression pattern and accelerated ageing(fig.1).
Thus, pharmacological formulations encompassing “Pioglitazone or its analogs, either alone or in combination with other drugs,” may be used to suppress age-associated overall physiological decline and improve health/lifespan.[easy_payment currency=”USD”]
Given the mechanistic basis of how Pioglitazone may function as an anti-aging/ longevity-promoting agent, diabetologists, gerontologists, and general practitioners may consider: treating their needy patients with pioglitazone or beginning a clinical trial.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How Pioglitazone increases the levels of NMN/NAD
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Citation: Boominathan, L., Act(os) for an enhanced, extended, and healthy lifespan: Pioglitazone (trade name: Actos), an anti-hyperglycemic agent, increases NMN/NAD levels, decreases interaction of DBC1 with PARP1, increases PARP1 activity, promotes DNA repair, augments tolerance against radiation, cancer, and aging, via down-regulation of its target gene, 29/August/2018, 8.09 am, Genome-2-Biomedicine Discovery center (GBMD), http://genomediscovery.org
Web: http://genomediscovery.org or http://newbioideas.com
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