+

WO2025072329A1 - Compositions et procédés pour améliorer la durée de vie en santé - Google Patents

Compositions et procédés pour améliorer la durée de vie en santé Download PDF

Info

Publication number
WO2025072329A1
WO2025072329A1 PCT/US2024/048408 US2024048408W WO2025072329A1 WO 2025072329 A1 WO2025072329 A1 WO 2025072329A1 US 2024048408 W US2024048408 W US 2024048408W WO 2025072329 A1 WO2025072329 A1 WO 2025072329A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
composition
powder
plant materials
health
Prior art date
Application number
PCT/US2024/048408
Other languages
English (en)
Inventor
Hartley Pond
Original Assignee
DailyColors Health Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by DailyColors Health Inc. filed Critical DailyColors Health Inc.
Publication of WO2025072329A1 publication Critical patent/WO2025072329A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/742—Coffea, e.g. coffee
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger

Definitions

  • the field of the invention is compositions and methods for nutritional supplements, especially as it relates to polyphenols and polyphenol mixtures commonly associated with a diet rich in fruits and vegetables such as the Mediterranean diet, and their use in modulating health span when administered at a later stage of life.
  • compositions and methods for assisting healthy aging of a subject through administration of a combination of polyphenols and/or polyphenol-rich materials (e.g. extracts and powders) commonly found in food items of the Mediterranean diet.
  • polyphenols and/or polyphenol-rich materials e.g. extracts and powders
  • the compositions presented herein exhibited significant improvements in health span in a well-recognized animal model, improving the health span even above a potent positive control.
  • the inventor contemplates a nutritional composition for administration to a subject to assist healthy aging of the subject that includes a nutritionally acceptable carrier in combination with a plurality of chemically distinct polyphenols from plant materials having a red color, a green color, an orange-yellow color, and a purple-blue color; most preferably the composition has been demonstrated to increase locomotor activity in a C. elegans nematode in vivo model relative to a control composition not containing the plurality of chemically distinct polyphenols; additionally, it is preferred that the increase in locomotor activity is demonstrated in the latter half of lifespan of the in vivo model to thereby increase health span.
  • the red colored plant materials comprise at least one of an apple extract, a pomegranate extract, a tomato powder, and a beet root powder; wherein the green colored plant materials comprise at least one of an olive extract, a rosemary extract, a green coffee bean extract, and a kale powder; wherein the orange-yellow colored plant materials comprise at least one of an onion extract, a ginger extract, a grapefruit extract, and a carrot powder; and wherein the purple-blue colored plant materials comprise at least one of a grape extract, a blueberry extract, a currant powder, and an elderberry powder.
  • the red colored plant materials comprise at least two of an apple extract, a pomegranate extract, a tomato powder, and a beet root powder; wherein the green colored plant materials comprise at least two of an olive extract, a rosemary extract, a green coffee bean extract, and a kale powder; wherein the orange-yellow colored plant materials comprise at least two of an onion extract, a ginger extract, a grapefruit extract, and a carrot powder; and wherein the purple-blue colored plant materials comprise at least two of a grape extract, a blueberry extract, a currant powder, and an elderberry powder.
  • the red colored plant materials comprise an apple extract, a pomegranate extract, a tomato powder, and a beet root powder; wherein the green colored plant materials comprise an olive extract, a rosemary extract, a green coffee bean extract, and a kale powder; wherein the orange-yellow colored plant materials comprise an onion extract, a ginger extract, a grapefruit extract, and a carrot powder; and wherein the purple-blue colored plant materials comprise a grape extract, a blueberry extract, a currant powder, and an elderberry powder.
  • the modulation of the health span of a subject is associated with maintenance of physical and/or mental function as compared to the subject not having been administered the composition and/or improvement of physical and/or mental function as compared to the subject not having been administered the composition.
  • the health span of a subject is in respect to the group consisting of C. elegans, humans, and/or non-human mammals at a later stage in life.
  • a later stage in life comprises at least the latter third of lifespan of the in vivo model a C. elegans. or the human, or non-human mammal. .
  • the chemically distinct polyphenols are present in quantities sufficient to effect (a) modulation of health span of a subject by delaying or preventing a chronic disease; (b) modulation of health span of a subject by delaying or preventing an age- related disability; (c) modulation of health span of a subject by increasing locomotor activity; (d) modulation of health span of a subject by preserving or increasing the health of thin or thick filaments of cellular muscle fibers; (e) modulation of health span of a subject by preserving or increasing the stimulation of regions of the brain associated with reward or happiness; (f) modulation of health span of a subject by decreasing concentrations of cortisol in the nervous system; (g) modulation of health span of a subject by preserving or increasing the energy yield of metabolic processes; (h) modulation of health span of a subject by preserving or increasing the health of extracellular matrices; (i) modulation of health span of a subject by preserving or increasing intracellular NAD+ or ATP concentration; (j)
  • the delay or prevention of the chronic disease includes conditions that are a leading cause of death, that last one year or more, that require ongoing medical attention, and/or that limit daily activities of living.
  • the age-related disability includes physical and/or mental impairments that substantially limit one or more significant life activity.
  • the composition is formulated in single dosage units for oral administration (e.g., each containing between 50 and 1,500 mg of the composition), which may be formulated as a capsule, a gummy, or a powder. Where desired, the composition may further comprise an additional nutritionally acceptable functional ingredient.
  • the composition has been further demonstrated to inhibit enzymes associated with age related health decline.
  • the enzymes are ARG-1, ARG-2, SIRT1, BACE1, Cathepsin S, CDK5, IDO1, IDO2, NAMPT, PCSK9, CD47, CD38, JAK1, JAK2, JAK3, CD39, and CD73, and/or Keap/Nrf2, and/or a combination thereof.
  • the compositions presented herein will positively modulate certain pathways (and pathway elements) associated with healthy ageing.
  • the inventor additionally contemplates a method of modulating the health span of a subject which comprises orally administering to the subject the compositions presented herein. It is further contemplated that the combination of plant materials modulates the health span of a subject.
  • modulation of the health span of a subject is associated with maintenance of physical and/or mental function as compared to subject not having been administered the composition and/or improvement of physical and/or mental function as compared to subject not having been administered the composition.
  • the health span of a subject is in respect to the group consisting of C. elegans, humans, and/or non-mammals at a later stage in life.
  • a later stage in life comprises administering to a subject a combination of polyphenols from plant materials after at least 30 years of life.
  • the combination of plant materials is present in quantities sufficient to effect modulation of health span of a subject by delaying or preventing a chronic disease; modulation of health span of a subject by delaying or preventing an age-related disability; modulation of health span of a subject by increasing locomotor activity; modulation of health span of a subject by preserving or increasing the health of thin or thick filaments of cellular muscle fibers; modulation of health span of a subject by preserving or increasing the stimulation of regions of the brain associated with reward or happiness; modulation of health span of a subject by decreasing concentrations of cortisol in the nervous system; modulation of health span of a subject by preserving or increasing the energy yield of metabolic processes; modulation of health span of a subject by preserving or increasing the health of extracellular matrices; modulation of health span of a subj ect by preserving or increasing intracellular NAD+ or ATP concentration; modulation of health span of a subject by preserving or increasing the mitochondrial biogenesis; and/or modul
  • the delay or prevention of the chronic disease includes conditions that are a leading cause of death, that last one year or more, that require ongoing medical attention, and/or that limit daily activities of living.
  • the delay or prevention of the age-related disability includes physical and/or mental impairments that substantially limit one or more significant life activity.
  • the combination of plant materials is comprised of chemically distinct polyphenol-containing plant materials having a red color, a green color, an orange-yellow color, and a purple-blue color.
  • the chemically distinct polyphenol-containing plant materials having a red color comprise an apple extract, a pomegranate extract, a tomato powder, and a beet root powder; wherein the green colored plant materials comprise an olive extract, a rosemary extract, a green coffee bean extract, and a kale powder; wherein the orange-yellow colored plant materials comprise an onion extract, a ginger extract, a grapefruit extract, and a carrot powder; wherein the purple-blue colored plant materials comprise a grape extract, a blueberry extract, a currant powder, and an elderberry powder; and wherein the combination of plant materials modulates the health span of a subject.
  • the method of modulating the health span delays or prevents chronic diseases, delays or prevents age-related disabilities, preserves or increases locomotor activity, health of thin or thick filaments of cellular muscle fibers, stimulation of brain regions associated with reward or happiness, energy yield of metabolic processes, health of extracellular matrices, intracellular concentration of NAD+ or ATP, mitochondrial biogenesis, and/or glucose uptake into cells, and/or decreases concentration of cortisol in the nervous system.
  • composition is orally administered over at least 30 days with a daily dose of between 50 and 1,500 mg.
  • composition further comprises an additional nutritionally acceptable functional ingredient which is co-administered in the same dosage unit.
  • the inventor also contemplates the use of a plurality of chemically distinct polyphenols to modulate health span of a subject, wherein the chemically distinct polyphenols are present in plant materials having a red color, a green color, an orange-yellow color, and a purple-blue color, and wherein the chemically distinct polyphenols delays or prevents chronic diseases, delays or prevents age-related disabilities, preserves or increases locomotor activity, health of thin or thick filaments of cellular muscle fibers, stimulation of brain regions associated with reward or happiness, energy yield of metabolic processes, health of extracellular matrices, intracellular concentration of NAD+ or ATP, mitochondrial biogenesis, and/or glucose uptake into cells, and/or decreases concentration of cortisol in the nervous system. Therefore, the chemically distinct polyphenols are contemplated to modulate the health span of a subject.
  • the modulation of the health span of a subject is associated with maintenance of physical and/or mental function as compared to the subject not having been administered the composition and/or improvement of physical and/or mental function as compared to the subject not having been administered the composition.
  • the health span of a subject is in respect to the group consisting of C. elegans, humans, and/or non-mammals at a later stage in life.
  • a later stage in life comprises administering to a subject a combination of polyphenols from plant materials after at least 30 years of life.
  • the combination of plant materials is present in quantities sufficient to effectmodulation of health span of a subject by delaying or preventing a chronic disease; modulation of health span of a subject by delaying or preventing an age-related disability; modulation of health span of a subject by increasing locomotor activity; modulation of health span of a subject by preserving or increasing the health of thin or thick filaments of cellular muscle fibers; modulation of health span of a subject by preserving or increasing the stimulation of regions of the brain associated with reward or happiness; modulation of health span of a subject by decreasing concentrations of cortisol in the nervous system; modulation of health span of a subject by preserving or increasing the energy yield of metabolic processes; modulation of health span of a subject by preserving or increasing the health of extracellular matrices; modulation of health span of a subj ect by preserving or increasing intracellular NAD+ or ATP concentration; modulation of health span of a subject by preserving or increasing the mitochondrial biogenesis; and/or modul
  • the delay or prevention of the chronic disease includes conditions that are a leading cause of death, that last one year or more, that require ongoing medical attention, and/or that limit daily activities of living.
  • the delay or prevention of the age-related disability includes physical and/or mental impairments that substantially limit one or more significant life activity.
  • the polyphenols are provided in the form of the plant materials.
  • the red colored plant materials are selected from the group consisting of an apple extract, a pomegranate extract, a tomato powder, and a beet root powder; wherein the green colored plant materials are selected from the group consisting of an olive extract, a rosemary extract, a green coffee bean extract, and a kale powder; wherein the orange-yellow colored plant materials are selected from the group consisting of an onion extract, a ginger extract, a grapefruit extract, and a carrot powder; and wherein the purple-blue colored plant materials are selected from the group consisting of a grape extract, a blueberry extract, a currant powder, and an elderberry powder.
  • FIG.l is a graph depicting exemplary results for the fraction of C. elegans moving in response to administration of composition according to the inventive subject matter. As depicted, at 250 pg/mL, the fraction of worms moving was greater than control up to day 8, and then similar to control until the end of the assay. At 500 pg/mL, the fraction of worms moving was greater than both control and 250 pg/mL up to day 10, and then similar to control until the end of the assay.
  • the fraction of worms moving was greater than control but lower than 250 pg/mL of formulation between day 4 and day 5, then similar to 250 pg/mL from day 5 to day 9.5, and then lower than control until the end of the assay.
  • FIG.2 is a graph depicting exemplary results for mean hours C. elegans spent moving from day 4 to day 8, and from day 4 to day 13 in response to administration of composition according to the inventive subject matter, along with a positive control, sulfamethoxazole, (SMX 16 pg/mL) mean hours moving for 500 pg/mL of formulation were significantly greater than SMX, and both 250 pg/mL and 1 mg/mL formulations. For the period day 4 to day 13, the effect of 250 and 500 pg/mL and SMX were significant but not the effect of Img/mL of the formulation.
  • FIG.3 is a graph depicting exemplary results for mean speed of all C.
  • elegans in response to administration of composition according to the inventive subject matter.
  • mean speed of all worms kept declining until day 10, then plateaued until the end of the assay.
  • the mean speed of all SMX-treated worms was higher than control from day 4 to day 8.
  • mean speed of moving worms showed a dose-dependent increase, significantly higher than control and SMX treated groups.
  • FIG.4 is a graph depicting exemplary results for mean distance moved from day 4 to day 8, and from day 4 to day 13 in response to administration of composition according to the inventive subject matter. As depicted, between day 4 and day 8, the distances moved showed a statistically significant dose-response increase from control, to SMX, to 250 pg/mL formulation, to 500 pg/mL formulation. No further increase was observed from 500 pg/mL to 1 mg/mL formulations.
  • FIG.5 is a graph depicting exemplary results for the mean speed of moving C. elegans in response to administration of composition according to the inventive subject matter.
  • mean speed of moving worms showed a dose-dependent increase.
  • the mean speed of moving worms was slightly greater than the control up to day 8, but then similar to the control until the end of the assay.
  • FIG.6 is a graph depicting exemplary results for the fraction of C. elegans moving in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls.
  • the worms transferred to the formulation of the inventive subject matter on day 3 showed a significantly higher fraction of movement compared to control up to day 8, but then similar to control at the end of the assay.
  • the worms transferred to the formulation showed a higher fraction of movement compared to the positive control from day 5 to day 8, but then similar toward the end of the assay.
  • FIG.7 is a graph depicting exemplary results for the fraction of C. elegans moving in response to administration of the composition according to the inventive subject matter as compared to the negative control. Again, the worms transferred to the formulation of the inventive subject matter on day 3 showed a significantly higher fraction of movement compared to control up to day 8, but then similar to control at the end of the assay.
  • FIG.8 is a graph depicting exemplary results for the fraction of C. elegans moving in response to administration of the composition according to the inventive subject matter as compared to the positive control. Again, the worms transferred to the formulation of the inventive subject matter showed a higher fraction of movement compared to the positive control from day 5 to day 8, but then similar toward the end of the assay.
  • FIG.9 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the results for mean hours spent moving by worm in response to administration of the composition according to the inventive subject matter is significantly higher than both controls during this time period.
  • FIG.10 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the negative control. Again, the results for mean hours spent moving by worm in response to administration of the composition according to the inventive subject matter is significantly higher than control during this time period.
  • FIG.ll is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the positive control. Again, the results for mean hours spent moving by worm in response to administration of the composition according to the inventive subject matter is significantly higher than positive control during this time period.
  • FIG.ll is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the results for mean hours spent moving by worm in response to administration of the composition according to the inventive subject matter is statistically similar to the positive control, but significantly higher than control during this time period.
  • FIG.13 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.14 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • FIG.15 is a graph depicting exemplary results for mean speed of all C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the worms transferred to the formulation of the inventive subject matter showed a statistically significant increase from control and positive control from day 4 to day 8, but then similar toward the end of the assay.
  • FIG.16 is a graph depicting exemplary results for mean speed of all C. elegans in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.17 is a graph depicting exemplary results for mean speed of all C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • FIG.18 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the worms transferred to the formulation of the inventive subject matter showed a statistically significant increase in distance moved compared to both positive and negative control during this time period.
  • FIG.19 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.20 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • FIG.21 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the worms transferred to the formulation of the inventive subject matter showed a statistically significant increase in distance moved compared to both positive and negative control during this time period.
  • FIG.22 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.23 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • FIG.24 is a graph depicting exemplary results for mean speed of moving C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the worms transferred to the formulation of the inventive subject matter showed a statistically significant and consistent increase in mean speed compared to both positive and negative control.
  • FIG.25 is a graph depicting exemplary results for mean speed of moving C. elegans in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.26 is a graph depicting exemplary results for mean speed of moving C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • C. elegans Caenorhabditis elegans
  • the C. elegans in vivo model was selected especially because it shares fundamental biological mechanisms such as muscle contraction, nervous system signaling, and cell death, with humans and many other species.
  • many C. elegans genes have orthologs in humans, meaning they perform similar functions in both organisms, making it possible to study the effects of various compositions, methods, or conditions on the human gene function using C. elegans models.
  • compositions and methods disclosed herein demonstrate beneficial effects on C. elegans in vivo models, especially the increase of locomotor activity later in life, the inventors contemplate that such effects will have health span benefits on humans, non-human mammals, and non-mammals.
  • the inventors contemplate that benefits to locomotion (and other health span aspects) in C. elegans later in life have a nexus with health span benefits to humans, non-human mammals, and non-mammals, potentially later in life as well.
  • health span refers to healthy aging.
  • Health span, or healthy aging can be observed and quantified through a variety of systemic phenomena or metrics, and especially locomotor activity, which in turn is influenced by one or more underlying physiological processes or conditions that include delay and/or prevention of chronic disease, delay and/or prevention of age-related disability, health state and/or functioning of thin or thick filaments of cellular muscle fibers, stimulation of brain regions associated with reward or happiness, energy yield of metabolic processes, health state and/or functioning of thin or thick filaments of cellular muscle fibers, stimulation of brain regions associated with reward or happiness, energy yield of metabolic processes, health state and/or functioning of extracellular matrices, intracellular concentration of NAD+ or ATP, mitochondrial biogenesis, glucose uptake into cells, and concentration of cortisol in the circulatory and/or nervous system.
  • underlying physiological processes or conditions that include delay and/or prevention of chronic disease, delay and/or prevention of age-related disability, health state and/or functioning of thin or thick filaments of cellular muscle fibers, stimulation of brain regions associated with reward or happiness, energy yield of
  • Chronic disease includes conditions that are a leading cause of death as determined by the most current statistical data. For example, in the United States, as provided by the Center for Disease Control and Prevention, in 2019, some leading causes of death included heart disease, malignant neoplasms, accidents (unintentional injuries), chronic lower respiratory disease, cerebrovascular diseases, and Alzheimer disease. (National Vital Statistics Reports, Vol. 70, No. 9, Jul. 26, 2021; p.9). Chronic disease may also include a condition or disease that lasts one year or more, in either effects or treatment.
  • chronic disease Ongoing medical attention is required, from either a trained medical professional or a competent individual, for treatment of the chronic disease and/or daily activities of living are subjectively limited from the effects of said chronic disease.
  • use of chronic disease in the latter context does not necessitate that the condition or disease is also a leading cause of death.
  • the applicable definitions of the term chronic disease are not mutually exclusive to each other.
  • age-related disability includes physical and/or mental impairments that substantially limit one or more significant life activity.
  • a substantial limitation includes impairments that may be minor or major in nature but, nonetheless, have an impact on a person’s daily life such that the presence of the disability results in an increase in difficulty for completion of tasks.
  • the threshold for performing subjectively “normal” tasks decreases with age-related disability, which results in a limitation in what a person may do without increased challenge.
  • a significant life activity varies person to person but includes those activities that a person of normal health, without an age-related disability, would be able to engage in without any increased difficulty.
  • health span is to be distinguished from survivability, lifespan, and life expectancy.
  • Survivability, lifespan, and life expectancy depend upon a quantifiable amount of time that a subject may live.
  • health span depends upon the status of physiological parameters that affect a subject’s health as the subject ages. Therefore, a subject can potentially have a relatively strong survivability and long lifespan, yet have a poor health span (for example, by having weak thin and thick filaments in muscle fibers, poor glucose uptake into cells, deficient mitochondrial biogenesis, chronic disease and so on).
  • contemplated compositions and methods modulate normal locomotor activity in such a way that would not otherwise occur in untreated subjects. Such modulation was especially pronounced in the latter part of the subject’s lifespan (e.g., latter half, latter third, latter quarter, etc.), after administration at a later stage of life, which may or may not be accompanied by an increase in lifespan.
  • administration at a later stage of life is preferably provided to a subject in the latter part of the subject’s lifespan (latter half, latter third, latter quarter, etc.).
  • administration is preferably provided when the subject is at least 30 years of age, or at least 40 years of age, or at least 50 years of age, or at least 60 years of age, or at least 70 years of age, or at least 80 years of age, or at least 90 years of age, or at least 100 years of age.
  • Suitable administration ages may also be during adult years (30-39 years), or middle-aged adult years (40-59 years), or senior adult years (60+ years).
  • suitable administration for women may occur after 35% of life, 38% of life, or 50% of life, or 60% of life, or 70% of life, or 80% of life, or 90% of life, or 100% of life. Men on average live 73 years, which would result in suitable administration occurring after 35% of life, 42% of life, or 50% of life, or 60% of life, or 70% of life, or 80% of life, or 90% of life, or 100% of life.
  • contemplated compositions may also be administered when the subject is a teenager, or at least 20 years of age.
  • a nutritional composition comprises a nutritionally acceptable carrier in combination with a plurality of chemically distinct polyphenols from plant materials having a red color, a green color, an orange-yellow color, and a purple-blue color, wherein the chemically distinct polyphenols from the plant materials modulate the health span of a subject.
  • the inventor therefore also contemplates a method of modulating the health span of a subject that includes a step of orally administering to the subject the compounds and/or compositions presented herein. Most typically, the combination of plant materials modulate the health span of a subject.
  • a plurality of chemically distinct polyphenols as presented herein can be used to modulate health span of a subject.
  • the chemically distinct polyphenols are present in plant materials having a red color, a green color, an orange-yellow color, and a purple-blue color, and in especially preferred aspects, the chemically distinct polyphenols delay or prevent chronic diseases, delay or prevent age-related disabilities, preserve or increase locomotor activity, health of thin or thick filaments of cellular muscle fibers, stimulation of brain regions associated with reward or happiness, energy yield of metabolic processes, health of extracellular matrices, intracellular concentration of NAD+ or ATP, mitochondrial biogenesis, and/or glucose uptake into cells, and/or decreases concentration of cortisol in the nervous system.
  • blends of selected plant materials common in the Mediterranean diet can be prepared that modulate health span.
  • such blends are combinations of colored plant materials that belong to a number (e.g., at least two, at least three, or at least four) of different color groups, and particularly plant materials having a red color, green color, orange/yellow color, and/or purple/blue color.
  • polyphenol-containing products/extracts were obtained from red colored source materials that included an apple extract, a pomegranate extract, tomato powder, and beet root; from green colored source materials that included an olive extract, rosemary extract, green coffee bean extract, and kale; from orange/yellow colored source materials that included an onion extract, a ginger extract, a grapefruit extract, and carrot; and from purple/blue colored source materials that included a grape extract, a blueberry extract, currant, and elderberry, and the particular ingredients and proportions are described in more detail below.
  • contemplated compositions will therefore include a large number of polyphenols that below to at least two, or at least three, or at least four different polyphenolic classes, including organic acids, phenolics, flavonols, flavanols, anthocyanins, chlorogenic acids, betacyanins, etc.
  • polyphenols that below to at least two, or at least three, or at least four different polyphenolic classes, including organic acids, phenolics, flavonols, flavanols, anthocyanins, chlorogenic acids, betacyanins, etc.
  • the plant materials may be provided in various forms, including whole plant materials or portions thereof (e.g., root, fruit, leaves, etc.) in fresh or dried form, juices or macerates from plant materials or portions thereof in fresh or dried form, and aqueous or aqueous/alcoholic extracts and chromatographic fractions of the aforementioned plant materials.
  • one or more polyphenols of the plant materials may even be provided as purified (natural isolated or synthetic) chemical entities, typically with a chemical purity of at least 90%, or at least 95%, or at least 98%, or at least 99%.
  • the plant materials will be complex mixtures to provide maintenance or improvement of various aspects of prolonged health span.
  • the inventive subject matter may be formulated to meet a particular need as related to health span.
  • contemplated compositions are not limited to a single specific function (e.g., antioxidant) or limited to a specific chemical category (e.g., vitamins), but in fact complementarily and synergistically provides multiple biological activities that modulate health span.
  • contemplated compositions and methods target a variety of biological systems, including energy metabolism, immune function, neural and CNS function, cardiac function, inflammation, etc.
  • the plant materials will also provide a variety of micro-nutrients to assist or complement the functions of the polyphenols and other colored pigments present in the compositions.
  • compositions presented herein are useful to beneficially affect multiple pathways associated with health and healthy ageing via inhibition of key signaling components and/or enzymes in these pathways.
  • the observed modulation of these biomarkers using the compositions presented herein paralleled the profile of biomarkers in individuals that adhered to the Mediterranean diet and individuals with significant longevity.
  • compositions contemplated herein may be advantageously used as a stand-alone product to modulate health span such as support of proper immune function, support to reduce inflammation, support of normal NAD+ levels, support of cardiac health.
  • the term ’’support when used in conjunction with a physiological function or condition is intended to mean prevent decline of one or more components or activities of the component(s) associated with the physiological function or condition, at least partially reverse decline of one or more components or activities of the component(s) associated with the physiological function or condition, maintain normal function of one or more components or activities of the component(s) associated with the physiological function or condition, prevent abnormal overactivity (or over-expression) of one or more components associated with the physiological function or condition, and/or at least partially reverse abnormal overactivity (or over-expression) of one or more components associated with the physiological function or condition.
  • compositions contemplated herein may also be combined with other nutritional supplements and/or vitamins to provide beneficial effects otherwise not obtainable with such supplements or vitamins. It should be recognized that the compositions presented herein present a new and different class of health support with a variety of beneficial effects that reach beyond the benefits of a multivitamin formulation.
  • compositions presented herein may be formulated in a variety of forms, and particularly preferred formulations include those in combination with a nutritionally or pharmaceutically acceptable carrier, most preferably for oral administration (however, parenteral administration is also expressly contemplated). Therefore, contemplated compositions can be formulated as solid or a liquid product.
  • suitable product forms include single dosage unit formulations such as capsules, tablets, and powders, while other solid formulations include snack bars, gummies, or other edible products onto which the composition is coated (e.g., onto cereal) or into which the composition is mixed or layered (e.g., into chewing gum).
  • suitable product forms include flavored and/or carbonated beverages (e.g., tea, juice), functional beverages (e.g., sports or energy drinks) or infusions, or liquid dairy product (e.g., yoghourt, kefir).
  • flavored and/or carbonated beverages e.g., tea, juice
  • functional beverages e.g., sports or energy drinks
  • infusions e.g., yoghourt, kefir
  • liquid dairy product e.g., yoghourt, kefir
  • contemplated compositions may be provided in bulk, as part of an edible or drinkable product, and/or provided in single dosage units for consumption.
  • the daily dosage for contemplated compositions is preferably at least 10 mg, or at least 100 mg, or at least 200 mg, or at least 300 mg, or at least 400 mg, or at least 500 mg, or at least 750 mg, or at least 1,000 mg, or at least 1,500 mg, or at least 2,000 mg, or at least 2,500 mg, or at least 3,000 mg, or at least 3,500 mg, or at least 4,000 mg, but in most cases below 10,000 mg, or below 8,000 mg, or below 6,000 mg.
  • suitable dosages will be between 10-100 mg, or between 100-200 mg, or between 200-400 mg, or between 300-600 mg, or between 400-800 mg, or between 600-1,000 mg, or between 750-1,500 mg or between 750-2,000 mg, or between 1,500-2,500 mg.
  • a dosage unit will represent a recommended quantity of the compositions contemplated herein. Therefore, a dosage unit may be presented as a single item of consumption (e.g., dosage unit is a single capsule or ready-to drink beverage) or as multiple items of consumption (e.g., dosage unit distributed over 2-4 capsules). Most typically, the compositions contemplated herein will constitute at least 60%, or at least 70%, or at least 80%, or at least 85%, or at least 90%, or at least 95% of a single dosage unit given to a subject.
  • contemplated compositions may further be combined with one or more additional ingredients to impart further desirable health span modulations
  • suitable additional ingredients include vitamins (e.g., single vitamins, or vitamin blends such as multivitamin blends), dietary trace elements or minerals (e.g., individual elements or minerals, or mixtures of multiple elements or minerals in various forms), various specialty compounds and mixtures (e.g., compositions comprising nicotinamide riboside, prebiotics, human milk oligosaccharides), fatty acids, and/or one or more probiotic microorganisms (e.g., Lactobacillus spec. , Bifidobacterium spec., Leukonostoc spec., Saccharomyces boulardii, etc.).
  • vitamins e.g., single vitamins, or vitamin blends such as multivitamin blends
  • dietary trace elements or minerals e.g., individual elements or minerals, or mixtures of multiple elements or minerals in various forms
  • various specialty compounds and mixtures e.g
  • Suitable vitamins may further include one or more vitamins, and it is contemplated that the vitamins will be present in the compositions presented herein in quantities consistent with common use in the art (which may or may not exceed the FDA recommended RDA for the specific vitamin). Therefore, and among other suitable choices, preferred vitamins include vitamin A, vitamin Bl, vitamin B3 (niacin) or derivative or metabolite thereof (e.g., nicotinamide (also known as niacinamide), nicotinamide riboside, NAD), vitamin B6, vitamin B7 (biotin), vitamin B9 (folate), vitamin B12, vitamin C, vitamin D3, vitamin E, vitamin K2, and CoQlO.
  • vitamins include vitamin A, vitamin Bl, vitamin B3 (niacin) or derivative or metabolite thereof (e.g., nicotinamide (also known as niacinamide), nicotinamide riboside, NAD), vitamin B6, vitamin B7 (biotin), vitamin B9 (folate), vitamin
  • GABA 5-gamma-aminobutyric acid
  • ALA alpha lipoic acid
  • apoaequorin one or more betalains (e.g., betaxanthins or betacyanins), caffeine, carnitine, a ceramide, chondroitin and various derivatives thereof (e.g., chondroitin sulfate), a conjugated linoleic acid (CLA), creatine, curcumin, cysteine, a green tea catechin (EGCG, EC, EGC, GCG, GC), cytidine 5 -phosphocholine, dehydroepiandrosterone (DHEA), eicosapentaenoic Acid (EP A), a medium-chain fatty acid (MCFA), a short chain fatty acid (SCFA, typically between 4 and 8
  • beta sitosterol N-acetyl -carnitine, N- acetylcysteine, N-acetyltyrosine, phosphatidylserine, a phytoestrogen, a polycosanol, quercetin, resveratrol, ribose, S-adenosylmethionine (SAM), Tryptophane, tyrosine, uridine-5- monophosphate, ursolic acid, and yohimbine.
  • SAM S-adenosylmethionine
  • Contemplated elements include all micro- and macronutrients, and especially minerals and elements in complexed form (e.g., as chelate, complexed in a food matrix), covalently bound form (e.g., as organometallic compound), and in ionic form as an inorganic salt (e.g., zinc chloride), a mixed salt (e.g., zinc gluconate), or an oxide (e.g., ZmO). Therefore, and among other choices, boron, calcium, copper, iron, magnesium, molybdenum, manganese, selenium, silicon, strontium, and zinc.
  • complexed form e.g., as chelate, complexed in a food matrix
  • covalently bound form e.g., as organometallic compound
  • ionic form e.g., as an inorganic salt (e.g., zinc chloride), a mixed salt (e.g., zinc gluconate), or an oxide (e.g., Zm
  • collagen e.g., type II
  • colostrum demineralized bone matrix
  • eggshell membrane various fibers (soluble and insoluble), various beta glucans, various mushroom polysaccharides (e.g., from turkey tail, lion’s mane, shiitake, cordyceps, reishi, etc.), plant or whey protein, prebiotics (e.g., various fructooligosaccharides, xylooligosaccharides, and human milk oligosaccharides), and keratin.
  • these molecules and structures may be further processed (e.g., partial or total hydrolysis, size fractionation, etc.).
  • suitable compounds and/or extracts will include plants, plant parts (e.g, root, fruits, seed, leaves/stems, etc.), and extracts thereof, and it should be noted that the extracts may be crude pressed juices, aqueous or hydroalcoholic extracts, etc., which may be further processed to enrich in one or more desirable components using protocols well known in the art.
  • suitable plants for the compounds or extracts include Aloe vera, Ashwagandha, Bacopa monierii, Black cohosh, Boswellia, Chamomile, Chasteberry, Cissus quadrangular!
  • Especially contemplated enzymes for the compounds and/or extracts include various proteases, carbohydrate hydrolases, and lipases. Therefore, suitable enzymes include amylase, galactosidase, lactase, xylanase, bromelain, papain, and lipase. Moreover, suitable additional compounds also include pharmaceutical agents know to extend lifespan or health span such as metformin, acetylsalicylic acid, GLP-1 and GLP-1 analogs, etc.
  • probiotics suitable for use herein include bacterial and yeast probiotics.
  • suitable probiotics include various lactobacilli such as Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus gasseri, Lactobacillus plantarum, Lactobacillus paraplantarum, Lactobacillus coryniformis, Lactobacillus rhamnosus, various bifidobacterial such as Bifidobacterium lactis, Bifidobacterium breve, and Bifidobacterium longum, Leuconostoc me senter oides, Pediococcus pentosaceus, Leuconostoc citreum, Leuconostoc argentinum, Lac
  • suitable quantities may also be determined by the (preferably synergistic) effect of the compounds and/or extracts in combination with the polyphenols and polyphenol mixtures. Therefore, suitable ratios of the compounds and/or extracts to the polyphenols and polyphenol mixtures will be between 1 : 50 to 1 :20, or between 1 :20 and 1 : 10, or between 1 : 10 and 1 :5, or between 1 :5 and 1 :2, or between 1 :2 and 2: 1, or between 2 : 1 and 5 : 1 , or between 5 : 1 and 10 : 1 , or between 10:1 and 20 : 1 , or between 20 : 1 and 50.
  • compositions according to the inventive subject matter may be administered not only to a human, but also to other non-human mammals, and especially livestock and companion animals (e.g, dogs, cats, horses). Therefore, where a “subject” is described herein with respect to being administered the compositions disclosed herein, a “subject” may be a human, a mammal, a non-mammal, or C. elegans. Administration will typically be between once daily and three times daily (and in some cases even more) over a period of at least two days, three days, five days, 1 week, 2-4 weeks, 1-3 months, and even longer.
  • administration can be performed for a period sufficient to provide at least symptomatic relief of a condition (e.g., pain and swelling associated with inflammation, low energy level, frequent infections, etc.), prophylactically to avoid or help reduce severity of a health condition, and in turn modulate health span.
  • a condition e.g., pain and swelling associated with inflammation, low energy level, frequent infections, etc.
  • polyphenol-containing products/extracts common to the Mediterranean diet.
  • the polyphenolcontaining products/extracts were obtained from source materials characterized by color as follows: red group: apple extract, pomegranate extract, tomato powder, and beet root; Green group: olive extract, rosemary extract, green coffee bean extract, and kale; Orange/yellow group: onion extract, ginger extract, grapefruit extract, and carrot; and Purple/blue group: grape extract, blueberry extract, currant, and elderberry.
  • Com starch, silica, and sunflower lecithin were used as processing aids. Relative proportions are shown in Table 1 below.
  • composition was tested on the C. elegans model to investigate its effects on and ability to modulate health span in a variety of conditions.
  • the formulation (the exemplary composition) was administered on day 3 of adulthood, after the worms experience an age-related decline in mobility.
  • Age-related declines in mobility most typically occur from day 3 onwards.
  • This timeframe is also more relevant to the time of expected administration to humans, as most interventions to slow aging are targeted to adults from middle-age onwards.
  • the testing concentrations used were 250 pg/mL, 500 pg/mL and 1 mg/mL. This range of concentrations was necessary to attempt to identify the maximum efficacious concentration and/or the concentration at which the effect potentially switches from position to negative. Additionally, the duration of the assay was 14 days to allow for any longer-term effects of the formulation to be detected.
  • Assay conditions A negative (1% DMSO) control is included that is added to all petri dishes.
  • a positive control sulfamethoxazole, (SMX 16 pg/mL), a compound known to increase C. elegans lifespan (Virk et al., 2012), is also included.
  • SMX 16 pg/mL sulfamethoxazole
  • Day 3-14 For the second part of the health span assessment (Day 3-14), 3.5 cm petri dishes were poured with agar media containing a concentration series of the formulation (the exemplary composition), the solvent only control, and the SMX positive control.
  • the worms were transferred to the prepared agar plates with the different exemplary concentrations (HP 250 pg/mL, or HP 500 pg/mL, or HP Img/mL) of the composition. There is a break in the data while the worms are being transferred to the agar plates with the different conditions. Plates were then loaded onto the Wormgazer Run and started. After 14 days, the run terminated, and petri dishes were removed and inspected manually for any deviations.
  • HP 250 pg/mL or HP 500 pg/mL, or HP Img/mL
  • the fraction of worms moving was greater than both control and 250 pg/mL up to day 10, and then similar to control until the end of the assay.
  • the fraction of worms moving was greater than control but lower than 250 pg/mL of formulation between day 4 and day 5, then similar to 250 pg/mL from day 5 to day 9.5, and then lower than control until the end of the assay.
  • results Between day 4 and day 8, the mean hours moving were significantly greater for worms on all concentrations of the formulation and for SMX compared to the control. Depicted in FIG. 2, mean hours moving for 500 pg/mL of formulation were significantly greater than SMX, and both 250 pg/mL and 1 mg/mL formulations. For the period day 4 to day 13, the effect of 250 and 500 pg/mL and SMX were significant but not the effect of 1 mg/mL of the formulation.
  • Data analysis - Mean Speed The mean speed of moving worms records the average speed of only the worms that are moving at any given time point. Whereas, the mean speed of all worms records the average speed over the whole worm population, including the worms that stop moving over time. It is generated by multiplying the mean speed of moving worms by the fraction of moving worms. In worms transferred to control petri dishes on day 3, mean speed of all worms kept declining until day 10, then plateaued until the end of the assay. Depicted in FIG. 3. In worms transferred to SMX on day 3, mean speed of moving worms was similar to the control, except between day 5 to day 8, when the speed of moving SMX-treated worms was slightly higher.
  • the mean speed of all worms was greater than at 250 pg/mL up to day 6, then similar to 250 pg/mL until the end of the assay.
  • the mean speed of moving worms was greater than at 500pg/mL up to day 8, then similar to 500 pg/mL until the end of the assay.
  • the mean speed of all worms was similar to 500 pg/mL throughout the assay.
  • FIG.6 Depicted in FIG.6 is a graph showing exemplary results for the fraction of C. elegans moving in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls.
  • the worms exposed to the formulation of the inventive subject matter on day 3 showed a significantly higher fraction of movement compared to control up to day 10, and then similar to control at the end of the assay.
  • the worms exposed to the formulation showed a higher fraction of movement compared to the positive control from day 5 to day 10, and then similar toward the end of the assay.
  • FIG.7 is a graph depicting exemplary results for the fraction of C. elegans moving in response to administration of the composition according to the inventive subject matter as compared to only the negative control.
  • FIG.8 is a graph depicting exemplary results for the fraction of C. elegans moving in response to administration of the composition according to the inventive subject matter as compared to only the positive control.
  • SMX positive control standard
  • FIG.9 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As shown in FIG.9, the results for mean hours spent moving by worm in response to administration of the composition according to the inventive subject matter was significantly higher than both controls during this time period.
  • FIG.10 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to only the negative control. Again, the results for mean hours spent moving by worms in response to administration of the composition according to the inventive subject matter was significantly higher than control during this time period.
  • FIG.ll is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to only the positive control. Once more, the results for mean hours spent moving by worms in response to administration of the composition according to the inventive subject matter was significantly higher than positive control during this time period.
  • FIG.12 is a bar graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As shown, the results for mean hours spent moving by worms in response to administration of the composition according to the inventive subject matter was similar to the positive control, but significantly higher than control during this time period.
  • FIG.13 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.14 is a graph depicting exemplary results for mean hours spent moving by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive control, indicating an at least equal performance to the well-established positive control SMX.
  • FIG.15 is a graph depicting exemplary results for mean speed of all C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls.
  • the worms exposed to the formulation of the inventive subject matter showed a statistically significant increase from control and even positive control from day 4 to day 8, which then had similar performance past day 8.
  • FIG.16 is a graph depicting exemplary results for mean speed of all C. elegans in response to administration of the composition according to the inventive subject matter as compared to the negative control.
  • FIG.17 is a graph depicting exemplary results for mean speed of all C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • FIG.18 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls.
  • the worms exposed to the formulation of the inventive subject matter showed a statistically significant increase in distance moved compared to both positive and negative controls during this time period.
  • FIG.19 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 8 in response to administration of the composition according to the inventive subject matter as compared to the negative control
  • FIG.20 is a graph depicting exemplary results for mean distance moved by C.
  • FIG.21 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls.
  • FIG.21 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls.
  • the worms exposed to the formulation of the inventive subject matter showed a statistically significant increase in distance moved compared to both positive and negative control during this time period.
  • FIG.22 is a graph depicting exemplary results for mean distance moved by C.
  • FIG.23 is a graph depicting exemplary results for mean distance moved by C. elegans from day 4 to day 13 in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • FIG.24 is a graph depicting exemplary results for mean speed of moving C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive and negative controls. As depicted, the worms exposed to the formulation of the inventive subject matter showed a statistically significant increase in mean speed compared to both positive and negative control.
  • FIG.25 is a graph depicting exemplary results for mean speed of moving C. elegans in response to administration of the composition according to the inventive subject matter as compared to the negative control
  • FIG.26 is a graph depicting exemplary results for mean speed of moving C. elegans in response to administration of the composition according to the inventive subject matter as compared to the positive control.
  • compositions were effective in positively affecting multiple metrics of health span as can be seen form the changes in mean distance moved, mean speed of moving, the fraction worms moving, means hours moving, and mean speed of all worms. Further, the most significant increases in health span were observed until day 8 in the C. elegans lifespan, and sometimes until day 13 (thus extending in some cases throughout the entire lifespan).
  • the combination of the plurality of chemically distinct polyphenols from the plant materials having a red color, a green color, an orange-yellow color, and a purple-blue color may be a synergistic combination.
  • at least two of the polyphenols within one or more of the color groups may have a synergistic effect on at least one aspect of health span, or at least two color groups of the compositions as presented herein may have a synergistic effect on at least one aspect of health span.
  • administering refers to both direct and indirect administration of the pharmaceutical or nutraceutical composition, wherein direct administration of the pharmaceutical or nutraceutical composition is typically performed by a health care professional (e.g., physician, nurse, dietitian, etc.), and wherein indirect administration includes a step of providing or making available the pharmaceutical or nutraceutical composition to the health care professional or individual in need thereof for direct administration (e.g., via injection, infusion, oral delivery, topical delivery, etc.).
  • a health care professional e.g., physician, nurse, dietitian, etc.
  • indirect administration includes a step of providing or making available the pharmaceutical or nutraceutical composition to the health care professional or individual in need thereof for direct administration (e.g., via injection, infusion, oral delivery, topical delivery, etc.).
  • the terms “prognosing” or “predicting” a condition, a susceptibility for development of a disease, or a response to an intended treatment is meant to cover the act of predicting or the prediction (but not treatment or diagnosis of) the condition, susceptibility and/or response, including the rate of progression, improvement, and/or duration of the condition in a subject.
  • the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.”
  • the terms "about” and “approximately”, when referring to a specified, measurable value is meant to encompass the specified value and variations of and from the specified value, such as variations of +/-10% or less, alternatively +/-5% or less, alternatively +/-1% or less, alternatively +/-0.1% or less of and from the specified value, insofar as such variations are appropriate to perform in the disclosed embodiments.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Botany (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention présente des compositions et des procédés dans lesquels une pluralité de polyphénols chimiquement distincts module la durée de vie en santé d'un sujet lorsqu'ils sont administrés à un stade ultérieur de vie. Les compositions préférées sont formulées pour une administration orale et sont dérivées de matières végétales colorées couramment trouvées dans le régime méditerranéen.
PCT/US2024/048408 2023-09-26 2024-09-25 Compositions et procédés pour améliorer la durée de vie en santé WO2025072329A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363585503P 2023-09-26 2023-09-26
US63/585,503 2023-09-26

Publications (1)

Publication Number Publication Date
WO2025072329A1 true WO2025072329A1 (fr) 2025-04-03

Family

ID=95202071

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/048408 WO2025072329A1 (fr) 2023-09-26 2024-09-25 Compositions et procédés pour améliorer la durée de vie en santé

Country Status (1)

Country Link
WO (1) WO2025072329A1 (fr)

Similar Documents

Publication Publication Date Title
Martel et al. Antiaging effects of bioactive molecules isolated from plants and fungi
US20210008130A1 (en) Methods and compositions using bifidobacterium longum to treat or prevent depressive symptoms
CA2837751C (fr) Aliments et boissons fonctionnels ayant des proprietes synergiques pour induire l'homeostase
JP2011510684A (ja) 呼吸器状態に対する免疫反応を強化するための組成物、方法、及びキット
JP2016524614A (ja) 軟骨破壊における使用のための組成物
JP7379152B2 (ja) 筋線維化抑制用組成物
Moharreri et al. Effects of microencapsulated essential oils on growth performance and biomarkers of inflammation in broiler chickens challenged with salmonella enteritidis
US10821130B2 (en) Omega 3 fatty acids, no releasing compound and vitamin B12 as neuroprotectant in patients with no dementia
CN107530320A (zh) 肌肉脂肪化抑制用组合物
US20230346873A1 (en) Enhanced Mediterranean Diet-Based Nutritional Compositions And Methods
TW201434470A (zh) 提昇認知功能及肌肉功能之營養組合物及方法
US20130059920A1 (en) Hydroxytyrosol benefits muscle differentiation and muscle contraction and relaxation
WO2025072329A1 (fr) Compositions et procédés pour améliorer la durée de vie en santé
US20220249591A1 (en) Composition for the treatment of emotional disorders
JP2020015726A (ja) ＴＮＦ−α及びＩＬ−６産生抑制剤及びそれを用いた筋肉炎症抑制剤
JP7693243B2 (ja) 認知機能改善剤
EP3388061A1 (fr) Acides gras omega 3, composes liberant no, vitamine b12 et choline comme neuroprotecteurs pour patients sans demence
KR102796656B1 (ko) 근 감소증 개선용 혼합균주 및 이를 포함하는 조성물
AU2018238285A1 (en) Nutraceutical, dietetic and nutritional composition with antioxidant activity
CHANDRAN et al. Current Research in Nutrition and Food Science
CHANDRAN et al. Bioactive Components in Functional Foods, Mechanism of Action and Impacts on Health with a Focus on COVID-19-A Review.
Calvi HIGH-FAT DIET-INDUCED BRAIN DAMAGES: NEW NUTRACEUTICAL APPROACHES
WO2022144509A1 (fr) Composition comprenant au moins un probiotique, au moins un antioxydant et des polysaccharides de plante(s) adaptogene(s)
IT202100032279A1 (it) Vitexina o suo isomero per uso nel trattamento di ASD
DiOne AnMar Pharma

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24873489

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载