BPIFB4 - Revision history

Dmitry Dzhagarov: /* For further information */

2023-08-26T21:47:00Z

For further information

← Older revision		Revision as of 21:47, 26 August 2023
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	* Ciaglia, E., Lopardo, V., Montella, F., Sellitto, C., Manzo, V., De Bellis, E., ... & Puca, A. A. (2021). BPIFB4 circulating levels and its prognostic relevance in COVID-19. The Journals of Gerontology: Series A, 76(10), 1775-1783.		* Ciaglia, E., Lopardo, V., Montella, F., Sellitto, C., Manzo, V., De Bellis, E., ... & Puca, A. A. (2021). BPIFB4 circulating levels and its prognostic relevance in COVID-19. The Journals of Gerontology: Series A, 76(10), 1775-1783.
	* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294		* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294
			* Cattaneo, M., Aleksova, A., Malovini, A., Avolio, E., Thomas, A., Alvino, V. V., ... & Puca, A. A. (2023). BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice. Cell Death & Disease, 14(8), 523. PMID: 37582912 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427721/ PMC10427721] [https://doi.org/10.1038/s41419-023-06011-8 DOI: 10.1038/s41419-023-06011-8]
	[[Category:Longevity genes]]		[[Category:Longevity genes]]
	[[Category:Lifespan interventions]]		[[Category:Lifespan interventions]]
	[[Category:Main list]]		[[Category:Main list]]

Dmitry Dzhagarov: /* Molecular mechanism of LAV-BPIFB4 */

2023-02-15T21:02:57Z

Molecular mechanism of LAV-BPIFB4

← Older revision		Revision as of 21:02, 15 February 2023
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	Therapeutic effects of LAV-BPIFB4 may be due to its regulation of calcium via CXCL12 chemokine receptor CXCR4-SDF1 pathway.<ref name="”Single”" /><ref name="”SDF”" /> LAV-BPIFB4 exerted an anti-inflammatory and pro-resolving macrophage M2-polarizing effect via a CXCR4-dependent mechanism and a reduction in T-cell activation.<ref name="”Single”" /><ref name="”Huntington”">Di Pardo, A., Ciaglia, E., Cattaneo, M., Maciag, A., Montella, F., Lopardo, V., ... & Puca, A. A. (2020). The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease. Cell death & disease, 11(7), 1-16. PMID: 32683420 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858 7368858] DOI:[https://doi.org/10.1038/s41419-020-02754-w 10.1038/s41419-020-02754-w]</ref>		Therapeutic effects of LAV-BPIFB4 may be due to its regulation of calcium via CXCL12 chemokine receptor CXCR4-SDF1 pathway.<ref name="”Single”" /><ref name="”SDF”" /> LAV-BPIFB4 exerted an anti-inflammatory and pro-resolving macrophage M2-polarizing effect via a CXCR4-dependent mechanism and a reduction in T-cell activation.<ref name="”Single”" /><ref name="”Huntington”">Di Pardo, A., Ciaglia, E., Cattaneo, M., Maciag, A., Montella, F., Lopardo, V., ... & Puca, A. A. (2020). The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease. Cell death & disease, 11(7), 1-16. PMID: 32683420 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858 7368858] DOI:[https://doi.org/10.1038/s41419-020-02754-w 10.1038/s41419-020-02754-w]</ref>

	The mechanism by which LAV-BPIFB4 gene therapy supplementation restores pericyte function and pericyte-endothelial cell interactions requires the involvement of a nucleolar protein called nucleolin.<ref name="~~nucleolin~~" />		The mechanism by which LAV-BPIFB4 gene therapy supplementation restores pericyte function and pericyte-endothelial cell interactions requires the involvement of a nucleolar protein called nucleolin.<ref name="”nucleolin”"/>

	LAV-BPIFB4 activity might also be preventing the aging-specific disruption of [[NAD+]] homeostasis.<ref name="”NAD”" /> This seems to occur via the reduction of upbuilding [[CD38]]<sup>+</sup> inflammatory cells, which generally accumulate in tissues during chronological aging and actively destroy [[NAD+\|NAD<sup>+</sup>]].<ref name="”NAD”">Ciaglia, E., Lopardo, V., Montella, F., Carrizzo, A., Di Pietro, P., Malavolta, M., ... & Puca, A. A. (2022). Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline. Cell death & disease, 13(1), Article number: 86. PMID: 35087020 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792139 8792139] DOI:[https://doi.org/10.1038/s41419-022-04535-z 10.1038/s41419-022-04535-z]</ref> Long-living-individuals LAV-carriers, were characterized by having high [[NAD+\|NAD<sup>+</sup>]] levels.<ref name="”NAD”" />		LAV-BPIFB4 activity might also be preventing the aging-specific disruption of [[NAD+]] homeostasis.<ref name="”NAD”" /> This seems to occur via the reduction of upbuilding [[CD38]]<sup>+</sup> inflammatory cells, which generally accumulate in tissues during chronological aging and actively destroy [[NAD+\|NAD<sup>+</sup>]].<ref name="”NAD”">Ciaglia, E., Lopardo, V., Montella, F., Carrizzo, A., Di Pietro, P., Malavolta, M., ... & Puca, A. A. (2022). Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline. Cell death & disease, 13(1), Article number: 86. PMID: 35087020 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792139 8792139] DOI:[https://doi.org/10.1038/s41419-022-04535-z 10.1038/s41419-022-04535-z]</ref> Long-living-individuals LAV-carriers, were characterized by having high [[NAD+\|NAD<sup>+</sup>]] levels.<ref name="”NAD”" />

Dmitry Dzhagarov: /* LAV-BPIFB4 in longevity */

2023-02-15T20:56:53Z

LAV-BPIFB4 in longevity

← Older revision		Revision as of 20:56, 15 February 2023
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	Healthily aged long-living individuals have significantly higher serum BPIFB4 than do frail individuals.<ref name="”frail”"> Malavolta, M., Dato, S., Villa, F., De Rango, F., Iannone, F., Ferrario, A., ... & Puca, A. A. (2019). LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. Aging (Albany NY), 11(16), 6555. PMID: 31461407 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738439 6738439] DOI:[https://doi.org/10.18632/aging.102209 10.18632/aging.102209] </ref>		Healthily aged long-living individuals have significantly higher serum BPIFB4 than do frail individuals.<ref name="”frail”"> Malavolta, M., Dato, S., Villa, F., De Rango, F., Iannone, F., Ferrario, A., ... & Puca, A. A. (2019). LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. Aging (Albany NY), 11(16), 6555. PMID: 31461407 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738439 6738439] DOI:[https://doi.org/10.18632/aging.102209 10.18632/aging.102209] </ref>
	BPIFB4 mRNA levels are also elevated in the total circulating mononuclear cells fraction from healthy long-living individuals, as compared with non-healthy frail individuals.<ref name="”Cilento”">Spinetti, G., Sangalli, E., Specchia, C., Villa, F., Spinelli, C., Pipolo, R., ... & Puca, A. A. (2017). The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy. Aging (Albany NY), 9(2), 370. PMID: 28121621 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361669 5361669] DOI:[https://doi.org/10.18632/aging.10115 10.18632/aging.10115]</ref>		BPIFB4 mRNA levels are also elevated in the total circulating mononuclear cells fraction from healthy long-living individuals, as compared with non-healthy frail individuals.<ref name="”Cilento”">Spinetti, G., Sangalli, E., Specchia, C., Villa, F., Spinelli, C., Pipolo, R., ... & Puca, A. A. (2017). The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy. Aging (Albany NY), 9(2), 370. PMID: 28121621 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361669 5361669] DOI:[https://doi.org/10.18632/aging.10115 10.18632/aging.10115]</ref>
	Moreover, gene therapy by systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer counteracted the development of vascular atherosclerosis in ApoE knockout mice fed with a high fat diet.<ref name="”Single”">Puca, A. A., Carrizzo, A., Spinelli, C., Damato, A., Ambrosio, M., Villa, F., ... & Vecchione, C. (2020). Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. European Heart Journal, 41(26), 2487-2497. PMID: 31289820 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340354 7340354] DOI: [https://doi.org/10.1093/eurheartj/ehz459 10.1093/eurheartj/ehz459] </ref> This might make LAV-BPIFB4 a suitable candidate tool for the treatment of atherosclerosis and its related CVD complications. Furthermore, LAV-BPIFB4 gene therapy caused a temporary reduction in systolic blood pressure in diabetic and non-diabetic aged mice, with pressure values returning to baseline by day 6 until the end of the study, albeit the benefit on endothelial-mediated vasorelaxation persisted up to a month after treatment.<ref name="”SDF”">Dang, Z., Avolio, E., Thomas, A. C., Faulkner, A., Beltrami, A. P., Cervellin, C., ... & Madeddu, P. (2020). Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway. European journal of heart failure, 22(9), 1568-1581. PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220375 8220375] doi:[https://doi.org/10.1002/ejhf.1840 10.1002/ejhf.1840]</ref>
	In old mice, LAV-BPIFB4 gene transfer delayed [[frailty]] progression.<ref name="”frail”" /> Gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged (18-month-old) mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and restoration of pericyte function and pericyte-endothelial cell interactions. <ref name="~~nucleolin~~">Cattaneo, M., Beltrami, A. P., Thomas, A. C., Spinetti, G., Alvino, V., Avolio, E., ... & Madeddu, P. (2023). The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy. Cardiovascular Research. PMID: 36635236 DOI:[https:/~~/doi.org/10.1093/cvr/cvad008 10.1093/cvr/cvad008]</ref~~> "Translated to the human condition, this recovery of contractility indexes seen in older mice would correspond to rewinding the heart’s biological clock by more than 10 years."<ref>Haridy R. (2023). [https://newatlas.com/medical/unique-gene-mutation-superagers-rewind-heart-health-by-a-decade/ Unique gene mutation in superagers could rewind heart age by a decade]. New Atlas.Medical. January 23, 2023</ref>		Elderly people have a reduced exercise tolerance and a decreased left ventricle inotropic and perfusion reserve.<ref>Kokkinos, P., Faselis, C., Samuel, I. B. H., Pittaras, A., Doumas, M., Murphy, R., ... & Myers, J. (2022). Cardiorespiratory fitness and mortality risk across the spectra of age, race, and sex. Journal of the American College of Cardiology, 80(6), 598-609. PMID: 35926933 DOI: 10.1016/j.jacc.2022.05.031</ref> In addition, adrenergic responsiveness is altered with ageing. This may partly be explained by the fact that older failing hearts have a deficit in BPIFB4, which is associated with the scarcity of capillaries and surrounding pericytes.<ref name="”nucleolin”">Cattaneo, M., Beltrami, A. P., Thomas, A. C., Spinetti, G., Alvino, V., Avolio, E., ... & Madeddu, P. (2023). The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy. Cardiovascular Research. PMID: 36635236 DOI:[https://doi.org/10.1093/cvr/cvad008 10.1093/cvr/cvad008]</ref>

			''In vivo'' studies demonstrated the delivery of the LAV-BPIFB4 gene through an adeno-associated virus (AAV) carrying a liver-specific promoter exerted broad protection in rodent models of cardiovascular disease.<ref name="”nucleolin”"/> This gene transfer method allows sustained expression of secreted therapeutic proteins in the liver and systemic circulation for cross-correction of disease in other body districts.<ref name="”nucleolin”"/> In a study on elderly mice of both sexes LAV-BPIFB4 treatment reduced myocardial fibrosis and rescued cardiac function and myocardial perfusion by improving microvasculature density and pericyte coverage.<ref name="”nucleolin”"/> Moreover, gene therapy by systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer counteracted the development of vascular atherosclerosis in ApoE knockout mice fed with a high fat diet.<ref name="”Single”">Puca, A. A., Carrizzo, A., Spinelli, C., Damato, A., Ambrosio, M., Villa, F., ... & Vecchione, C. (2020). Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. European Heart Journal, 41(26), 2487-2497. PMID: 31289820 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340354 7340354] DOI: [https://doi.org/10.1093/eurheartj/ehz459 10.1093/eurheartj/ehz459] </ref> This might make LAV-BPIFB4 a suitable candidate tool for the treatment of atherosclerosis and its related CVD complications. Furthermore, LAV-BPIFB4 gene therapy caused a temporary reduction in systolic blood pressure in diabetic and non-diabetic aged mice, with pressure values returning to baseline by day 6 until the end of the study, albeit the benefit on endothelial-mediated vasorelaxation persisted up to a month after treatment.<ref name="”SDF”">Dang, Z., Avolio, E., Thomas, A. C., Faulkner, A., Beltrami, A. P., Cervellin, C., ... & Madeddu, P. (2020). Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway. European journal of heart failure, 22(9), 1568-1581. PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220375 8220375] doi:[https://doi.org/10.1002/ejhf.1840 10.1002/ejhf.1840]</ref>
			In old mice, LAV-BPIFB4 gene transfer delayed [[frailty]] progression.<ref name="”frail”" /> Gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged (18-month-old) mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and restoration of pericyte function and pericyte-endothelial cell interactions. <ref name="”nucleolin”"/> "Translated to the human condition, this recovery of contractility indexes seen in older mice would correspond to rewinding the heart’s biological clock by more than 10 years."<ref>Haridy R. (2023). [https://newatlas.com/medical/unique-gene-mutation-superagers-rewind-heart-health-by-a-decade/ Unique gene mutation in superagers could rewind heart age by a decade]. New Atlas.Medical. January 23, 2023</ref>

	==== Molecular mechanism of LAV-BPIFB4 ====		==== Molecular mechanism of LAV-BPIFB4 ====

Dmitry Dzhagarov: /* For further information */

2023-01-24T17:38:32Z

For further information

← Older revision		Revision as of 17:38, 24 January 2023
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	* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294		* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294
	[[Category:Longevity genes]]		[[Category:Longevity genes]]
			[[Category:Lifespan interventions]]
	[[Category:Main list]]		[[Category:Main list]]

Dmitry Dzhagarov: /* Molecular mechanism of LAV-BPIFB4 */

2023-01-24T17:12:30Z

Molecular mechanism of LAV-BPIFB4

← Older revision		Revision as of 17:12, 24 January 2023
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	==== Molecular mechanism of LAV-BPIFB4 ====		==== Molecular mechanism of LAV-BPIFB4 ====
	Therapeutic effects of LAV-BPIFB4 may be due to its regulation of calcium via CXCL12 chemokine receptor CXCR4-SDF1 pathway.<ref name="”Single”" /><ref name="”SDF”" /> LAV-BPIFB4 exerted an anti-inflammatory and pro-resolving macrophage M2-polarizing effect via a CXCR4-dependent mechanism and a reduction in T-cell activation.<ref name="”Single”" /><ref name="”Huntington”">Di Pardo, A., Ciaglia, E., Cattaneo, M., Maciag, A., Montella, F., Lopardo, V., ... & Puca, A. A. (2020). The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease. Cell death & disease, 11(7), 1-16. PMID: 32683420 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858 7368858] DOI:[https://doi.org/10.1038/s41419-020-02754-w 10.1038/s41419-020-02754-w]</ref>		Therapeutic effects of LAV-BPIFB4 may be due to its regulation of calcium via CXCL12 chemokine receptor CXCR4-SDF1 pathway.<ref name="”Single”" /><ref name="”SDF”" /> LAV-BPIFB4 exerted an anti-inflammatory and pro-resolving macrophage M2-polarizing effect via a CXCR4-dependent mechanism and a reduction in T-cell activation.<ref name="”Single”" /><ref name="”Huntington”">Di Pardo, A., Ciaglia, E., Cattaneo, M., Maciag, A., Montella, F., Lopardo, V., ... & Puca, A. A. (2020). The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease. Cell death & disease, 11(7), 1-16. PMID: 32683420 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858 7368858] DOI:[https://doi.org/10.1038/s41419-020-02754-w 10.1038/s41419-020-02754-w]</ref>

			The mechanism by which LAV-BPIFB4 gene therapy supplementation restores pericyte function and pericyte-endothelial cell interactions requires the involvement of a nucleolar protein called nucleolin.<ref name="nucleolin" />

	LAV-BPIFB4 activity might also be preventing the aging-specific disruption of [[NAD+]] homeostasis.<ref name="”NAD”" /> This seems to occur via the reduction of upbuilding [[CD38]]<sup>+</sup> inflammatory cells, which generally accumulate in tissues during chronological aging and actively destroy [[NAD+\|NAD<sup>+</sup>]].<ref name="”NAD”">Ciaglia, E., Lopardo, V., Montella, F., Carrizzo, A., Di Pietro, P., Malavolta, M., ... & Puca, A. A. (2022). Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline. Cell death & disease, 13(1), Article number: 86. PMID: 35087020 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792139 8792139] DOI:[https://doi.org/10.1038/s41419-022-04535-z 10.1038/s41419-022-04535-z]</ref> Long-living-individuals LAV-carriers, were characterized by having high [[NAD+\|NAD<sup>+</sup>]] levels.<ref name="”NAD”" />		LAV-BPIFB4 activity might also be preventing the aging-specific disruption of [[NAD+]] homeostasis.<ref name="”NAD”" /> This seems to occur via the reduction of upbuilding [[CD38]]<sup>+</sup> inflammatory cells, which generally accumulate in tissues during chronological aging and actively destroy [[NAD+\|NAD<sup>+</sup>]].<ref name="”NAD”">Ciaglia, E., Lopardo, V., Montella, F., Carrizzo, A., Di Pietro, P., Malavolta, M., ... & Puca, A. A. (2022). Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline. Cell death & disease, 13(1), Article number: 86. PMID: 35087020 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792139 8792139] DOI:[https://doi.org/10.1038/s41419-022-04535-z 10.1038/s41419-022-04535-z]</ref> Long-living-individuals LAV-carriers, were characterized by having high [[NAD+\|NAD<sup>+</sup>]] levels.<ref name="”NAD”" />

Dmitry Dzhagarov: /* LAV-BPIFB4 in longevity */

2023-01-24T17:01:40Z

LAV-BPIFB4 in longevity

← Older revision		Revision as of 17:01, 24 January 2023
Line 21:		Line 21:
	BPIFB4 mRNA levels are also elevated in the total circulating mononuclear cells fraction from healthy long-living individuals, as compared with non-healthy frail individuals.<ref name="”Cilento”">Spinetti, G., Sangalli, E., Specchia, C., Villa, F., Spinelli, C., Pipolo, R., ... & Puca, A. A. (2017). The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy. Aging (Albany NY), 9(2), 370. PMID: 28121621 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361669 5361669] DOI:[https://doi.org/10.18632/aging.10115 10.18632/aging.10115]</ref>		BPIFB4 mRNA levels are also elevated in the total circulating mononuclear cells fraction from healthy long-living individuals, as compared with non-healthy frail individuals.<ref name="”Cilento”">Spinetti, G., Sangalli, E., Specchia, C., Villa, F., Spinelli, C., Pipolo, R., ... & Puca, A. A. (2017). The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy. Aging (Albany NY), 9(2), 370. PMID: 28121621 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361669 5361669] DOI:[https://doi.org/10.18632/aging.10115 10.18632/aging.10115]</ref>
	Moreover, gene therapy by systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer counteracted the development of vascular atherosclerosis in ApoE knockout mice fed with a high fat diet.<ref name="”Single”">Puca, A. A., Carrizzo, A., Spinelli, C., Damato, A., Ambrosio, M., Villa, F., ... & Vecchione, C. (2020). Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. European Heart Journal, 41(26), 2487-2497. PMID: 31289820 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340354 7340354] DOI: [https://doi.org/10.1093/eurheartj/ehz459 10.1093/eurheartj/ehz459] </ref> This might make LAV-BPIFB4 a suitable candidate tool for the treatment of atherosclerosis and its related CVD complications. Furthermore, LAV-BPIFB4 gene therapy caused a temporary reduction in systolic blood pressure in diabetic and non-diabetic aged mice, with pressure values returning to baseline by day 6 until the end of the study, albeit the benefit on endothelial-mediated vasorelaxation persisted up to a month after treatment.<ref name="”SDF”">Dang, Z., Avolio, E., Thomas, A. C., Faulkner, A., Beltrami, A. P., Cervellin, C., ... & Madeddu, P. (2020). Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway. European journal of heart failure, 22(9), 1568-1581. PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220375 8220375] doi:[https://doi.org/10.1002/ejhf.1840 10.1002/ejhf.1840]</ref>		Moreover, gene therapy by systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer counteracted the development of vascular atherosclerosis in ApoE knockout mice fed with a high fat diet.<ref name="”Single”">Puca, A. A., Carrizzo, A., Spinelli, C., Damato, A., Ambrosio, M., Villa, F., ... & Vecchione, C. (2020). Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. European Heart Journal, 41(26), 2487-2497. PMID: 31289820 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340354 7340354] DOI: [https://doi.org/10.1093/eurheartj/ehz459 10.1093/eurheartj/ehz459] </ref> This might make LAV-BPIFB4 a suitable candidate tool for the treatment of atherosclerosis and its related CVD complications. Furthermore, LAV-BPIFB4 gene therapy caused a temporary reduction in systolic blood pressure in diabetic and non-diabetic aged mice, with pressure values returning to baseline by day 6 until the end of the study, albeit the benefit on endothelial-mediated vasorelaxation persisted up to a month after treatment.<ref name="”SDF”">Dang, Z., Avolio, E., Thomas, A. C., Faulkner, A., Beltrami, A. P., Cervellin, C., ... & Madeddu, P. (2020). Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway. European journal of heart failure, 22(9), 1568-1581. PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220375 8220375] doi:[https://doi.org/10.1002/ejhf.1840 10.1002/ejhf.1840]</ref>
	In old mice, LAV-BPIFB4 gene transfer delayed [[frailty]] progression.<ref name="”frail”" />		In old mice, LAV-BPIFB4 gene transfer delayed [[frailty]] progression.<ref name="”frail”" /> Gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged (18-month-old) mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and restoration of pericyte function and pericyte-endothelial cell interactions. <ref name="nucleolin">Cattaneo, M., Beltrami, A. P., Thomas, A. C., Spinetti, G., Alvino, V., Avolio, E., ... & Madeddu, P. (2023). The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy. Cardiovascular Research. PMID: 36635236 DOI:[https://doi.org/10.1093/cvr/cvad008 10.1093/cvr/cvad008]</ref> "Translated to the human condition, this recovery of contractility indexes seen in older mice would correspond to rewinding the heart’s biological clock by more than 10 years."<ref>Haridy R. (2023). [https://newatlas.com/medical/unique-gene-mutation-superagers-rewind-heart-health-by-a-decade/ Unique gene mutation in superagers could rewind heart age by a decade]. New Atlas.Medical. January 23, 2023</ref>

	==== Molecular mechanism of LAV-BPIFB4 ====		==== Molecular mechanism of LAV-BPIFB4 ====

Andrea at 11:14, 27 December 2022

2022-12-27T11:14:47Z

← Older revision		Revision as of 11:14, 27 December 2022
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	* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294		* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294
	[[Category:Longevity genes]]		[[Category:Longevity genes]]
			[[Category:Main list]]

Andrea: Edited entry

2022-12-27T10:38:22Z

Edited entry

Show changes

Dmitry Dzhagarov: /* LAV — longevity-associated variant of BPIFB4 */

2022-12-05T10:15:13Z

LAV — longevity-associated variant of BPIFB4

← Older revision		Revision as of 10:15, 5 December 2022
Line 20:		Line 20:
	BPIFB4 mRNA levels are also elevated in the total circulating mononuclear cells fraction from healthy long-living individuals as compared with non-healthy frail individuals.<ref name=”Cilento”>Spinetti, G., Sangalli, E., Specchia, C., Villa, F., Spinelli, C., Pipolo, R., ... & Puca, A. A. (2017). The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy. Aging (Albany NY), 9(2), 370. PMID: 28121621 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361669 5361669] DOI:[https://doi.org/10.18632/aging.10115 10.18632/aging.10115]</ref>		BPIFB4 mRNA levels are also elevated in the total circulating mononuclear cells fraction from healthy long-living individuals as compared with non-healthy frail individuals.<ref name=”Cilento”>Spinetti, G., Sangalli, E., Specchia, C., Villa, F., Spinelli, C., Pipolo, R., ... & Puca, A. A. (2017). The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy. Aging (Albany NY), 9(2), 370. PMID: 28121621 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361669 5361669] DOI:[https://doi.org/10.18632/aging.10115 10.18632/aging.10115]</ref>
	Moreover, gene therapy by systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer counteracted the development of vascular atherosclerosis in ApoE knockout mice fed a high fat diet, that makes LAV-BPIFB4 a suitable candidate tool for the treatment of atherosclerosis and its related CVD complications.<ref name=”Single” >Puca, A. A., Carrizzo, A., Spinelli, C., Damato, A., Ambrosio, M., Villa, F., ... & Vecchione, C. (2020). Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. European Heart Journal, 41(26), 2487-2497. PMID: 31289820 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340354 7340354] DOI: [https://doi.org/10.1093/eurheartj/ehz459 10.1093/eurheartj/ehz459] </ref> Furthermore, LAV-BPIFB4 gene therapy caused a temporary reduction in systolic blood pressure in diabetic and non-diabetic aged mice, with pressure values returning to baseline by day 6 until the end of the study, albeit the benefit on endothelial-mediated vasorelaxation persisted up to a month after treatment.<ref name=”SDF” >Dang, Z., Avolio, E., Thomas, A. C., Faulkner, A., Beltrami, A. P., Cervellin, C., ... & Madeddu, P. (2020). Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway. European journal of heart failure, 22(9), 1568-1581. PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220375 8220375] doi:[https://doi.org/10.1002/ejhf.1840 10.1002/ejhf.1840]</ref>		Moreover, gene therapy by systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer counteracted the development of vascular atherosclerosis in ApoE knockout mice fed a high fat diet, that makes LAV-BPIFB4 a suitable candidate tool for the treatment of atherosclerosis and its related CVD complications.<ref name=”Single” >Puca, A. A., Carrizzo, A., Spinelli, C., Damato, A., Ambrosio, M., Villa, F., ... & Vecchione, C. (2020). Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. European Heart Journal, 41(26), 2487-2497. PMID: 31289820 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340354 7340354] DOI: [https://doi.org/10.1093/eurheartj/ehz459 10.1093/eurheartj/ehz459] </ref> Furthermore, LAV-BPIFB4 gene therapy caused a temporary reduction in systolic blood pressure in diabetic and non-diabetic aged mice, with pressure values returning to baseline by day 6 until the end of the study, albeit the benefit on endothelial-mediated vasorelaxation persisted up to a month after treatment.<ref name=”SDF” >Dang, Z., Avolio, E., Thomas, A. C., Faulkner, A., Beltrami, A. P., Cervellin, C., ... & Madeddu, P. (2020). Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway. European journal of heart failure, 22(9), 1568-1581. PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220375 8220375] doi:[https://doi.org/10.1002/ejhf.1840 10.1002/ejhf.1840]</ref>
	In old mice LAV-BPIFB4 gene transfer delayed frailty progression.<ref name=”frail” />		In old mice LAV-BPIFB4 gene transfer delayed [[frailty]] progression.<ref name=”frail” />

	Therapeutic effects of LAV-BPIFB4 may be due to its regulation of calcium via CXCL12 chemokine receptor CXCR4-SDF1 pathway.<ref name=”Single” /><ref name=”SDF” /> LAV-BPIFB4 exerted an anti-inflammatory and pro-resolving macrophage M2-polarizing effect via CXCR4-dependent mechanism and a reduction in T-cell activation.<ref name=”Single” /><ref name=”Huntington” >Di Pardo, A., Ciaglia, E., Cattaneo, M., Maciag, A., Montella, F., Lopardo, V., ... & Puca, A. A. (2020). The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease. Cell death & disease, 11(7), 1-16. PMID: 32683420 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858 7368858] DOI:[https://doi.org/10.1038/s41419-020-02754-w 10.1038/s41419-020-02754-w]</ref>		Therapeutic effects of LAV-BPIFB4 may be due to its regulation of calcium via CXCL12 chemokine receptor CXCR4-SDF1 pathway.<ref name=”Single” /><ref name=”SDF” /> LAV-BPIFB4 exerted an anti-inflammatory and pro-resolving macrophage M2-polarizing effect via CXCR4-dependent mechanism and a reduction in T-cell activation.<ref name=”Single” /><ref name=”Huntington” >Di Pardo, A., Ciaglia, E., Cattaneo, M., Maciag, A., Montella, F., Lopardo, V., ... & Puca, A. A. (2020). The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease. Cell death & disease, 11(7), 1-16. PMID: 32683420 PMC[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368858 7368858] DOI:[https://doi.org/10.1038/s41419-020-02754-w 10.1038/s41419-020-02754-w]</ref>

Andrea: /* added to main list */

2022-11-18T15:47:10Z

added to main list

← Older revision		Revision as of 15:47, 18 November 2022
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	* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294		* Puca, A. A., Lopardo, V., Montella, F., Di Pietro, P., Cesselli, D., Rolle, I. G., ... & Ciaglia, E. (2022). The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy. Cells, 11(2), 294. https://doi.org/10.3390/cells11020294
	[[Category:Genes affecting longevity]]		[[Category:Genes affecting longevity]]
			[[Category:Longevity]]