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:Molecular therapy for an enhanced, extended, and healthy lifespan: Lobeglitazone (trade name: Dovie), 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, 7/September/2018, 11.59 pm
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 Lobeglitazone–with detailed mechanistic insights–may play a role in health/lifespan.
Lobeglitazone, 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 “Lobeglitazone 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 Lobeglitazone may function as an anti-aging/ longevity-promoting agent, diabetologists, gerontologists, and general practitioners may consider: treating their needy patients with Lobeglitazone 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., Molecular therapy for an enhanced, extended, and healthy lifespan: Lobeglitazone (trade name: Dovie), 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, 7/September/2018, 11.59 pm, Genome-2-Biomedicine Discovery center (GBMD), http://genomediscovery.org
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