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Formulations for extending lifespan and healthspan

A technology for vitamins and compounds, applied in the field of preparations for prolonging life and health, which can solve problems such as high burden of long-term side effects

Pending Publication Date: 2020-03-24
THE BUCK INST FOR RES ON AGING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The aging patient population places an unusually high burden on drug treatments that are bioavailable, nontoxic, and lack long-term side effects

Method used

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  • Formulations for extending lifespan and healthspan
  • Formulations for extending lifespan and healthspan
  • Formulations for extending lifespan and healthspan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0277] Example 1. Screening of GRAS Compounds for Lifespan Extension in the Caenorhabditis elegans Lifespan Assay

[0278] Nematode strains and growth

[0279] Grow nematode strains under standard laboratory conditions. The nematode strains used in this study included N2, CF1038[daf-16(mu86)I], TJ1052[age-l(hx546)II], PS3551[hsf-l(sy44l)I], and TJ356[zis356 IV[daf -16::daf-16-gfp; pRF4(rol-6(sul006))]. The wild-type N2 and age-1 strains were used as negative and positive controls, respectively, while the daf-16 / hsf-1 strain was used in epistasis experiments to explore pathway involvement of lifespan-extending compounds. To explore the involvement of mTOR in compound activity without effects on development, RNAi treatment with TOR-associated genes was used (see, e.g., Sobida-Stubbs, S. et al. TOR signaling and rapamycin influence longevity by regulating SKN-1 / Nrf and DAF- 16 / FoxO. Cell Metab. 15, 713-724 (2012)).

[0280] Epistasis experiments to assess pathway involvem...

Embodiment 2

[0292] Example 2. Testing of GRAS compounds in a debilitated mouse model

[0293] animal

[0294] C57BL / 6J mice of both sexes were aged in groups in cages in an approved animal facility. Mice were maintained on a 12-h light / dark cycle with free access to food and water. Typically, interventions are initiated after mice reach 12 months of age and continue throughout the life of the mice. However, short-term or periodic intervention strategies could also be tested.

[0295] Intervention and Evaluation

[0296] Mice are randomly assigned to treatment or control groups and administered a combination of active agents or a placebo (control) in food for a sufficient duration of treatment to observe its effect on frailty characteristics.

[0297] Mice were evaluated periodically according to the 31-item clinical frailty index previously described herein. It was first reported by Whitehead et al. (Journals of Gerontology: BIOLOGICAL SCIENCES, 69:621-632; 2014). More recently,...

Embodiment 3

[0314] Example 3. Cell Senescence Test

[0315] To measure the effect of Ca-AKG on cellular senescence, IMR-90 fibroblasts in culture were gamma-irradiated after pretreatment with AKG or before Ca-AKG (post) treatment. Cellular senescence was measured by β-galactosidase fluorescence. Pretreatment of Ca-AKG protected cells from radiation-induced senescence, suggesting that one mechanism by which Ca-AKG mediates lifespan extension and frailty reduction may be by preventing cellular senescence.

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PUM

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Abstract

Described herein are compositions for delaying onset or delaying progression of frailty, reversing aging phenotype, extending healthspan, compressing morbidity, increasing lifespan and reducing formation of senescent cells.

Description

[0001] cross reference [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 489,884, filed April 25, 2017, and U.S. Provisional Application No. 62 / 646,734, filed March 22, 2018, which are hereby incorporated by reference in their entirety. Background technique [0003] The pharmacological treatment and prevention of natural aging and age-related diseases presents challenges to the medical community, partly due to the stringent properties required of agents used for this purpose. The aging patient population places an unusually high burden on drug treatments that are bioavailable, nontoxic, and lack long-term side effects. Prevention requires treatment of patients who may be at risk for age-related disorders but have no or only mild symptoms, thus requiring agents that do not compromise existing health. Treatment of patients with existing age-related diseases requires a high degree of non-toxicity that would aggravate existing medical conditions...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/194A61K31/00A61K31/07A61K31/4375
CPCA61K31/194A61K31/07A61K31/593A61K31/11A61K31/203A61K31/23A61K31/015A61K9/0053A61P39/06A61K2300/00A61K31/473A23K20/174A23K20/10A23L33/10A23L33/155A61K8/365A61K8/49A61Q5/02A61Q5/06A61Q5/10A61Q5/12A61Q7/00A61K8/67A61K8/671A61K8/675A61P17/14A61P43/00A61K9/0014A61K9/0019A23K20/126A23K20/137A61K31/37A61K31/4375A61K31/59A23K20/105A61Q5/00A61P39/00A61K31/215
Inventor 布莱恩·肯尼迪戈登·J·利思戈托马斯·韦尔登丹尼尔·埃德加马克·卢卡尼克
Owner THE BUCK INST FOR RES ON AGING
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