Youreka Science: Genetics of Aging • iBiology

00:00:14.07 As you've probably noticed, some
00:00:16.17 people develop gray hairs earlier than others.
00:00:19.00 And centenarians tend to run in families.
00:00:22.16 In other words, we don't all age
00:00:26.05 at the same rate. Some of us will grow up to be
00:00:30.24 active 90 year olds, running marathons,
00:00:32.26 and others will have degenerative diseases in our 50s.
00:00:36.23 Some of these genetic features are due
00:00:39.13 to environmental influences, such as
00:00:42.06 diet, stress, and exercise. But
00:00:44.26 can the environment alone explain
00:00:46.22 all of these differences and how quickly
00:00:48.23 we age? The short answer is no.
00:00:51.23 The environment alone cannot explain
00:00:53.25 everything when it comes to aging.
00:00:55.29 Then what else could be contributing?
00:00:58.01 In the early 1990's, the idea that aging
00:01:01.08 could be in our genes was hard to imagine.
00:01:03.27 But Cynthia Kenyon, from the University
00:01:05.25 of California in San Francisco,
00:01:07.17 thought it may be possible.
00:01:09.16 Being a geneticist, she knew that most
00:01:12.12 processes were controlled by genes.
00:01:14.03 So she thought these differences
00:01:16.24 in the rate at which we age might also
00:01:19.14 be genetically controlled.
00:01:22.00 Dr. Kenyon attempted to find the genes responsible
00:01:25.09 for aging in humans. Aging in this case was
00:01:29.07 defined as the organism's life span,
00:01:31.07 as well as the rate at which it experienced
00:01:34.01 physical decline. The idea was that
00:01:36.20 perhaps there is one or a set of genes
00:01:41.00 whose activity controls the rate
00:01:42.15 of aging. Maybe these genes are activators of aging,
00:01:46.07 when they are highly active, for example,
00:01:49.05 aging may take place more quickly.
00:01:51.19 Or perhaps it's the other way around,
00:01:54.05 maybe these genes negatively
00:01:56.11 regulate aging, when they are active
00:01:58.18 aging may take place more slowly.
00:02:01.01 Dr. Kenyon's laboratory used a model organism
00:02:05.12 to find the genes responsible for aging,
00:02:07.09 the worm, C. elegans. C. elegans are small
00:02:11.22 simple organisms with a lifespan of 2-3 weeks.
00:02:15.21 This rapid lifecycle makes the study of aging
00:02:18.17 much more feasible.
00:02:20.18 In order to determine if something is
00:02:23.22 controlled by genes, scientists introduce mutations,
00:02:27.00 or modifications to genes, and examine the response.
00:02:30.13 In this case, scientists randomly made
00:02:34.04 mutations to genes in the C. elegans worm.
00:02:36.15 Specifically, they used a clever technique
00:02:39.27 called, temperature-sensitive mutations.
00:02:42.03 While the worm's DNA always contains the mutation,
00:02:46.17 the protein produced from that DNA behaves normally
00:02:49.27 at lower temperatures, but it does not function
00:02:52.25 correctly when the worms are at higher temperatures.
00:02:55.19 So what the scientists did was grow their
00:02:58.22 worms at a normal temperature of 15C,
00:03:02.07 so the mutations would not take effect,
00:03:04.17 and then after the worms progress
00:03:06.28 through their development, the scientists shifted
00:03:09.17 the worms to a higher temperature of 20C.
00:03:13.15 At this higher temperature, the mutations
00:03:16.21 took effect. They then tracked the lifespan
00:03:19.15 of these worms and found that at the higher
00:03:22.11 temperature, some worms lived twice as long as
00:03:25.10 others. These long-lived worms had mutations in the DAF2
00:03:29.15 gene that caused the DAF2 protein to be
00:03:33.00 non-functional. These mutations doubled their
00:03:36.15 lifespan. The long-lived worms weren't just going
00:03:40.23 in a nursing home and hanging on,
00:03:42.21 they were living longer and healthier.
00:03:44.20 They were still fertile, able to feed properly,
00:03:47.24 and very active. They simply seemed to age
00:03:50.22 more slowly. This was incredible, nothing like it
00:03:55.05 had ever been seen before. The scientist had found
00:03:59.16 a gene, one single gene, that when modified
00:04:03.21 delayed aging. But what is DAF2?
00:04:07.13 And does DAF2 control aging in humans
00:04:10.04 like it does in worms?
00:04:11.11 The DAF2 protein is a receptor that
00:04:14.14 responds to insulin-like signals.
00:04:17.01 When conditions are favorable for the C. elegans
00:04:19.19 worm, like when there's a lot of food around,
00:04:22.21 signals through DAF2 regulate growth,
00:04:24.28 metabolism, and energy storage.
00:04:27.11 When DAF2 is non-functional, the worm
00:04:31.07 doesn't get growth signals and sees the environment
00:04:34.09 as dangerous. In response to these perceived
00:04:37.16 dangerous signals, the C. elegans turn on protective
00:04:40.21 pathways to ensure their cells and DNA remain healthy.
00:04:43.28 Thereby, delaying aging.
00:04:46.09 DAF2 is a conserved gene that is also found
00:04:50.09 in many other species, including mice,
00:04:52.23 flies, and humans. When DAF2 is non-functional,
00:04:57.20 mice and flies live longer as well.
00:05:00.11 In humans, certain populations of Ashkenazi Jews
00:05:05.23 that have many centenarians also have less
00:05:08.21 functional DAF2. This would suggest that
00:05:12.01 DAF2 can also control rates of aging
00:05:14.16 in our species, as well.
00:05:16.03 These findings were published in 1993
00:05:20.08 in Nature, in an article titled,
00:05:23.07 "A C. elegans mutant that lives twice
00:05:25.12 as long as wild-type."
00:05:27.01 Thanks to these genetic experiments,
00:05:29.14 scientists could begin studying the molecular
00:05:31.20 mechanism of aging. Since this research, we have gained
00:05:35.17 insight into the genetics of aging.
00:05:37.18 Why do some of us age more quickly than
00:05:40.13 others? Can we intervene with these pathways
00:05:43.17 to delay or even prevent the effects of aging?
00:05:46.05 These questions and the answers they will continue
00:05:49.22 to generate may be used to identify
00:05:52.23 certain interventions that may delay or slow
00:05:55.18 aging, and increase our healthspan.
00:05:58.15 Our ability to live healthy and active lives
00:06:01.20 for longer.
00:06:03.06 This video has been provided to you by
00:06:07.08 YOUREKA Science and iBiology,
00:06:09.09 bringing the world's best biology to you.

This Talk

Speaker: Youreka Science

Audience:

General Public
Educators of H. School / Intro Undergrad
Student
Educators of Adv. Undergrad / Grad
Researcher
Educators

Recorded: February 2016

Talk Overview

Why do some people age more quickly than others? This video describes pioneering research performed by the biologist Cynthia Kenyon, who hypothesized that genes could control the rate of aging. To figure out which genes regulate aging, scientists in Dr. Kenyon’s lab made mutations in the DNA of a tiny worm called C. elegans and looked to see which mutations caused the worms to live longer, healthier lives. Amazingly, modifying just one gene, called Daf-2, allowed the worms to live twice as long as normal. Daf-2 is a conserved gene found in flies, mice, and humans, so its activity may regulate aging in our species as well.

Speaker Bio

Youreka Science

Florie Mar

Youreka Science was created by Florie Mar, PhD, while she was a cancer researcher at UCSF. While teaching 5th graders about the structure of a cell, Mar realized the importance of incorporating scientific findings into classroom in an easy-to-understand way. From that she started creating whiteboard drawings that explained recent papers in the scientific literature… Continue Reading