1
00:00:09,440 --> 00:00:12,760
Speaker 1: Hey, everyone, welcome to another edition of Wisdom Wednesdays, and

2
00:00:12,800 --> 00:00:16,639
Speaker 1: welcome back to our ongoing journey which is almost complete

3
00:00:17,160 --> 00:00:21,000
Speaker 1: about the hallmarks of aging. So today we're doing eleven

4
00:00:21,040 --> 00:00:23,320
Speaker 1: out of twelve and we're going to talk about macro

5
00:00:23,560 --> 00:00:28,200
Speaker 1: autophogy commonly just referred to as autophogy. That is a

6
00:00:28,440 --> 00:00:34,080
Speaker 1: cellular process that is fundamental to staying biologically young, yet

7
00:00:34,080 --> 00:00:39,640
Speaker 1: it often gets overlooked in aging discussions. And autophogy literally

8
00:00:39,720 --> 00:00:44,159
Speaker 1: means self eating, but in the best possible way, and

9
00:00:44,200 --> 00:00:49,800
Speaker 1: it's basically an internal clean up mechanism by which our

10
00:00:49,840 --> 00:00:56,560
Speaker 1: sales break down and recycle damage proteins and dysfunctional organelles.

11
00:00:56,600 --> 00:00:59,960
Speaker 1: They're like bits bits of the sale, such as mitochon

12
00:01:00,000 --> 00:01:04,959
Speaker 1: and other accumulated metabolic junk. And when this system starts

13
00:01:05,000 --> 00:01:08,200
Speaker 1: to break down, as it does when we age, the

14
00:01:08,319 --> 00:01:14,040
Speaker 1: consequences show up virtually in every organ system in the body.

15
00:01:14,760 --> 00:01:18,400
Speaker 1: So let's explore it in a little bit more depth. Basically,

16
00:01:18,400 --> 00:01:23,399
Speaker 1: autoplogy is a cellular housekeeping process, and it's the mechanism

17
00:01:23,440 --> 00:01:28,880
Speaker 1: by which cells degrade and recycle internal components, helping to

18
00:01:29,080 --> 00:01:35,200
Speaker 1: maintain balance and resilience within cells and specifically in macroautoplogy.

19
00:01:35,360 --> 00:01:36,600
Speaker 2: Parts of the cell.

20
00:01:37,120 --> 00:01:42,800
Speaker 1: As I said earlier, like damage mitochondria, are aggregated proteins.

21
00:01:43,560 --> 00:01:45,959
Speaker 2: What happens is they get wrapped.

22
00:01:45,520 --> 00:01:51,000
Speaker 1: In a membrane to form this compound called an autophagisome,

23
00:01:51,680 --> 00:01:56,000
Speaker 1: and that then infuses with something called a lysisome, and

24
00:01:56,080 --> 00:01:58,440
Speaker 1: the contents then are either.

25
00:01:58,280 --> 00:02:01,160
Speaker 2: Broken down or reuse used and removed.

26
00:02:01,160 --> 00:02:05,440
Speaker 1: And it's basically our body's way of doing recycling. And

27
00:02:05,480 --> 00:02:09,359
Speaker 1: it's very very clever because what it does is it

28
00:02:09,440 --> 00:02:13,920
Speaker 1: actually keeps the energy going in the cell and the

29
00:02:14,040 --> 00:02:19,160
Speaker 1: process is tightly regulated by nutrient sensing pathways like m

30
00:02:19,200 --> 00:02:23,520
Speaker 1: tour which we've talked about before, and MPK or amp

31
00:02:23,800 --> 00:02:27,919
Speaker 1: kiness and when energy is low or our cells are

32
00:02:28,040 --> 00:02:33,360
Speaker 1: under stress, MPK is activated and that inhibits m tour,

33
00:02:34,080 --> 00:02:38,280
Speaker 1: therefore inducing autopogy. So, if you can remember from previous podcasts,

34
00:02:38,919 --> 00:02:45,120
Speaker 1: m tor stimulates growth, AMPK stops that growth and activates

35
00:02:45,120 --> 00:02:48,239
Speaker 1: this autoplogy, and it's basically a way that we can

36
00:02:48,360 --> 00:02:52,240
Speaker 1: survive at a cellular level in times of low energy

37
00:02:52,480 --> 00:02:55,840
Speaker 1: or low stress. And it's a big deal because it

38
00:02:56,080 --> 00:03:01,080
Speaker 1: really is essential for us responding to stress, detoxifying the

39
00:03:01,160 --> 00:03:06,000
Speaker 1: cell and even defending against pathogens. And it is really

40
00:03:06,160 --> 00:03:11,200
Speaker 1: key for protecting our brain, for muscle maintenance, for immune

41
00:03:11,200 --> 00:03:14,360
Speaker 1: system regulation, and for metabolic balance.

42
00:03:14,440 --> 00:03:16,920
Speaker 2: So it's widespread throughout the body.

43
00:03:17,400 --> 00:03:21,400
Speaker 1: And when it declines with age, it is associated with

44
00:03:21,480 --> 00:03:24,840
Speaker 1: a protein build up, and that in the brain contributes

45
00:03:24,880 --> 00:03:27,560
Speaker 1: to Alzheimer's and Parkinson's. You'd have heard me talk about

46
00:03:27,639 --> 00:03:31,400
Speaker 1: TAUL proteins in the brain. It also contributes to immune

47
00:03:31,480 --> 00:03:36,160
Speaker 1: dysfunction when it goes wrong, Waker stress responses reduced the

48
00:03:36,160 --> 00:03:42,480
Speaker 1: ability to remove defective mictochondria and then accelerated organ degeneration.

49
00:03:42,640 --> 00:03:45,000
Speaker 1: So you can see there's a number of mechanisms by

50
00:03:45,040 --> 00:03:49,360
Speaker 1: which it contributes to accelerated aging, and as well as

51
00:03:49,520 --> 00:03:55,560
Speaker 1: affecting neurodegeneration and immune agen it also contributes to liver

52
00:03:55,720 --> 00:04:01,720
Speaker 1: dysfunction because partasites rely heavily on a hoopogy to manage

53
00:04:02,040 --> 00:04:06,640
Speaker 1: what's called lipid overload. And it also contributes to muscle

54
00:04:06,680 --> 00:04:11,200
Speaker 1: loss because damage proteins and mitochondria build up in muscle cells,

55
00:04:11,840 --> 00:04:16,520
Speaker 1: empowering muscle regeneration. And basically, just think of it like

56
00:04:16,560 --> 00:04:19,480
Speaker 1: the janitor of your body, and when the janitor goes

57
00:04:19,520 --> 00:04:24,320
Speaker 1: on strike, the whole building aka, your body starts to suffer.

58
00:04:24,839 --> 00:04:25,919
Speaker 2: So let's talk.

59
00:04:25,760 --> 00:04:30,279
Speaker 1: About ways that we can boost autopogy science backed ways.

60
00:04:30,440 --> 00:04:34,520
Speaker 1: The first one no prices for guessing is exercise. It

61
00:04:34,600 --> 00:04:41,520
Speaker 1: is a natural autopogy enhancer. When we exercise sells sense

62
00:04:41,600 --> 00:04:46,240
Speaker 1: this energy stress because at PAI drops when we're exercising,

63
00:04:46,600 --> 00:04:51,039
Speaker 1: and then amp rises and that activates amp kind is

64
00:04:51,480 --> 00:04:55,760
Speaker 1: leading to mpt or inhibition and autopogy induction. And so

65
00:04:56,040 --> 00:04:59,280
Speaker 1: basically the key mechanisms are as I said, the AMPK

66
00:04:59,440 --> 00:05:04,080
Speaker 1: activiation and inhibiting m tour but then reactive oxygen species production

67
00:05:04,600 --> 00:05:09,240
Speaker 1: that actually signals us to do a cellular cleanup. And

68
00:05:09,279 --> 00:05:12,520
Speaker 1: then mild kinds, which I've talked about before. These magical

69
00:05:12,600 --> 00:05:17,599
Speaker 1: molecules released from muscle. They have systemic anti inflammatory effects.

70
00:05:17,640 --> 00:05:22,000
Speaker 1: So there's a really complicated process that actually goes on.

71
00:05:22,400 --> 00:05:27,560
Speaker 1: And in studies of older mice, exercise actually restored autophagic

72
00:05:27,720 --> 00:05:34,120
Speaker 1: fluss in sorry autophagic flux in muscles, improving strength and regeneration.

73
00:05:34,640 --> 00:05:37,080
Speaker 1: And in the brains of the mice it boosted clearance

74
00:05:37,080 --> 00:05:42,640
Speaker 1: of dysfunctional mitochondria and synaptic proteins, which is key for

75
00:05:42,760 --> 00:05:47,400
Speaker 1: cognitive health. The next thing is fasting and calorie restriction,

76
00:05:47,880 --> 00:05:51,160
Speaker 1: and that kind of acts as a master switch for autopogy.

77
00:05:51,640 --> 00:05:52,120
Speaker 2: Fasting.

78
00:05:52,240 --> 00:05:55,680
Speaker 1: Prolonged fasting is one of the most potent natural ways

79
00:05:55,680 --> 00:06:00,680
Speaker 1: to activate autopogy and the energy deficit active. It's AMPK,

80
00:06:01,040 --> 00:06:07,360
Speaker 1: suppresses m tour and boost suritans and they all drive autophogy.

81
00:06:07,800 --> 00:06:11,719
Speaker 1: And then the key benefits of that is increased lifespan

82
00:06:12,000 --> 00:06:18,680
Speaker 1: in model organisms, protection against neurodegeneration, enhanced intestinal and hemopoetic

83
00:06:18,800 --> 00:06:22,160
Speaker 1: stem cell function, which we talked about last time, and

84
00:06:22,320 --> 00:06:26,000
Speaker 1: short term fasting of twenty four to forty eight hours

85
00:06:26,200 --> 00:06:29,520
Speaker 1: has actually been shown to double stem cell activity in

86
00:06:29,640 --> 00:06:34,360
Speaker 1: the gut and immune system via autoplogy pathways. And then

87
00:06:34,400 --> 00:06:38,680
Speaker 1: if you do a more prolonged fast of three four

88
00:06:38,800 --> 00:06:44,400
Speaker 1: days or more, that enhances mitophagi and that's the clearing

89
00:06:44,440 --> 00:06:49,400
Speaker 1: of damage mitochondria. It also improves metabolic flexibility and has

90
00:06:49,480 --> 00:06:52,240
Speaker 1: rejuvenating effects on the immune system. Quite a lot of

91
00:06:52,240 --> 00:06:55,520
Speaker 1: studies have now shown that this happens in both animals

92
00:06:55,560 --> 00:06:59,599
Speaker 1: and in humans. The third way actually just on the

93
00:06:59,680 --> 00:07:04,599
Speaker 1: fasting thing. If you exercise in the fasted state, it

94
00:07:04,680 --> 00:07:09,480
Speaker 1: also enhances autopogy within muscle cells. Only within muscle cells,

95
00:07:09,760 --> 00:07:12,200
Speaker 1: and that's just like an overnight fast and then going

96
00:07:12,240 --> 00:07:14,680
Speaker 1: and doing some morning exercise, so that can be really

97
00:07:14,840 --> 00:07:18,520
Speaker 1: useful for our muscles. And then the third way, which

98
00:07:18,560 --> 00:07:20,560
Speaker 1: is kind of linked to fasting a little bit, is

99
00:07:20,640 --> 00:07:24,880
Speaker 1: ketones and they actually fuel clean up and resilience inside

100
00:07:24,920 --> 00:07:27,920
Speaker 1: our cells. So when we are fasting or on a

101
00:07:28,000 --> 00:07:31,800
Speaker 1: low carb diet, our body produces ketone bodies such as

102
00:07:31,800 --> 00:07:36,120
Speaker 1: beta hydroxy puryate, and they act as a signaling molecule

103
00:07:36,200 --> 00:07:39,360
Speaker 1: for longevity. And we know just if you take beta

104
00:07:39,400 --> 00:07:45,240
Speaker 1: hydroxy purury it that inhibits what we call his stone deacylases.

105
00:07:45,400 --> 00:07:48,360
Speaker 1: This is a bit of a mouthful podcast, isn't it,

106
00:07:48,680 --> 00:07:52,640
Speaker 1: But when you inhibit those things, it actually increases our topogy,

107
00:07:52,720 --> 00:07:57,080
Speaker 1: gene expression and beta hydroxy butty. It also suppresses inflammation

108
00:07:57,280 --> 00:08:01,680
Speaker 1: and oxidative stress and enhances and over of our mitochondria,

109
00:08:01,840 --> 00:08:05,640
Speaker 1: keeping them healthy. And studies show that ke tonges actually

110
00:08:05,800 --> 00:08:11,960
Speaker 1: mimic calorie restriction and provide neuroprotective effects via enhancement of autopogy.

111
00:08:12,240 --> 00:08:15,200
Speaker 1: And there's now research going on that maybe you don't

112
00:08:15,240 --> 00:08:18,840
Speaker 1: have to fast, you can actually take supplemental key tones

113
00:08:18,880 --> 00:08:22,000
Speaker 1: and get some of these benefits. So let's talk about

114
00:08:22,000 --> 00:08:25,520
Speaker 1: stuff that's on the horizon or that's being tested or

115
00:08:25,720 --> 00:08:29,840
Speaker 1: proven right now around autopogy. One you'll not be surprised

116
00:08:29,840 --> 00:08:32,559
Speaker 1: to hear if you've listened to previous podcast is rapamiacin

117
00:08:33,080 --> 00:08:36,320
Speaker 1: that inhibits m tour C one and that's one of

118
00:08:36,360 --> 00:08:40,720
Speaker 1: the central pathways for suppressing autoplogy because it's.

119
00:08:40,559 --> 00:08:41,480
Speaker 2: A growth pathway.

120
00:08:41,960 --> 00:08:46,360
Speaker 1: Rapimiasin extends lifespan in mice. It's now being studied in dogs.

121
00:08:47,080 --> 00:08:50,280
Speaker 1: Matt Chamberlin is doing a big study on that seeing

122
00:08:50,320 --> 00:08:53,120
Speaker 1: if it can enhance the lifespan of dogs, and I

123
00:08:53,280 --> 00:08:55,760
Speaker 1: think that study is due to be released in the

124
00:08:55,800 --> 00:08:59,160
Speaker 1: next year or so. And it's also being tested rapamasin

125
00:08:59,280 --> 00:09:04,520
Speaker 1: in humans for immune system regeneration or rejuvenation and also

126
00:09:04,920 --> 00:09:09,520
Speaker 1: Alzheimer's and forcycopedia that loss of bone and muscle. And

127
00:09:09,640 --> 00:09:12,680
Speaker 1: we'll just see what happens when those studies are published.

128
00:09:13,040 --> 00:09:14,520
Speaker 1: Then the next one is spermidine.

129
00:09:14,920 --> 00:09:20,320
Speaker 2: So this is a a polyamine if you really interested.

130
00:09:20,400 --> 00:09:24,760
Speaker 1: It's found in wheat, germ soy, and age cheese like

131
00:09:24,840 --> 00:09:28,559
Speaker 1: blue cheese, and it's been shown to boost autophogy and

132
00:09:28,679 --> 00:09:32,280
Speaker 1: actually has cardiovascar and cognitive benefits and animal studies.

133
00:09:32,320 --> 00:09:33,760
Speaker 2: You can buy that as a supplement.

134
00:09:34,760 --> 00:09:38,720
Speaker 1: And then there's resveratrol that's found in red wine. There's

135
00:09:38,760 --> 00:09:43,880
Speaker 1: debit about whether it activates surtins, but it does seem

136
00:09:43,960 --> 00:09:49,000
Speaker 1: to mimic some fasting effects and possibly can enhance mitochondria,

137
00:09:49,080 --> 00:09:54,319
Speaker 1: biogenesis and autophogy. But like I said in previous podcasts,

138
00:09:54,679 --> 00:09:58,800
Speaker 1: it has been proven that it actually doesn't extend lifespan.

139
00:09:59,600 --> 00:10:02,600
Speaker 1: Other things that are being studied at met Foreman, and

140
00:10:02,720 --> 00:10:06,119
Speaker 1: that's a diabetes drug that some people think has longevity potential.

141
00:10:06,440 --> 00:10:10,280
Speaker 1: It's been shown to activate amp kinds and improve metabolic health,

142
00:10:10,920 --> 00:10:15,880
Speaker 1: and people think that it indirectly supports autoplogy. So watch

143
00:10:15,960 --> 00:10:18,840
Speaker 1: this space on met Foreman. And then there's a couple

144
00:10:18,880 --> 00:10:24,000
Speaker 1: of other molecules that are being tested. One is Trehallows

145
00:10:24,320 --> 00:10:27,600
Speaker 1: that's a kind of a sugar molecule that induces autoplogy

146
00:10:27,960 --> 00:10:32,120
Speaker 1: independent of the m to our pathway. And then something

147
00:10:32,280 --> 00:10:36,920
Speaker 1: called another mouthful to finish the podcast, peptides like FOXO

148
00:10:37,160 --> 00:10:40,840
Speaker 1: four d RII. Who the hell comes up with these names?

149
00:10:41,040 --> 00:10:46,520
Speaker 1: This is an experimental agent that induces selective autoplogy in

150
00:10:46,600 --> 00:10:48,920
Speaker 1: these sinescent or zombie sales.

151
00:10:49,559 --> 00:10:50,800
Speaker 2: So in closing.

152
00:10:51,280 --> 00:10:53,920
Speaker 1: Firstly, I promise that next week's the last one mould

153
00:10:53,960 --> 00:10:58,280
Speaker 1: have so many big words. But closing thoughts is that

154
00:10:58,559 --> 00:11:03,840
Speaker 1: when this macrotophagy becomes disabled or doesn't work well, it's

155
00:11:03,960 --> 00:11:08,439
Speaker 1: like a broken recycling plant inside yourselves and without it,

156
00:11:08,800 --> 00:11:12,840
Speaker 1: damage starts to pile up, leading to dysfunction, disease, and

157
00:11:12,960 --> 00:11:16,040
Speaker 1: faster aging. But the good news is that you can

158
00:11:16,120 --> 00:11:22,679
Speaker 1: induce ortophogy naturally through exercise, prolonged fasting, and perhaps a

159
00:11:22,800 --> 00:11:27,040
Speaker 1: kidogenic diet or ketone supplements, And there are some pharmological

160
00:11:27,080 --> 00:11:30,320
Speaker 1: tools that are being tested that seem to have quite

161
00:11:30,400 --> 00:11:31,520
Speaker 1: a bit of promise.

162
00:11:31,840 --> 00:11:33,840
Speaker 2: And with most of the aging.

163
00:11:33,559 --> 00:11:38,760
Speaker 1: Intervention, the best strategy is combining lifestyle and science backed

164
00:11:38,840 --> 00:11:42,400
Speaker 1: tools to actually protect against this decline. So that's it

165
00:11:42,480 --> 00:11:45,800
Speaker 1: for this week. In the next week session, the last one,

166
00:11:45,920 --> 00:11:47,600
Speaker 1: it's going to be my favorite, we're going to talk

167
00:11:47,640 --> 00:11:52,000
Speaker 1: about mitochondrial dysfunction. But until then, you're going to amuse

168
00:11:52,080 --> 00:11:54,560
Speaker 1: yourself by re listening to this podcast to see if

169
00:11:54,559 --> 00:11:56,640
Speaker 1: you can work out what the hell I said.

170
00:11:56,920 --> 00:11:57,800
Speaker 2: Catch you next time,