ArticlePDF Available

Identification of Telomerase-activating Blends From Naturally Occurring Compounds

Authors:

Abstract and Figures

Context • Telomeres are repeated deoxyribonucleic acid (DNA) sequences (TTAGGG) that are located on the 5' ends of chromosomes, and they control the life span of eukaryotic cells. Compelling evidence has shown that the length of a person's life is dictated by the limited number of times that a human cell can divide. The enzyme telomerase has been shown to bind to and extend the length of telomeres. Thus, strategies for activating telomerase may help maintain telomere length and, thus, may lead to improved health during aging. Objective • The current study intended to investigate the effects of several natural compounds on telomerase activity in an established cell model of telomere shortening (ie, IMR90 cells). Design • The research team designed an in vitro study. Setting • The study was conducted at Roskamp Institute in Sarasota, FL, USA. Intervention • The tested single compounds were (1) α-lipoic acid, (1) green tea extract, (2) dimethylaminoethanol L-bitartrate (DMAE L-bitartrate), (3) N-acetyl-L-cysteine hydrochloride (HCL), (4) chlorella powder, (5) L-carnosine, (6) vitamin D3, (7) rhodiola PE 3%/1%, (8) glycine, (9) French red wine extract, (10) chia seed extract, (11) broccoli seed extract, and (12) Astragalus (TA-65). The compounds were tested singly and as blends. Outcome Measures • Telomerase activity for single compounds and blends of compounds was measured by the TeloTAGGG telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA). The 4 most potent blends were investigated for their effects on cancer-cell proliferation and for their potential effects on the cytotoxicity and antiproliferative activity of a chemotherapeutic agent, the topoisomerase I inhibitor topotecan. The benefits of 6 population doublings (PDs) were measured for the single compounds, and the 4 blends were compared to 3 concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Results • Certain of the compounds increased telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions • The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted.
Content may be subject to copyright.
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds
6 ALTERNATIVE THERAPIES, VOL. 22 NO. S2
Identication of Telomerase-activating Blends
From Naturally Occurring Compounds
Ghania Ait-Ghezala, PhD; Samira Hassan, MS; Miles Tweed, MS; Daniel Paris, PhD;
Gogce Crynen, PhD; Zuchra Zakirova, MS; Stefan Crynen, PhD; Fiona Crawford, PhD
ORIGINAL RESEARCH
ABSTRACT
Context Telomeres are repeated deoxyribonucleic acid
(DNA) sequences (TTAGGG) that are located on the
5’ ends of chromosomes, and they control the life span of
eukaryotic cells. Compelling evidence has shown that the
length of a person’s life is dictated by the limited number
of times that a human cell can divide. e enzyme
telomerase has been shown to bind to and extend the
length of telomeres. us, strategies for activating
telomerase may help maintain telomere length and, thus,
may lead to improved health during aging.
Objective • e current study intended to investigate the
eects of several natural compounds on telomerase
activity in an established cell model of telomere shortening
(ie, IMR90 cells).
Design • e research team designed an in vitro study.
Setting • e study was conducted at Roskamp Institute
in Sarasota, FL, USA.
Intervention e tested single compounds were
(1) α-lipoic acid, (1) green tea extract,
(2) dimethylaminoethanol L-bitartrate (DMAE L-bitartrate),
(3) N-acetyl-L-cysteine hydrochloride (HCL), (4) chlorella
powder, (5) L-carnosine, (6) vitamin D3, (7) rhodiola PE
3%/1%, (8) glycine, (9) French red wine extract, (10) chia
seed extract, (11) broccoli seed extract, and (12) Astragalus
(TA-65). e compounds were tested singly and as blends.
Outcome Measures Telomerase activity for single
compounds and blends of compounds was measured by the
TeloTAGGG telomerase polymerase chain reaction (PCR)
enzyme-linked immunosorbent assay (ELISA). e 4 most
potent blends were investigated for their eects on cancer-
cell proliferation and for their potential eects on the
cytotoxicity and antiproliferative activity of a
chemotherapeutic agent, the topoisomerase I inhibitor
topotecan. e benets of 6 population doublings (PDs)
were measured for the single compounds, and the 4 blends
were compared to 3 concentrations of eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA).
Results • Certain of the compounds increased telomerase
activity, and combinations of the top-ranking compounds
were able to increase telomerase activity signicantly,
from 51% to 290%, relative to controls.
Conclusions • e results have conrmed that many
naturally occurring compounds hold the potential to
activate telomerase and that certain of those compounds
have demonstrated synergistic eects to produce more
potent blends. Given the relationship between telomere
shortening, aging, and the decline of tissue function, it is
reasonable to hypothesize that such telomerase-activating
blends may have health-promoting benets, particularly
in relation to aging-associated conditions. Further
investigation of such blends in human studies that are
designed to evaluate safety and the eects on telomere
length are thus warranted. (Altern er Health Med.
2016;22(S2):6-14.)
Ghania Ait-Ghezala, PhD, is a scientist at the Roskamp
Institute, in Sarasota, Florida, and a research scientist at
James A. Haley Veterans Hospital in Tampa, Florida. Samira
Hassan, MS, is a research assistant; Miles Tweed, MS, is a
research assistant; and Stefan Crynen, PhD, is a scientist at
the Roskamp Institute. Daniel Paris, PhD, is a scientist at
the Roskamp Institute and a research scientist at James A.
Haley Veterans Hospital. Gogce Crynen, PhD, is a scientist
at the Roskamp Institute and a research scientist at the
Open University, Milton Keynes. Zuchra Zakirova, MS, is a
research assistant at the Roskamp Institute and a research
assistant at James A. Haley Veterans Hospital. Fiona
Crawford, PhD, is president and CEO of the Roskamp
Institute and a VA research career scientist at James A.
Haley Veterans Hospital.
Corresponding author: Ghania Ait-Ghezala, PhD
E-mail address: gaitghezala@rfdn.org
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds ALTERNATIVE THERAPIES, VOL. 22 NO. S2 7
Telomeres are repeated deoxyribonucleic acid (DNA)
sequences (TTAGGG) located on the 5’ ends of
human chromosomes. e length of the telomere in
human somatic cells is believed to be heterogeneous, ranging
from 5 to 20 kb and is determined by a person’s age, the organ
examined, and the number of divisions that each of its cells
has endured.1
A telomere can lose up to 200 bases with each DNA
replication cycle. e progressive shortening of telomeres that
follows is one of the molecular mechanisms associated with aging,
because critically short telomeres trigger chromosome senescence
and loss of cell viability.1-3 Telomere shortening occurs as a result
of the progressive loss of these repeated nucleotide sequences that
takes place over many replication cycles. at loss can be stopped
and even reversed by the enzyme telomerase.4,5
Telomerase is a ribonucleoprotein enzyme that lengthens
the telomere by extending the DNA termini. Telomere length
has also been found to decrease with age in humans, suggesting
a role between telomere length and the fate of cells and the
decline of tissue function that eventually aects mortality.6
It h as been suggested that sh elter in, a protein complex
with DNA remodeling activity, acts together with several
associated DNA-repair factors to fold the telomeres end into a
properly capped structure, thereby protecting chromosomes
ends.7 It is also known that cellular senescence can be triggered
by the accumulation of too many uncapped telomeres and that
the repair of critically short telomeres by telomerase or
recombination is limited in most somatic cells. erefore, the
length of the telomere repeats can regulate the proper capping
of the ends of the chromosomes and protect them.
Telomerase aects longevity by preventing premature
telomere erosion, with that loss exemplied by human
diseases with mutations in telomerase components.
Individuals with such mutations oen develop premature
dysfunction of adult stem cells and show signs of decreased
longevity due to accelerated rates of telomere shortening.2,8-12
Although no evidence is available that telomerase drives
the oncogenic process, it is permissive and required for the
sustained growth of cancers. erefore, almost all human
cancers show telomerase activation as a hallmark process, and
it is the likely mechanism that allows unlimited cell proliferation
of tumor cells.13 However, telomere erosion has also been
documented in hyperproliferative disease states, as a condition
strongly associated with increased cancer risk. Short telomeres
have a higher predisposition to induce chromosome
rearrangements that can lead to cancer, and it has been
suggested that short telomeres may actually be a cause of
cancer14,15 and may precede reactivation of telomerase.5,16,17
Two studies have suggested that the activation of
telomerase is sucient to delay aging and increase the
lifespan in normal aging and accelerated aging mice, without
any increase in cancer incidence.18-20 Many more studies have
suggested that the reactivation of telomerase in adult or aged
organisms has a similar positive eect on the delay of aging
and that the mechanism may be independent of its role in
cancer proliferation where it is aberrantly expressed.
Given the projected increase in life span of the human
population, healthy aging might be facilitated by approaches
that maintain telomere length. A few compounds are already
commercially available, in the form of dietary supplements,
that claim to maintain or repair telomere length and that are
associated with increased longevity through telomerase
activation.18
e present study was designed to investigate the eects
of a variety of natural compounds on telomerase activity,
followed by an evaluation of whether combinations of the
most potent telomerase modulators might enhance the
performance of any single modulator. Also, given the tight link
between telomerase activity, cellular senescence, and cancer,
the eects of the 4 most eective blends for the increase of
telomerase activity were investigated regarding their eects on
tumor cell proliferation and survival in response to a
chemotherapeutic agent, to assess any potential cancer risk
associated with their promotion of telomerase activity.
METHODS
e eects of the current study’s compounds and their
combinations on telomerase activity were tested in vitro using
primary human IMR90 cells. e cells were treated with each
compound for 15 population doublings (PDs) and compared
to the commercially available telomerase activator, Astragalus
(TA-65), which has been shown to have benecial eects by
increasing telomerase activity.18,21-23 e 4 blends that showed
the highest performance were also compared in the same assay
to the eects of omega-3 fatty acids (FAs), which have been
shown to increase telomere length in a human study.24
Cells
e telomeres of IMR90 cells shorten by an average of
70 base pairs per division.25 ose cells were chosen for the
current study. IMR90 cells were purchased from ATCC
(Rockville, MD, USA) and the cells were grown in Eagle’s
minimum essential medium (EMEM) from the American
Type Culture Collection (ATCC) (Manassas, VA, USA),
supplemented with 10% fetal bovine serum in a 5% CO2,
humidied environment at 37°C.
Procedures
Single Compounds. e tested compounds were
(1) α-lipoic acid, (1) green tea extract, (2) dimethylaminoethanol
L-bitartrate (DMAE L-bitartrate), (3) N-acetyl-L-cysteine
hydrochloride (HCL), (4) Chlorella powder, (5) L-carnosine,
(6) vitamin D3, (7) rhodiola PE 3%/1%, (8) glycine,
(9) French red wine extract, (10) chia seed extract,
(11) broccoli seed extract, (12) Astragalus extract, and
(13) TA-65, which acted as the positive control. TA-65 has
been previously described as a compound capable of
increasing average telomere length by turning on the hTERT
gene, which activates telomerase.
All of the compounds tested were provided by
Enzymedica (Venice, FL, USA). Eicosapentaenoic acid
(EPA)—20:5, n-3; docosahexaenoic acid (DHA)—22:6, n-3;
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds
8 ALTERNATIVE THERAPIES, VOL. 22 NO. S2
and delipidated and charcoal-treated fetal bovine serum were
all purchased from Sigma-Aldrich (St Louis, MO, USA).
Blends of Compounds. Eight compounds were tested:
(1) BL-1: rhodiola PE 3%/1%, sulforaphane glucosinolate
(SGS) broccoli seed extract, Astragalus extract, L- carnosine,
N-acetyl-L-cysteine HCL, and vitamin D3; (2) BL-2: rhodiola
PE 3%/1%, SGS broccoli seed extract, Astragalus extract,
L-carnosine, N-acetyl-L-cysteine HCL, vitamin D3, and an
enzyme blend containing xylanase, pectinase, hemicellulase,
cellulase TB, protease, and catalase; (3) BL-3: Astragalus
extract, SGS broccoli seed extract, rhodiola PE 3%/1%, and
vitamin D3; (4) BL-4: Astragalus extract, SGS broccoli seed
extract, and rhodiola PE 3%/1%; (5) BL-5: Chlorella powder,
Astragalus extract , rhodiola PE 3%/1%, N-acetyl-L-cysteine
HCL, SGS broccoli seed extract, L-carnosine, and vitamin D3;
(6) BL-6: rhodiola PE 3%/1%, N-acetyl-L-cysteine HCL,
L-carnosine, SGS broccoli seed extract, and vitamin D3;
(7) BL-7: Chlorella powder, glycine, and vitamin D3; and
(8) BL-8: rhodiola PE 3%/1%, L-carnosine, SGS broccoli seed
extract, L-carnosine, Chlorella powder, and TA-65.
Enzymedica currently markets BL-3 as Telomere Plus.
Lactate Dehydrogenase Assay. Regarding the cell
treatments and sample collection, all compounds were rst
tested for their toxicity by measuring the release of lactate
dehydrogenase (LDH) from Roche (Indianapolis, IN, USA) at a
dose range of 50 μg/mL to 1000 µg/mL. e cells were then
treated with each compound for 15 PDs, unless stated otherwise.
Overall, the cells were passaged into several asks and allowed
to attach for a few hours, before subsequently being treated for
72 hours with the test compound. Aer the 72 hours, the cells
were detached with TrypLE (Invitrogen, Grand Island, NY,
USA). Half of the cells were washed and ash frozen in a -80°C
freezer for analyses, and the other half were seeded in a fresh
ask and treated with the same compound for 72 hours. e
same paradigm was repeated for up to 15 PDs.
Sample Preparation. Aer the last PD treatment and
sample collection (PD-15), cells from all passages, including
previously frozen passages, were resuspended in a 150-L lysis
reagent provided in the telomeric repeat amplication protocol
(TRAP) assay, precooled on ice, and incubated for 30 minutes
on ice. e samples were prepared as per the manufacturer’s
recommendation; briey, cell lysates were centrifuged at
16
000
×
G for 20 minutes at 2°C to 8°C. e supernatant was
carefully collected, and the protein content was subsequently
quantied using a bicinchoninic acid (BCA) assay.
Outcome Measures
TRAP Assay. e telomerase activity was measured by a
TeloTAGGG telomerase polymerase chain reaction (PCR)
enzyme-linked immunosorbent assay (ELISA) assay from
Roche. It is a photometric enzyme immunoassay that is used
for the detection of telomerase activity using TRAP. e
procedure was performed in accordance with the
manufacturer’s instructions. Briey, a rst-step PCR elongation
and amplication was followed by an ELISA detection step.
For each reaction, the negative control was a heat-treated
sample, and the positive control was a human embryonic
kidney (HEK) cell extract that was provided in the kit.
Cytotoxicity and Cell Proliferation Screening. e
4 blends that were found to be most potent for telomerase
activity—BL-1, BL-2, BL-3, and BL-4—were also investigated for
their eects on cancer cell proliferation. Adenocarcinomic,
human, alveolar basal epithelial cells (A549 cells) were grown in
Dulbeccos modied Eagle medium (DMEM) from ermoFisher
Scientic (Grand Island, NY, USA), which was supplemented
with 10% fetal bovine serum and 1× penicillin/streptomycin. In
addition, the potential impacts of BL-1, BL-2, BL-3, and BL-4 on
the cytotoxicity and the antiproliferative activity of a
chemotherapeutic agent, the topoisomerase I inhibitor topotecan,
was investigated at a dose range of 0.1 μM to 10 μM of topotecan.
Cytotoxicity was monitored by measuring the release of
LDH in the culture media, following 48 hours of treatment
with a dose range of topotecan. In addition, the number of
live cells adherent to the cell culture wells was quantied by
measuring the cleavage of the tetrazolium salt WST-1 to
formazan by cellular mitochondrial dehydrogenases
(Biovision, Milpitas, CA, USA), to determine the eect of the
dierent treatments on cellular proliferation.
Preparation of Albumin-bound FAs. Cultured IMR90
cells were incubated with albumin-bound EPA—20:5, n-3;
sigma or DHA—22:6, n-3; sigma, for 72 hours in EMEM
containing 10% delipidated and charcoal-treated, fetal bovine
serum to minimize interference from serum FAs and to
obtain a better-dened system.
Briey, the EPA and DHA were resuspended in ethanol
and stored at -20°C under nitrogen. e concentrations of
DHA and EPA to be tested were evaporated to dryness under
reduced pressure and the FAs were complexed with the
depleted bovine serum albumin in a 1:1 molar ratio according
to the method described by Mahoney.26 e n a l c o n ce n t ra t i on s
were EPA 25 μM/DHA 2.5 μM; EPA 2.5 μM/DHA 0.25 μM;
and EPA 0.25 μM/DHA 0.025 μM. e treatment was carried
out for 6 PDs and compared with the 4 most potent blends,
BL-1, BL-2, BL-3, and BL-4.
Statistical Analysis
A matched-pairs t test was used to assess signicant
changes between 2 time points. Statistical signicance was
set at α
<
.05 for all statistical analyses. Statistical signicance
is indicated with a notation in graphs.
RESULTS
LDH Assay
e results revealed that 24 hours of treatment with
200 μg/mL of DMAE L-bitartrate, N-acetyl-L-cysteine HCL,
Chlorella powder, or L-carnosine did not show any toxicity;
thus, that dose was selected for those 4 compounds.
e TA-65, vitamin D3, α-lipoic acid, green tea extract, and
rhodiola PE 3%/1% were toxic at doses higher than 50 μg/mL;
therefore, that concentration was used for those compounds.
In addition, the French wine extract showed some
toxicity at a dose of 500 μg/mL, and Astragalus extract
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds ALTERNATIVE THERAPIES, VOL. 22 NO. S2 9
showed toxicity at a dose of 1000 μg/mL;
therefore, those 2 compounds were tested at
250 μg/mL and 750 μg/mL, respectively.
Glycine, chia seed extract, and broccoli seed
extract did not show any toxicity at the highest
dose tested, 1000 μg/mL, aer 24 hours of
treatment; therefore, those compounds were
subsequently tested at 1000 μg/mL.
e chia seed and Astragalus extract were
poorly soluble and, therefore, the powder was
crushed using a pestle and mortar, and
subsequently resuspended in ethanol and
dimethyl sulfoxide (DMSO), respectively,
before nally being sonicated for 1 minute. e
soluble fraction was collected and then ltered
via a 0.22 μm lter before use. erefore,
although the starting dose of the powder was
50 μg/mL, some of the powder remained
undissolved; thus, the nal dose was an estimate
(data not shown).
Single Compounds
To investigate the telomerase activity in the
single compounds, the research team selected
passages 2, 8 or 10, and 15 to compare the
telomerase activity prole. e data showed that
telomerase activity was reduced with time in the
control cells that were not treated, with P
=
.045
when comparing PD-2 to PD-8 and P
=
.012 when
comparing PD-2 to PD-15 (Figure 1). at nding
was as the research team expected, reecting a
shortening of the telomeres of the primary IMR90
cells because those cells have a nite life span.
e telomerase assay detected a signicant
increase in the telomerase activity for the positive
control, TA-65, with P
=
.0023 and P
=
.007 when
comparing PD-2 to PD-8 and PD-2 to PD-15,
respectively (Figure 1).
Compounds Showing Evidence for
Increasing Telomerase Activity. When
comparing PD-2 to PD-8 for L-carnosine,
N-acetyl-L-cysteine, and DMAE L-bitartrate, no
signicant dierences were detected. However,
when comparing PD-2 to PD-15, those
2 compounds, a signicant increase in telomerase
activity was observed, with P
=
.005 and P
=
.007,
respectively (Figure 1). No trend existed for
DMAE L-bitartrate to increase telomerase
activity when comparing PD-2 to PD-15, and
that measure did not reach statistical signicance,
with P
=
.089 (Figure 1).
Tre at me nt w it h vi ta mi n D 3 showed
signicantly increased telomerase activity when
comparing PD-2 to PD-8, with P
=
.036, and a
marginally signicant increase when comparing
PD-2 to PD-15, with P
=
.047 (Figure 2).
Figure 1. Mean Value of Telomerase Activity With Time at PD-8 and
PD-15 Compared With PD-2, for α-Lipoic Acid, Green Tea Extract,
DMAE L-bitartrate, N-acetyl-L-cysteine HCL, Chlorella Powder, TA-65,
and L-Carnosine
Note: Each error bar was constructed using 1 standard error from the
mean. Statistical signicance was set at α
=
.05 for all statistical analyses.
aFor L-carnosine, P
=
.005 and for N-acetyl-L-cysteine HCL, P
=
.007 for
PD-2 to PD-15, both signicant increases. For TA-65, P
=
.0023 and
P
=
.007, for PD-2 to PD-8 and for PD-2 to PD-15, respectively, both
signicant increases. For α-lipoic acid, P
=
.042 for PD-2 to PD-8 and
P
=
.021 for PD-8 to PD-15, both signicant decreases. For green tea
extract, P
=
.023 for PD-2 to PD-15, a signicant decrease.
Abbreviations: DMAE, dimethylaminoethanol; HCL, hydrochloride.
Figure 2. Mean Value of Telomerase Activity With Time at PD-8 and
PD-15 Compared With PD-2 for Vitamin D3 and Rhodiola PE 3%/1%
Note: Each error bar was constructed using 1 standard error from the
mean. Statistical signicance was set at α
=
.05 for all statistical analyses.
aFor vitamin D3, P
=
.036 for PD-2 to PD-8 and P
=
.047 for PD-2 to PD-15,
both signicant increases. For rhodiola PE 3%/1%, P
=
.066 for PD-2 to
PD-15, an increase indicating a trend toward signicance.
Telomerase Activity % of PD-2
350
300
250
200
150
100
50
0
Control
Green Tea Extract
α-Lipoic Acid
Chlorella Powder
DMAE L-Bitartrate
N-acetyl-L-Carnosine
L-Carnosine
TA-65
a
a
a
a
a
aa
a
a
PD-2
PD-8
PD-15
PD-2
PD-8
PD-15
ControlVitamin D3Rhodiola
PE 3%/1%
a
a
a
250
200
150
100
50
0
Telomerase Activity % of PD-2
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds
10 ALTERNATIVE THERAPIES, VOL. 22 NO. S2
e rhodiola PE 3%/1% treatment showed a trend toward
an increase in telomerase activity but only for the comparison
of PD-2 to PD-15, with P
=
.066. No signicant change was
detected when comparing PD-2 to PD-8 (Figure 2).
In addition, the results from the telomerase assay
detected a signicant increase in telomerase activity with the
Astragalus extract treatment, with P
=
.0068 when comparing
PD-2 to PD-10 and P
=
.0014 when comparing PD-2 to
PD-15 (Figure 3). When comparing PD-2 to PD-10 for the
broccoli seed extract, no signicant dierences were detected;
however, when comparing P-2 to P-15, a signicant increase
in telomerase activity was observed, with P
=
.018 (Figure 3).
e chia seed extract showed a marginally signicant
increase in telomerase activity, with P
=
.048 when comparing
PD-2 to PD-10, but that eect was lost when comparing
PD-2 to PD-15, with P
=
.07 (Figure 3).
Compounds Showing Evidence for Stabilizing
Telomerase Activity. Chlorella powder did not have any
eect on telomerase activity but also did not show any
evidence of telomere shortening, suggesting that the Chlorella
powder maintained the same level of telomerase activity with
time (Figure 1). A similar eect was seen with the glycine
treatment, suggesting a stabilization of telomerase activity
with time (Figure 3).
Figure 3. Mean Value of Telomerase Activity With Time at
PD-10 and PD-15 Compared With PD-2 for Glycine, French
Wine Extract, Chia Seed Extract, Astragalus Extract, and
Broccoli Seed Extract
Note: Each error bar was constructed using 1 standard error
from the mean. Statistical signicance was set at α
=
.05 for all
statistical analyses.
aFor Astragalus, P
=
.0068 for PD-2 to PD-10 and P
=
.0014 for
PD-2 to PD-15, both signicant increases. For broccoli seed
extract, P
=
.018 for PD-2 to PD-15, a signicant increase.
For chia seed extract, P
=
.048 for PD-2 to PD-10, a
marginally signicant increase, but the eect was lost when
comparing PD-2 with PD-15, with P
=
.07. For French wine
extract, P = .021 for PD-2 to PD-10 and P
=
.003 for PD-2 to
PD-15, both signicant decreases.
Telomerase Activity % of PD-2
200
180
160
140
120
100
80
60
40
20
0
Glycine
Chia Seeds
French Wine
Astragalus
Broccoli Seeds
Control
a
PD-2
PD-8
PD-15
a
aa
a
a
a
Figure 4. Eect of Blends BL-1 to BL-8 on Telomerase
Activity: Mean Value With Time at PD-8 and PD-15
Compared With PD-2
Note: Each error bar was constructed using 1 standard
deviation from the mean. Statistical signicance was set at
α
=
.05 for all statistical analyses.
aFor BL-1, P
=
.022 for PD-2 to PD-8 and P
=
.044 for PD-2 to
PD-15, both signicant increases. For BL-2, P
=
.019 for
PD-2 to PD-8 and P
=
.002 for PD-2 to PD-15, both
signicant increases. For BL-3, P
=
.041 for PD-2 to PD-8
and P
=
.011 for PD-2 to PD-15, both signicant increases.
For BL-4, P
=
.034 for PD-2 to PD-8 and P
=
.011 for PD-2 to
PD-15, both signicant increases. For BL-8, P
=
.028, a
signicant increase for PD-2 to PD-8 only. For BL-5,
P
=
.016 for PD-2 to PD-15, a signicant increase. For BL-6,
P
=
.016 for PD-2 to PD-15, a signicant increase. For BL-7,
P
=
.013 for PD-2 to PD-15, a signicant increase.
Compounds Showing Evidence for Decreasing
Telomerase Activity. Cells treated with α-lipoic acid showed
a similar prole to the control sample, denoting reduced
telomerase activity and, therefore, shorter telomeres. A
signicant decrease in telomerase activity appeared for that
compound when comparing PD-2 to PD-8 and PD-2 to
PD-15, with P
=
.042 and P
=
.021, respectively (Figure 1).
Green tea treatment did not show any eect on
telomerase activity from PD-2 to PD-8, but from PD-2 and
PD-15, a clear reduction in telomerase activity occurred,
with P
=
.023 (Figure 1). Similarly, treatment with French
wine extract revealed a clear decrease in telomerase activity
when comparing PD-2 to PD-10 and PD-2 to PD-15, with
P
=
.021 and P
=
.003, respectively (Figure 3).
Blends of Compounds
Aer the initial screening with the individual compounds,
the research team tested 8 proprietary blends (BL-1 through
BL-8) from the best performing compounds. e results from
the telomerase assay detected a signicant increase in
telomerase activity with the BL-1 blend when comparing PD-2
Telomerase Activity % of PD-2
450
400
350
300
250
200
150
100
50
0
Control
PD-2
PD-8
PD-15
BL-1
BL-2
BL-3
BL-4
BL-5
BL-6
BL-7
BL-8
a
a
a
a
a
a
a
a
a
a
a
a
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds ALTERNATIVE THERAPIES, VOL. 22 NO. S2 11
to PD-8 and PD-2 to PD-15, with P
=
.022 and P
=
.044,
respectively (Figure 4). A similar trend was found for blends
BL-2, BL-3, and BL-4 when comparing PD-2 to PD-8 and
PD-15, with P
=
.019 and P
=
.002, respectively, for BL-2;
P
=
.041 and P
=
.011, respectively, for BL-3; and P
=
.034 and
P
=
.011, respectively, for BL-4. (Figure 4).
Upon examining BL-8, statistical signicance was
reached only when comparing PD-2 to PD-8, with P
=
.028.
No statistical signicance was observed when comparing
PD-2 to PD-15 (Figure 4). In addition, upon comparing
PD-2 to PD-8 for the BL-5 and BL-6 blends, a trend toward
an increase in telomerase activity was observed. Finally,
statistically signicant dierences were observed for all
3 blends—BL-5, BL-6, and BL-7—when comparing PD-2 to
PD-15, with P
=
.016, P
=
.016, and P
=
.013, respectively
(Figure 4). e data also show that telomerase activity was
reduced with time in the control cells, which were not
treated, when comparing PD-2 to PD-15, with P
=
.08, but the
measure did not reach statistical signicance (Figure 4).
Overall, the data suggested that some blends—BL-1,
BL-2, BL-3, and BL-4—outperformed the other blends. e
blends BL-5, BL-7, and BL-8 were the least ecient at
increasing telomerase activity. BL-6 showed a similar
telomerase activity to the BL-5, BL-7, and BL-8 (Figure 4).
BL-1, BL-2, BL-3, and BL-4 were compared to treatment
with omega-3 FAs, which had previously been shown to
increase telomere length, with decreasing n-6:n-3 omega-3
polyunsaturated fatty acid (PUFA) ratios in a human, double-
blind, 4-month, randomized, controlled trial.26 Because the
current study’s data indicated signicant eects for those rst
4 blends by PD-5, the comparison to omega-3 FAs was
stopped at PD-6 for evaluation of telomerase activity against
PD-1. Overall, the results indicated that the blends
outperformed all of the DHA/EPA doses tested.
e current study’s data showed that the telomerase
activity was reduced with time in the control cells when
comparing P-1 with P-6, with P
=
.044 (Figure 5).
A comparison of the eects of various EPA/DHA doses also
showed that statistical signicance was reached only when
comparing P1 with P6 for the omega-3 dose combination of
EPA 2.5M/DHA 0.25M, with P
=
.024 (Figure 5). No statistical
signicance was observed when comparing other passages,
nor were any dierences observed with the other dose
combinations omega-3 FAs that were tested.
However, a signicant increase in telomerase activity was
detected with BL-2 when comparing PD-1 to PD-4 and PD-1 to
PD-6, with P
=
.032 and P
=
.047, respectively (Figure 5). A
similar trend was found for BL-3 when comparing P-1 to P-2
and P-2 to P-6, with P
=
.024 and P
=
.021, respectively, and for
blend BL-4, when comparing P-2 to P-6 with P
=
.023 (Figure 5).
A trend toward an increase in telomerase activity was
observed when comparing PD-1 and the subsequent passages
of the BL-1 blend (Figure 5); however, no statistical
signicance was reached.
Figure 5. Mean Value of Telomerase Activity With Time at PD-2, PD-8, and PD-15 Compared With PD- 1, for the Best
4 Blends Compared With EPA/DHA
Note: Each error bar was constructed using 1 standard deviation from the mean. Statistical signicance was set at
α
=
.05 for all statistical analyses.
aFor BL-2, P
=
.032 for PD-1 to PD-6 and P
=
.047 for PD-4 to PD-6, both signicant increases. For BL-3, P
=
.024 for PD-1 to
PD-2 and P
=
.021 for PD-2 to PD-6, both signicant increases. For BL-4, P
=
.023 for PD-2 to PD-6, a signicant increase.
Abbreviations: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.
Telomerase Activity % of PD-1
250
200
150
100
50
0
Control
BL-1
BL-2
BL-3
BL-4
EPA 25 μM/DHA 2.5 μM
PD-1
PD-2
PD-3
PD-4
EPA 2.5 μM/DHA 0.25 μM
EPA 0.25 μM/DHA 0.025 μM
a
a
a
a
a
a
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds
12 ALTERNATIVE THERAPIES, VOL. 22 NO. S2
Eects of the 4 Most Potent Blends on Tumor Cell
Proliferation and Survival. No eects occurred for BL-1,
BL-2, BL-3, or BL-4 on viability or proliferation of the A549
cells following 48 hours of treatment (data not shown). In
addition, the potential eects of BL-1, BL-2, BL-3, and BL-4
on the cytotoxicity and the antiproliferative activity of the
chemotherapeutic agent topotecan were further investigated.
e research team found that BL-1, BL-2, BL-3, and BL-4
(Figures 6 and 7) did not aect topotecan’s anticancerous
activity in A549 cells. us, the data indicated that BL-1,
BL-2, BL-3, and BL-4 did not appear to have any eects on
cell toxicity and/or cell proliferation in vitro in A549 cells.
DISCUSSION
Substantial experimental evidence has suggested that cell
senescence is dependent on cell division numbers and that the
total cellular life span is measured by the number of cell
generations, not by chronological time.27,28 Telomere erosion is
prevented by the activation of telomerase, a vital enzyme for
tissue regeneration. It has been hypothesized that telomerase is
suppressed during somatic development; hence, the telomere
length shortens with proliferation.3 Further, investigation of fetal
tissues has shown distinct patterns of regulation, with telomerase
activity remaining longer in the liver, lung, and spleen.29
An aging world population has fueled interest in
regenerative remedies that may address declining organ
function and provide solutions to maintain tness. Reducing
or slowing cellular degeneration, which is in part caused by
telomere erosion, is a key factor in addressing aging at the
cellular level. us, the current research team explored the
potential for natural compounds to slow or reverse the process.
Most of the compounds have previously been described
to have some eects on modulating telomerase activity. For
instance, broccoli seeds,30,31 Chlorella vulgaris extracts,32-34
L-carnosine,35 and vitamin D3
36,37 are all known to aect
telomerase activity. In addition, N-acetyl-L-cysteine,38,39
α-lipoic acids,40-42 green tea extract,43-45 chia seeds,46,47 and
French wine extract are known to aect cellular aging, both
by playing a role in free-radical scavenging and by modulating
telomerase. DMAE, known to have antioxidative properties,
is used as an antiaging agent,48,49 whereas rhodiola is used in
traditional Chinese medicine.50-54
Using a PCR-based assay of telomerase activity, the
current study has shown that N-acetyl-L-cysteine, L-carnosine,
rhodiola PE, vitamin D3, chia seeds, broccoli seeds, and
Astragalus extract all increased telomerase activity when
comparing PD-2 with PD-15 and when comparing those
compounds with the control cells, for which the current study
observed the expected eect of reduced telomerase activity
with time. In addition, DMAE L-bitartrate, Chlorella powder,
and glycine neither increased nor decreased the telomerase
activity, suggesting that they were able to preserve the
telomerase activity from PD-2 to PD-15. However, treatment
of cells with α-lipoic acid, green tea extract, and French red
wine extract appeared to have no benecial eect on telomerase
activity, showing a decrease in telomerase activity with time
that was similar to that observed in the control cells.
Aer investigating the telomerase-modulating eects of
all of the single compounds individually, the current research
created 8 proprietary blends, with dierent concentrations
and compositions of the compounds based on their
performance characteristics during the initial evaluation of
telomerase activity. Although it would be feasible simply to
pick the best individual compound, other factors, such as
synergistic eects, cancer proliferation eects, other adverse
events, reliance on a single material source, and future cost
considerations, made it clear that it was important to study
the combined eects of the compounds.
e current study’s data showed that all blends were
capable of increasing telomerase activity, when comparing
PD-2 to PD-15, with dierent levels of activation, ranging
from 51% to 290% relative to the controls.
Figure 7. Eects of BL-1, BL-2, BL-3, and BL-4 on the
Antiproliferative Activity of the Chemotherapeutic Agent
Topotecan, a Topoisomerase I Inhibitor, on A549 cells, With
48 Hours of Treatment
Figure 6. Eects of BL-1, BL-2, BL-3, and BL-4 on the
Cytotoxicity of Topotecan in A549 Cells, With 48 Hours of
Treatment
Note: BL-1, BL-2, BL-3 and BL-4 did not aect topotecan’s
anticancerous activity or toxicity.
Cytotoxicity (% of control)
200
180
160
140
120
100
80
60
40
20
0
Topotecan Dose (μM)
0 0.1 0.5 1 10
Control
BL-1
BL-2
BL-3
BL-4
Proliferation (% of control)
120
100
80
60
40
20
0
Topotecan Dose (μM)
0 0.1 0.5 1 10
Control
BL-1
BL-2
BL-3
BL-4
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
Ait-Ghezala—Telomerase Activation With Natural Compounds ALTERNATIVE THERAPIES, VOL. 22 NO. S2 13
e 4 most potent blends—BL-1, BL-2, BL-3, and
BL-4—all performed better than TA-65, the positive control,
which has been shown to elongate short telomeres and
increase the life span of adult and old mice, without any
increase in cancer incidence.15-20,55 ose 4 blends were
chosen for further investigation with regard to safety (ie, any
eects on cancer proliferation and comparison against
human data on other agents promoting telomerase activity).
In a human, double-blind, 4-month, randomized,
controlled trial,24 treatment with PUFA was shown to increase
telomere length in relation to the decrease in the n-6:n-3
PUFA plasma ratios. Human studies to investigate telomerase
activity and telomere lengthening in humans need to consider
parameters such as sample size and the study’s duration,
which are not well established at the current time because
few such studies have been conducted.
Kiecolt-Glaser et al24 thus have provided important
guidance for the design of future studies because the study
demonstrated changes in telomerase activity and telomere
lengthening its population of 106 individuals in a 4-month
timeframe. In the current study’s in vitro assay, the research
team compared each of 4 blends against the eects of PUFA
combinations. All 4 of the blends outperformed the FA
treatments, which supports their further investigation in
human studies.
Concerns have been voiced as to the potential cancer-
promoting eects of telomerase activators, although to the
current research team’s knowledge, no experimental evidence
exists of such compounds increasing the occurrence of
cancer. Although telomerase does not drive the oncogenic
process, it is permissive and required for the sustained
growth of most advanced cancers. e current study’s tumor
cell proliferation assay provided no evidence for cancer-
promoting eects for its top 4 blends, nor did the blends
interfere with the anticancerous effects of the
chemotherapeutic topotecan.
Although this study has generated important ndings in
the eld of healthy ageing, we are aware of its limitations and
shortcomings. e major limitations herein are listed as
follows: (1) the use of a single cell type, (2) the lack of testing
the eect of the blend of interest beyond PD-15, and (3) the
lack of a companion human study to validate the ndings of
our in vitro experiments. We believe that these limitations
will be addressed and overcome in subsequent work as the
Telomerase Plus blend used in this manuscript is currently
sold as a nutraceutical and can be used in clinical studies to
expand on the existing knowledge of means by which the
ingredients exert their benecial eects.
CONCLUSIONS
e current study’s results have conrmed that many
naturally occurring compounds hold the potential to activate
telomerase and that certain of those compounds have
demonstrated synergistic eects to produce more potent
blends. Given the relationship between telomere shortening,
aging, and the decline of tissue function, it is reasonable to
hypothesize that such telomerase-activating blends may have
health-promoting benets, particularly in relation to aging-
associated conditions. Further investigation of such blends in
human studies that are designed to evaluate safety and the
eects on telomere length are thus warranted.
AUTHOR DISCLOSURE STATEMENT
Funding for the current study was provided by Enzymedica. e Roskamp Institute is
a not-for-prot, public charity, and none of its sta, who comprise all of the authors of
the current paper, received remuneration from Enzymedica. Enzymedica had no role
in the study’s design, data collection or analysis, decision to publish, or preparation of
the manuscript. e authors have declared that no competing interests exist.
REFERENCES
1. Wri g ht W E , S ha y J W. Te lo m er e b io l og y i n a gi n g a nd c a nc er . J Am Geriatr Soc.
2005;53:S292-S294
2. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev
Genet. 2005; 6:611-622.
3. Collins K, Mitchell JR. Telomerase in the human organism. Oncogene.
2002;21:564-579.
4. Greider CW, Blackburn EH. e telomere terminal transferase of Tetrahymena is
a ribonucleoprotein enzyme with two kinds of primer specificity. Cell.
1987;51:887-898.
5. Lingner J, Cooper JP, Cech TR. Telomerase and DNA end replication: No longer
a lagging strand problem? Science. 1995;269:1533-1534.
6. Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88(2):557-579.
7. De Lange T. Shelterin: e protein complex that shapes and safeguards human
telomeres. Genes Dev. 2005;19(18):2100-2110.
8. Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with
idiopathic pulmonary brosis. N Engl J Med. 2007;356:1317-1326.
9. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the
human di sease dyske ratosis conge nita. Nature. 1999; 402:551- 555.
10. Tsakiri KD, Cronkhite JT, Kuan PJ, et al. Adult-onset pulmonary brosis caused
by mutations in telomerase. Proc Natl Acad Sci U S A. 2007;104(18):7552-7557.
11. Vulliamy T, Marrone A, Goldman F, et al. e RNA component of telomerase is
mutated i n autosomal dominant dys keratosis con genita. Nature. 2001;413:432-435.
12. Yamaguchi H, Calado RT, Ly H, et al. Mutations in TERT, the gene for
telomerase reverse transcriptase, in aplastic anemia. N Engl J Med.
2005;352:1413-1424.
13. Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J
Cancer. 1997;33:787-791.
14. Artandi SE, DePinho RA. Telomeres and telomerase in cancer. Carcinogenesis.
2010;31(1):9-18.
15. Bernardes de Jesus B, Blasco MA. Telomerase at the intersection of cancer and
aging. Tren ds G en et . 2013;29(9):513-520.
16. Boscolo-Rizzo P, Rampazzo E, Perissinotto E, et al. Telomere shortening in
mucosa surrounding the tumor: Biosensor of eld cancerization and prognostic
marker of mucosal failure in head and neck squamous cell carcinoma. Oral
Oncol. 2015;51(5):500-507.
17. Meeke r AK, Hi cks JL , Iacob uzio- Donahue C A, et a l. Telome re leng th
abnormalities occur early in the initiation of epithelial carcinogenesis. Clin
Cancer Res. 2004;10(10):3317-3326.
18. Bernardes de Jesus B, Schneeberger K, Vera E, Tejera A, Harley CB, Blasco MA.
e telomerase activator TA-65 elongates short telomeres and increases health
span of adult/old mice without increasing cancer incidence. Aging Cell.
2011;10(4):604-621.
19. Bernardes de Jesus B, Vera E, Schneeberger K, et al. Telomerase gene therapy in
adult and old mice delays aging and increases longevity without increasing
cancer. EMBO Mol Med. 2012;4(8):691-704.
20. Jaskelio M, Muller FL, Paik JH, et al. Telomerase reactivation reverses tissue
degeneration in aged telomerase-decient mice. Nature. 2011;469(7328):102-106.
21. Harley CB, Liu W, Blasco M, Vera E, Andrews WH, Briggs LA, Raaele JM. A
natural product telomerase activator as part of a health maintenance program.
Rejuvenation Res. 2011;14(1):45-56.
22. Harley CB, Liu W, Flom PL, Raaele JM. A natural product telomerase activator
as part of a health maintenance program: Metabolic and cardiovascular response.
Rejuvenation Res. 2013;16(5):386-395.
23. Molgora B, B atem an R, Sweeney G, e t al. Funct ional a sses sment o f
pharmacological telomerase activators in human T cells. Cells. 2013;2(1):57-66.
24. Kiecolt-Glaser JK, Epel ES, Belury MA, et al. Omega-3 fatty acids, oxidative
stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav
Immun. 2013;28:16-24.
25. Huf fman KE, Levene SD, Tesmer VM , Shay JW, Wright W E. Telomere
shortening is proportional to the size of the G-rich telomeric-3’-overhang. J Biol
Chem. 2000;275:19719-19722.
26. Mahoney EM, Hamill AL, Scott WA, Cohn ZA. Response of endocytosis to
altered fatty acyl composition of macrophage phospholipids. PNAS.
1977;74(11):4895-4899.
27. Hayick L. e limited in vitro lifetime of human diploid cell strains. Exp Cell
Res. March 1965;37:614-636.
is article is protected by copyright. To share or copy this article, please visit copyright.com. Use ISSN#1078-6791. To subscribe, visit alternative-therapies.com
28. Shay JW, Wright WE. Hayick, his limit, and cellular ageing. Nat Rev Mol Cell
Biol. 2000;1(1):72-76.
29. Ulaner GA, Giudice LC. De velopmental regulation of telomerase activity in
human fetal tissues during gestation. Mol Hum R eprod. 1997;3(9):769-773.
30. Khan SA, Ahmad A, et al. (2012). Chemistry, fate and chemopreventive actions
of Sulphoraphane. Traditional Medicines 7(6).
31. Mukherjee S, Dey S, Bhattacharya RK, Roy M. Isothiocyanates sensitize the eect
of chemotherapeutic drugs via modulation of protein kinase C and telomerase in
cervical cancer cells. Mol Cell Biochem. 2009;330(1-2):9-22.
32. Makpol S, Yaacob N, Zainuddin A, Yusof YAM, Ngah WZW. Chlorella vulgaris
modulates hydrogen peroxide-induced dna damage and telomere shortening of
human fibroblasts derived from different aged individuals. Afr J Tradit
Complement Altern Med. 2009;6(4):560-572.
33. Makpol S, Yeoh T W, Ruslam FA, Arin KT, Yusof YA. Comparative eect of
Piper betle, Chlorella vulgar is and tocotrienol -rich fraction on antioxidant
enzymes activity in cellular ageing of human diploid fibroblasts. B MC
Complement Altern Med. August 2013;13:210.
34. Saberbaghi T, Abbasian F, Mohd Yusof YA, Makpol S. modulation of cell cycle
prole by Chlorella vulgaris Prevents replicative senescence of human diploid
broblasts. Evid Based Comple ment Al ternat Med. 2013; 2013:780504.
35. Shao L1, Li QH, Tan Z. L-carnosine reduces telomere damage and shortening
rate in cultured normal fibroblasts. Biochem Biophys Res Commun.
2004;324(2):931-936.
36. Pusceddu I, Farrell CJ, Di Pierro AM, Jani E, Herrmann W, Herrmann M. e
role of telomeres and vitamin D in cellular aging and age-related diseases. Clin
Chem Lab Med. 2015;53(11):1661-1678.
37. Ri chard s JB, Valdes AM, Gardner JP, et a l. Hig her s erum vitam in D
concentrations are associated with longer leukocyte telomere length in women.
Am J Clin Nutr . 2007; 86(5):1420-1425.
38. Haendeler J1, Homann J, Diehl JF, et al. Antioxidants inhibit nuclear export of
telomerase reverse transcriptase and delay replicative senescence of endothelial
cells. Circ Res. 2004;94(6):768-775.
39. Liu, J, Liu M, et al. Delay in oocyte aging in mice by the antioxidant N-acetyl-L-
cysteine (NAC). Hu m Rep roduct . 2012; 27(5):1411-1420.
40. Aliev G, Liu J, Shenk JC, et al. Neuronal mitochondrial amelioration by feeding
acetyl-L-carnitine and lipoic acid to aged rats. J Cell Mol Med. 2009;13(2):320-333.
41. Li L, Smith A, Hagen TM, Frei B. Vascular oxidative stress and inammation
increase with age: Ameliorating eects of alpha-lipoic acid supplementation. Ann
N Y Acad Sci. 2010;1203:151-159.
42. Monette JS, Gómez LA, Moreau RF, et al. (R)-α-Lipoic acid treatment restores
ceramide balance in aging rat cardiac mitochondria. Pharmacol Res.
2011;63(1):23-29.
43. Mittal A, Pate MS, et al. EGCG down-regulates telomerase in human breast
carcinoma MCF-7 cells, leading to suppression of cell viability and induction of
apoptosi s. Intern at J Oncol . 2004;24(3):703-710.
44. Sadava D, Whitlock E, et al. e green tea polyphenol, epigallocatechin-3-gallate
inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells.
Biochem Biop hys Res Comm. 2007;360(1):233-237.
45. Yokoyama M, Noguchi M, Nakao Y, Pater A, Iwasaka T. e tea polyphenol,
(-)-epigallocatechin gallate eects on growth, apoptosis, and telomerase activity
in cervical cell lines. Gynecol Oncol. 2004;92(1):197-204.
46. Martínez-Cruz O, Paredes- López O. Phytochemical prole an d nutrac eutical
potential of chia seeds (Salvia Hispanica L.) by ultra-high performance liquid
chromatography. J Chromatogr A. 2014;1346:43-48.
47. Ulbricht C, Chao W, Nummy K, et al. Chia (Salvia hispanica): A systematic
review by the natural standard research collaboration. Rev Recent Clin Trials.
2009;4(3):168-174.
48. Hochschild R. Eect of dimethylaminoethanol on the life span of senile male A-J
mice. Exp Gerontol. 1973;8(4):185-191.
49. Zuckerman BM, Barrett KA. Effects of PCA and DMAE on th e nem atode
Caenorhabditis briggsae. Exp Aging Res. 1978;4(2):133-139.
50. Jafari M, Felgner JS, Bussel II, et al. Rhodiola: A promising anti-aging Chinese
herb. Rejuvenation Res. 2007;10(4):587-602.
51. Schriner SE, Lee K, Truong S, et al. Extension of Drosophila lifespan by Rhodiola
rosea through a mechanism independent from die tary re striction. PLoS One.
2013; 8(5):e63886.
52. Schriner SE, Abrahamyan A, Avanessian A, et al. Decreased mitochondrial
superoxide levels and e nhanced protection against paraquat in Drosophila
melanogaster supplemented with Rhodiola rosea. Free Radic Res .
2009;43(9):836-843.
53. Schr iner SE, Avanesian A, L iu Y, Luesch H, Jafari M. Protection of hum an
cultured cells against oxidative stress by Rhodiola rosea without activation of
antioxidant defenses. Free R adic Biol Me d. 2009;47(5):577-584.
54. Wiegant FA, Surinova S, Ytsma E, Langelaar-Makkinje M, Wikman G, Post JA.
Pla nt adap togen s increas e life span a nd str ess resis tance in C el egans.
Biogerontolog y. 2009;10(1):27-42.
55. Bernardes de Jesus B, Blasco MA. Potential of telomerase activation in extending
health span and longevity. Curr Opin Cell Biol. 2012;24(6):739-743.
According to the National
Institute of Health, more than
30 percent of adults and about
12 percent of children use
health care approaches
developed outside of
mainstream Western, or
conventional, medicine.
A recent survey found
that the use of dietary
supplements is the most popular
complementary health approach.
The most frequently cited
reasons for CAM use are
general wellness, and pain
management.
CAMPractitioner.com
CAM Practitioner:
Where alternative meets mainstream.
There are nearly 4 million articles
in PubMed that respond to the
search medical. But when you
narrow it to complementary
medicine the number of hits drops
to just over 200,000. But even
200,000 are a lot of articles to sift
through. CAM Practitioner is a
new site to help target the most
recent and most heavily
researched topics within PubMed.
CAM Practitioner is a valuable
resource you can use to access
leading research to guide your
practice.
camprac ad.indd 1 6/25/15 11:42 AM
... It was shown that antioxidant and anti-inflammatory agents can be used to slow the loss of telomere length [20]. Furthermore, several studies have reported telomere elongation by androgens such as danazol [7,21] and by herbal products [22][23][24][25][26][27]. ...
... have been shown to exert beneficial effects on telomeres and to stimulate telomerase activity in various models [22,23,31]. Most studies investigated cycloastragenol (TA-65), a single chemical entity isolated by a proprietary purification process from a root extract of Astragalus membranaceus [22,24,25,31,32]. ...
... However, the results concerning telomere elongation after in vivo treatment with danazol have been inconsistent, with substantial variation between patients and evidence of poor tolerance [40]. In addition to androgens, several herbal products have been tested for their effects on telomeres [23,25,26,28]. Cycloastragenol (TA-65), a bioactive compound isolated from Astragalus membranaceus, has been shown to increase telomere length and activate telomerase in both preclinical and clinical studies [22,24,25,31,32,41,42]. ...
Article
Full-text available
A link between telomere shortening and oxidative stress was found in aging people and patients with cancer or inflammatory diseases. Extracts of Astragalus spp. are known to stimulate telomerase activity, thereby compensating telomere shortening. We characterized a multi-component hydroethanolic root extract (HRE) of Astragalus mongholicus Bunge and assessed its effects on telomeres compared to those of danazol. Astragalosides I to IV, flavonoids, amino acids and sugars were detected in the HRE. Samples of peripheral blood lymphocytes with short telomeres from 18 healthy donors (mean age 63.5 years; range 3286 years) were exposed to a single dose of 1 µg/mL HRE or danazol for three days. Telomere length and telomerase expression were then measured. Significant elongation of telomeres associated to a less toxicity was observed in lymphocytes from 13/18 donors following HRE treatment (0.54 kb (0.15–2.06 kb)) and in those from 9/18 donors after danazol treatment (0.95 kb (0.06–2.06 kb)). The rate of cells with short telomeres (<3 kb) decreased in lymphocytes from all donors after exposure to either HRE or danazol, telomere elongation being telomerase-dependent. These findings suggest that the HRE could be used for the management of age-related diseases.
... Few studies have also demonstrated that green tea consumption can affect the cellular telomere length thereby delaying the onset of replicative cellular senescence and improving longevity. Telomere length is argued as a biomarker of longevity [144] and active interest is developing to identify natural augmenters of telomere length or telomerase activity during aging [145]. In this regard, a recent report suggests that consumption of tea stimulant caffeine is associated with increased activity of the enzyme telomerase reverse transcriptase which resulted in the extension of telomere length in the thymus and spleen of caffeine treated mice as opposed to control animals [146]. ...
Article
Full-text available
A cellular senescence-centric understanding of biological aging and age-related chronic diseases is rapidly emerging. As a result, strategies aimed at mitigating the deleterious aspects of cellular senescence are increasingly becoming desirable. Tea is a globally admired and nutrient-rich beverage that not only refreshes the senses but is also implicated in several health beneficial effects including the extension of organismal healthspan and lifespan. The present review discusses the emerging anti-cellular senescence attributes of tea consumption and provides a perspective that the anti-aging aspects of tea should be studied in the purview of cellular senescence. Current understanding of the integrative effects of the immune system and gut microbiome on cellular senescence have also been discussed with the rationale of mitigatory effects of tea. Future research directions and recommendations have been provided which may ultimately help augment tea-oriented successful and healthy aging approaches.
... The G-rich telomeric sequence can assume G-quadruplex DNA secondary structures, able to inhibit telomerase activity. Therefore, inhibition of telomerase or the stabilization of G-quadruplex by natural compounds may represent an important anti-cancer strategy [154,155]. ...
Article
Full-text available
Aging is related to a number of functional and morphological changes leading to progressive decline of the biological functions of an organism. Reactive Oxygen Species (ROS), released by several endogenous and exogenous processes, may cause important oxidative damage to DNA, proteins, and lipids, leading to important cellular dysfunctions. Te imbalance between ROS production and antioxidant defenses brings to oxidative stress conditions and, related to accumulation of ROS, aging-associated diseases. Te purpose of this review is to provide an overview of the most relevant data reported in literature on the natural compounds, mainly phytochemicals, with antioxidant activity and their potential protective efects on age-related diseases such as metabolic syndrome, diabetes, cardiovascular disease, cancer, neurodegenerative disease, and chronic infammation, and possibly lower side efects, when compared to other drugs.
... increased telomere length over a 12-month period while decreases in telomere length were observed with the placebo [5]. Moreover, other studies have also shown that TA-65 increases telomerase activity and increases telomere length [6,7]. The herbal extracts of the root of Astragalus membranaceus and its fractions have not shown any toxicity or genotoxicity [8,9]. ...
Article
Full-text available
Background: Telomerase Activator 65 (TA-65), a compound extracted from Astragalus membranaceus has been used in Chinese traditional medicine for extending life span. Scarce information exists on the effects of TA-65 on parameters of metabolic syndrome (MetS). Methods: We recruited 40 patients with MetS to determine the effects of TA-65 on dyslipidemias, hypertension, and oxidative stress in this at-risk population. The study was a double-blind, randomized crossover design in which patients were allocated to consume either 16 mg daily of a TA-65 supplement or a placebo for 12 weeks. Following a 3-week washout, participants were allocated to the alternate treatment for an additional 12 weeks. Anthropometric and biological markers were measured at the end of each treatment. Plasma lipids, glucose, C-reactive protein (CRP), liver enzymes, and glycosylated hemoglobin were measured using a Cobas c-111. Inflammatory cytokines were measured by Luminex technology and markers of oxidative stress by use of spectroscopy. Results: Compared to the placebo period, HDL cholesterol (HDL-C) was higher while body mass index, waist circumference, and the LDL/HDL ratio were lower (p < 0.05) during TA-65 treatment. In addition, plasma tumor necrosis factor-α (TNF-α) was lower during the TA-65 period (p< 0.05). Positive correlations were observed in changes between the placebo and the TA-65 periods in HDL-C and CRP (r = -0.511, p < 0.01), alanine aminotransferase (r = -0.61, p < 0.001) and TNF-α (r = -0.550, p < 0.001) suggesting that the favorable changes observed in HDL were associated with decreases in inflammation. Conclusion: TA-65 improved key markers of cardiovascular disease risk, which were also associated with reductions in inflammation.
... A number of studies have shown that activating telomerase can maintain telomere length, delay aging, and reverse age tissue degeneration [210,211]. TA-65 increased telomerase activity in a telomere shortening cell model -IMR90 cells [212]. TA-65 can also lengthen the red blood cell telomere lengths and produce higher rates of feather renewal in captive zebra finches [213]. ...
Article
Full-text available
Owing to a dramatic increase in average life expectancy and the Family Planning program of the 1970s - 1990s, China is rapidly becoming an aging society. Therefore, the investigation of healthspan-extending drugs becomes more urgent. Astragalus membranaceus (Huangqi) is a major medicinal herb that has been commonly used in many herbal formulations in the practice of traditional Chinese medicine (TCM) to treat a wide variety of diseases and body disorders, or marketed as life-prolonging extracts for human use in China, for more than 2000 years. The major components of Astragalus membranaceus are polysaccharides, flavonoids, and saponins. Pharmacological research indicates that the extract component of Astragalus membranaceus can increase telomerase activity, and has antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic, antihyperglycemic, hepatoprotective, expectorant, and diuretic effects. A proprietary extract of the dried root of Astragalus membranaceus, called TA-65, was associated with a significant age-reversal effect in the immune system. Our review focuses on the function and the underlying mechanisms of Astragalus membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer effects, based on experimental and clinical studies.
... Behaviour could acutely alter exposure to environmental conditions, or substances (either via foods or environmental toxins) that directly increase or reduce inflammation, oxidative stress or telomerase activity. For example, the toxins in tobacco smoke cause increased inflammation and oxidative stress (25,26), whereas eating a diet high in fresh fruit and vegetables boosts anti-oxidant defences, and some naturally occurring substances in food may boost telomerase activity (27). Furthermore, habitually performing certain behaviours may cause chronic changes in inflammation, oxidative stress or biological stress. ...
Preprint
Full-text available
Individual differences in telomere length are associated with individual differences in behaviour in humans and birds. Within the human epidemiological literature this association is assumed to result from specific behaviour patterns causing changes in telomere dynamics. We argue that selective adoption—the hypothesis that individuals with short telomeres are more likely to adopt specific behaviours—is an alternative worthy of consideration. Selective adoption could occur either because telomere length directly affects behaviour or because behaviour and telomere length are both affected by a third variable, such as exposure to early-life adversity. We present differential predictions of the causation and selective adoption hypotheses and describe how these could be tested with longitudinal data on telomere length. Crucially, if behaviour is causal then it should be associated with differential rates of telomere attrition. Using smoking behaviour as an example, we show that the evidence that smoking accelerates the rate of telomere attrition within individuals is currently weak. We conclude that the selective adoption hypothesis for the association between behaviour and telomere length is both mechanistically plausible and, if anything, more compatible with existing empirical evidence than the hypothesis that behaviour is causal. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.
Article
Full-text available
Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of the feed additive consisting of dimethylglycine sodium salt (trade name: Taminizer D) as a zootechnical additive for chickens for fattening. In 2011, the FEEDAP Panel delivered an opinion on the safety and efficacy of the additive, and subsequently, the additive was authorised in the EU. In 2018, a second scientific assessment was made based on a dossier submitted for the modification of the terms of authorisation of the additive. The additive is authorised as 'dimethylglycine sodium salt with a purity of at least 97%' for chickens for fattening under the category 'zootechnical additives' and functional group 'other zootechnical additives (improvement of zootechnical parameters)'. The evidence provided by the applicant indicated that the additive currently in the market, produced by the two manufacturing routes, complies with the conditions of authorisation. No new evidence was found that would make the FEEDAP Panel reconsidering its previous conclusions in the safety for target species, consumers and environment. The FEEDAP Panel concludes that Taminizer D is not a skin irritant but may be an eye irritant and a skin sensitiser; although uncertainty remains on the presence of formaldehyde, exposure is considered extremely low. There is no need to assess the efficacy of the additive in the context of the renewal of the authorisation.
Article
Introduction Telomerase is an enzyme responsible for regulating the length of telomeres in eukaryote chromosomes. Activation and inhibition of telomerase result in the extension and shortening of telomeres, respectively. The mentioned phenomena are attributed to anti-aging and anticancer mechanisms. Spirulina platensis extract has attracted a great deal of attention, as an anti-aging factor. Methods The regulatory impacts of different extracts of these microalgae on telomerase activity in MCF-7 and HDF cells were investigated using a Telomeric Repeat Amplification Protocol and ELISA, in vitro. Results The methanolic extract of S. platensis increased the telomerase activity by 139% and simultaneously showed high toxicity on the MCF-7 cells (82%) with IC50=0.035 mg/ml. Despite this, the methanolic extract demonstrated an unstable activity of HDF cells. In contrast to the methanolic extract, the aqueous extract of S. platensis toxified the cancer cells at the highest rate of 77% (IC50=0.98 mg/ml); however, it inhibited the telomerase activity of MCF-7 cells up to 52%. Additionally, the aqueous extract acted as an anti-aging factor on the HDF cells through upregulating the telomerase activity by 84% at 0.004 mg/ml. The present research suggests that different extracts of S. platensis behave variously on different cell types. Except the aqueous extract, other extracts of S. platensis are capable of inhibiting MCF-7 cancer cells based on a mechanism different than telomerase inhibition. Conclusion The aqueous extract of S. platensis seems to be a safe alternative for use as an anti-aging factor as well as an anticancer agent.
Article
Modern medical approaches to the therapy of various diseases, including cancer, are based on the use of toxic drugs. The unfavorable side effects of traditional medicine could be counterbalanced by addition of natural bioactive substances to conventional therapy due to their mild action on cells combined with the multitargeted effects. To elucidate the real mechanisms of their biological activity, versatile approaches including a number of “omics” such as genomics, transcriptomics, proteomics, and metabolomics are used. This review highlights inclusion of bioactive natural compounds into the therapy of chronic diseases from the viewpoint of modern omics-based nutritional biochemistry. The recently accumulated data argue for necessity to employ nutrigenetic and nutrimetabolomic analyses to prevent or diminish the risk of chronic diseases.
Article
Full-text available
Aging is a complex biological process characterized by a progressive decline of organ functions leading to an increased risk of age-associated diseases and death. Decades of intensive research have identified a range of molecular and biochemical pathways contributing to aging. However, many aspects regarding the regulation and interplay of these pathways are insufficiently understood. Telomere dysfunction and genomic instability appear to be of critical importance for aging at a cellular level. For example, age-related diseases and premature aging syndromes are frequently associated with telomere shortening. Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. Here we review existing knowledge about the link between telomere biology and cellular aging with a focus on the role of vitamin D. We searched the literature up to November 2014 for human studies, animal models and in vitro experiments that addressed this topic.
Article
Full-text available
Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls) in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.
Article
Full-text available
Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24 h prior to enzymes activity determination. Senescence-associated beta-galactosidase (SA beta-gal) expression was assayed to validate cellular ageing. In cellular ageing of HDFs, catalase and glutathione peroxidase activities were reduced, but SOD activity was heightened during pre-senescence. P. betle exhibited the strongest antioxidant activity by reducing SA beta-gal expression, catalase activities in all age groups, and SOD activity. TRF exhibited a strong antioxidant activity by reducing SA beta-gal expression, and SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD activity in senescent HDFs. P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs.
Article
Full-text available
Short average telomere length is associated with low telomerase activity and certain degenerative diseases. Studies in animals and with human cells confirm a causal mechanism for cell or tissue dysfunction triggered by critically short telomeres, suggesting telomerase activation may be an approach to health maintenance. We previously reported on positive immune remodeling in humans taking a commercial health maintenance program, PattonProtocol-1, composed of TA-65® (a natural product-derived telomerase activator) and other dietary supplements (1). In over a 5 year period and an estimated 7000 person-years of use, no adverse events or effects have been attributed to TA-65 by physicians licensed to sell the product. Here we report on changes in metabolic markers measured at baseline (n=97-107 subjects) and every 3-6 months (n=27-59 subjects) during the first 12 months of study. Rates of change per year from baseline determined by mixed effects ANOVA were -3.72 mg/dL for fasting glucose (p=.02), -1.32 mIU/mL for insulin (p=0.01), -13.2 and -11.8 mg/dL for total- and LDL-cholesterol (p=0.002, p=0.002, respectively), -17.3 and -4.2 mm Hg for systolic and diastolic blood pressure (p=0.007 and 0.001, respectively), and -3.6 umole/L homocysteine (p=0.001). In a subset of individuals with bone mineral density (BMD) measured at baseline and 12 months, density increased 2.0% in the spine (p=0.003). We conclude that in addition to apparent positive immune remodeling, PattonProtocol-1 may improve markers of metabolic, bone and cardiovascular health.
Article
Full-text available
Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR) that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2) proteins, insulin and insulin-like growth factor signaling (IIS), and the target of rapamycin (TOR). In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.
Article
Full-text available
In this study, the effects of Chlorella vulgaris (CV) on replicative senescence of human diploid fibroblasts (HDFs) were investigated. Hot water extract of CV was used to treat HDFs at passages 6, 15, and 30 which represent young, presenescence, and senescence ages, respectively. The level of DNA damage was determined by comet assay while apoptosis and cell cycle profile were determined using FACSCalibur flow cytometer. Our results showed direct correlation between increased levels of damaged DNA and apoptosis with senescence in untreated HDFs (P < 0.05). Cell cycle profile showed increased population of untreated senescent cells that enter G0/G1 phase while the cell population in S phase decreased significantly (P < 0.05). Treatment with CV however caused a significant reduction in the level of damaged DNA and apoptosis in all age groups of HDFs (P < 0.05). Cell cycle analysis showed that treatment with CV increased significantly the percentage of senescent HDFs in S phase and G2/M phases but decreased the population of cells in G0/G1 phase (P < 0.05). In conclusion, hot water extract of Chlorella vulgaris effectively decreased the biomarkers of ageing, indicating its potential as an antiageing compound.
Article
Numerous studies suggest that a high consumption of cruciferous vegetables, especially broccoli and broccoli sprouts, can protect against various forms of cancer. The chemo-preventive actions of these cruciferous vegetables have been attributed to sulphoraphane (SFN), a naturally occurring isothiocyanate which they contain. In humans, glucoraphanin isothiocyanate is hydrolyzed by an enzyme, myrosinase, to yield an active metabolite, SFN. Sulphoraphane has been proven to offer protection against oxidative damage and carcinogens. It is also a potent inducer of phase II detoxification enzymes and an inhibitor of phase I enzymes that are involved in the activation of certain carcinogens in body. It also modulates many cancer-related events including, cell death, cell cycle, angiogenesis, invasion and metastasis, making it a highly promising agent for cancer prevention and treatment. The aim of this brief review is to provide updated information to improve our understanding of the chemistry, synthesis and biosynthesis, metabolism and chemoprevention mechanisms of SFN.
Article
Although cancer and aging have been studied as independent diseases, mounting evidence suggests that cancer is an aging-associated disease and that cancer and aging share many molecular pathways. In particular, recent studies validated telomerase activation as a potential therapeutic target for age-related diseases; in addition, abnormal telomerase expression and telomerase mutations have been associated with many different types of human tumor. Here, we revisit the connection between telomerase and cancer and aging in light of recent findings supporting a role for telomerase not only in telomere elongation, but also in metabolic fitness and Wnt activation. Understanding the physiological impact of telomerase regulation is fundamental given the therapeutic strategies that are being developed that involve telomerase modulation.